Gut Liver
Gut-Liver Axis and Sensing Microbes
Normal
Alcohol acetaldehyde
Intestinal dysbiosis
M ce ll
Inflammatory responses in the body to gut-derived and blood-borne pathogens occur in the liver and spleen, the major organs that remove bacteria and their lipopolysaccharide (LPS) from the bloodstream. Several mechanisms have been identified and proposed in this process that relies on a balance between the barrier functions of the gut and the ‘detoxifying’ capacity of the liver [1, 2]. The role of gut-derived LPS has been identified in various liver diseases [6, 7]. The liver has different mechanisms to ‘detoxify’ gut-derived LPS including host lipases [8] and the lack of this protective mechanism was shown to increase inflammatory responses [9]. There is a positive correlation between liver dysfunction and bacterial translocation [10, 11]. Increased gut permeability and/or LPS levels were also noted in liver disease associated with HIV and HCV infection, cirrhosis and cholestasis of pregnancy [6, 12, 13].
骨骼绑定的命名
骨骼绑定的命名骨骼绑定的命名骨骼绑定的制作心得骨骼绑定的命名：首先确定好骨骼是否使用IK_FK转换，如果有转换的话需要命名成为IK,SK,FK三种骨骼形式。
那么命名遵循以下的命名方式：角色名称_角色骨骼类别_角色骨骼名称_角色骨骼编号角色骨骼绑定名称：模型整体名称：Modeling骨骼名称：Joint控制器名称：Control角色名称_角色骨骼类别_角色骨骼名称_角色骨骼编号_控制器_组编号骨骼或者控制器的组用：角色名称_骨骼名称_骨骼编号_Group编号骨骼IK控制的设置：角色名称_IK_IK部位_控制器_组编号Breastbone 胸骨Tail 尾巴腰部SK：根关节####_Sk_Root脊柱####_SK_Back _A1脊柱####_SK_Back _A2脊柱####_SK_Back _A3脊柱####_SK_Back _A4颈椎####_SK_Chest腰部FK：根关节####_Fk_Root脊柱####_FK_Back _A1脊柱####_FK_Back _A2脊柱####_FK_Back _A3脊柱####_FK_Back _A4颈椎####_FK_Chest腰部IK：根关节####_Ik_Root脊柱####_IK_Back _A1脊柱####_IK_Back _A2脊柱####_IK_Back _A3脊柱####_IK_Back _A4颈椎####_IK_Chest腿部骨骼装配的命名：腿部是左右对称的所以需要以Left和Right来区分Left左Right 右腿部极向量约束Polevector腿部分为:大腿Hip小腿Knee脚踝Ankle脚掌Ball脚趾ToeTipHeel 脚后跟Foot脚Leg总的腿手臂和手指命名：手臂是左右对称的所以需要以Left和Right来区分Left左Right 右palm 手掌Specular锁骨Shoulder大臂ShoulderAdded与大臂从和的骨骼Elbow小臂Wrist手腕WristAdded与手腕从和的骨骼。
gut的用法
1. 取出…的内脏(或肠子)2. 把(城市、房屋等)抢劫一空，(从内部)劫掠(或破坏)：例句: Invaders gutted the city.
侵略者把城中的财物洗劫一空。3. (如用火等)毁坏…的内部；破坏…的主要力量；抽去(书籍等的)主要内容：例句: Fire gutted the building and left only the brick wall standing.
- 基于3个网页
hind gut..后食道
hind gut..后食道
hind gut
后食道
推荐文章 ...
hind 后
hind gut; hind intestine 后肠；后食道
hind leg 后腿 ...
- 基于2个网页
- 基于1个网页
3. 肠疝气
词博科技英语主科技词汇[220501-220600] ...
guttering 开沟法
gut-tie 肠绞窄; 肠疝气
Guttiferae 藤黄科 ...
- 基于6个网页
gut tie..肠扭转
bung hole (酒桶的)封塞孔 ...
- 基于4个网页
gut wire..钢丝切丸
gut wire..钢丝切丸
gut wire
钢丝切丸
集装箱相关 ...
grit 棱角砂
gut wire 钢丝切丸
degreasing 去油脂 ...
Gut's
网球魔童
《网球魔童》（Gut's）[第13集]（推荐！！
- 基于4个网页
gut-tie..肠绞窄 | 肠绞窄 肠疝气 | 肠疝气
EASL Clinical Practice Guidelines on Alcoholic Liver Disease
EASL Clinical Practical Guidelines:Management of AlcoholicLiver DiseaseEuropean Association for the Study of the Liver⇑,IntroductionAlcoholic liver disease(ALD)is the most prevalent cause of advanced liver disease in Europe.However,there has been lim-ited research investment into ALD despite its significant burden on the health of Europeans.This disparity is reflected by the ETOh score–the ratio of the estimated population mortality rate to the number of trials focused on a particular disease.The ETOh score for ALD is358,compared with1.4for hepatitis B,4.9for hepatitis C,and15.2for primary biliary cirrhosis[1].In recent years however,the mechanisms driving disease pro-gression and the natural history of ALD have been better defined and novel targets for therapy have been identified[2].In addition, significant clinical research has produced a clear framework for the evaluation of new therapies in particular in patients with alcoholic steatohepatitis(ASH).ALD is a complex disease,the successful management of which hinges on the integration of all the competences in public health,epidemiology,addiction behavior and alcohol-induced organ injury.Both primary intervention to reduce alcohol abuse and secondary intervention to prevent alcohol-associated mor-bidity and mortality rely on the coordinated action of multidisci-plinary teams established at local,national,and international levels.These guidelines are largely based on the issues raised during the EASL monothematic conference on ALD held in Athens in 2010.The guidelines have three main aims:(1)to provide physi-cians with clinical recommendations;(2)to emphasize the fact that alcohol can cause several liver diseases(steatosis,steatohep-atitis,cirrhosis),all of which may coexist in the same patient;(3) to identify areas of interest for future research,including clinical trials.The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation(GRADE)system[3]. The strength of recommendations thus reflects the quality of underlying evidence.The principles of the GRADE system have been enunciated.The quality of the evidence in these clinical practical guidelines(CPGs)has been classified into one of three levels:high(A),moderate(B)or low(C).The GRADE system offers two grades of recommendation:strong(1)or weak(2) (Table1).The CPGs thus consider the quality of evidence:the higher the quality of evidence,the more likely a strong recom-mendation is warranted;the greater the variability in values and preferences,or the greater the uncertainty,the more likely a weaker recommendation is warranted.Burden of ALDBurden of alcohol-related disease and injuryAlcohol consumption is responsible for3.8%of global mortality and4.6%of disability-adjusted life-years(DALYs)lost due to pre-mature death[4].The attributable burden in Europe,with6.5%of all deaths and11.6%of DALYs attributable to alcohol,is the high-est proportion of total ill health and premature deaths due to alcohol of all WHO regions[4,5].Europe shows particularly large sex differences in burden:the deaths attributable to alcohol being11.0%and 1.8%for men and women,respectively.The young account for a disproportionate amount of this disease bur-den,with an alcohol-associated mortality over10%and25%of female and male youth,respectively[6].Burden of ALD in EuropeThe burden of compensated alcohol cirrhosis among the general population and heavy drinkers is not well known.The develop-ment of non-invasive methods to detect significant liverfibrosis (e.g.,elastography,serum markers)should help in elucidating this issue.A recent study in France indicates that alcohol abuse accounts for up to one third of liverfibrosis cases[7].The best comparative proxy for the burden of ALD is mortality from liver cirrhosis as a whole,although as discussed later this has its lim-itations.Mortality rates from liver cirrhosis vary considerably between European countries[8]with a15-fold variation between the highest and lowest national rates[9].However,Europe is essentially divided into two,with Eastern European states tend-ing to have higher rates than the others[8].Time trends in liver cirrhosis mortality over the past30years show very heterogeneous patterns between countries.AbouthalfJournal of Hepatology2012vol.xxx jxxx–xxxKeywords:Alcoholic liver disease;EASL guidelines;Pathogenesis;Diagnosis;Treatment.Received4April2012;accepted4April2012⇑Correspondence:EASL Office,7rue des Battoirs,CH1205Geneva,Switzerland.Tel.:+41228070360;fax:+41223280724.E-mail address:easloffice@easloffice.eu.Contributors:Chairmen:Philippe Mathurin;Antoine Hadengue;RamonBataller.Clinical Practice Guidelines Members:Giovanni Addolorato;PatriziaBurra;Alastair Burt;Juan Caballeria;Helena Cortez-Pinto;Chris P.Day;Ewan H.Forrest;Antoni Gual;David A.Leon;Anna Lligoña;Peter Jepsen;Sebastian Mueller;Georges-Philippe Pageaux;Tania Roskams;Helmut K.Seitz;Felix Stickel.EASLGoverning Board Representative:Mark Thursz.Reviewers:Sylvie Naveau;TimMorgan;Frederik Nevens.the countries of Europe,including Austria,France,Germany,Italy,Portugal,and Spain as well as two Eastern European countries (Hungary and Romania)have experienced sharp declines in liver cirrhosis mortality [9],whereas the Western countries of Finland,Ireland,and the United Kingdom [10],as well as a larger number of Eastern European countries including Estonia [11],Lithuania,Poland,and Russia have increasing rates.In terms of alcohol-related hospital admissions,for example,parallel to the upward trend in liver cirrhosis mortality,general hospital admissions [12],and admissions to intensive care units with ALD have risen sharply in the United Kingdom [13].Limitations to estimate the burden of ALDThe extent of international variation and trends in ALD is difficult to determine.Mortality data from liver disease is available for most countries,and to this extent liver cirrhosis mortality is fre-quently used as the indicator of choice.However,it is not possi-ble to reliably separate out alcoholic from non-alcoholic cirrhosis mortality.In an undetermined proportion of deaths in which alcohol is the key factor,the certifying doctor may choose not to explicitly mention alcohol on the death certificate [14].The extent of this bias is unknown,but it is likely to vary by country,sex,age,and era.For this reason,emphasis is usually given to analyzing mortality from liver cirrhosis regardless of whether it is specified as alcoholic or not [15].These factors,taken together,mean that at the present time our best estimates about the inter-national variation in the burden of ALD,based on mortality from liver cirrhosis as a whole,need to be interpreted with caution.There is a clear need to perform large-scale epidemiological stud-ies to determine the prevalence of compensated ALD in the gen-eral population and the weight of ALD as a cause of cirrhosis.Types of alcohol and patterns of consumptionEuropean countries vary considerably in terms of per capita alco-hol consumption,predominant beverage type,and the extent to which drinkers imbibe substantial quantities on single occasions (binge drinking)[6].In order to propose a consensual definition,the National Institute of Alcohol Abuse and Alcoholism defines binge drinking episodes as consumption of five or more drinks (male)or four or more drinks (female)in the space of about 2h [16].These differences in type and pattern of consumption tendto fall along an East–West divide [17].While per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries [18],there remains uncertainty about whether these other dimensions of drinking behavior in a popu-lation are related to risk [19,20].There are several aspects to this.Firstly,does beverage type matter above and beyond volume of ethanol consumed [21]?Secondly,does drinking to intoxication (sometimes referred to as binge drinking)confer a particular risk?Thirdly,what is the contribution to the burden of ALD induced by the consumption of substances that may contain hep-atotoxic substances in addition to ethanol [20,22,23]?This latter class of drink includes fruit brandies,which are frequently con-sumed in Hungary,for example [24]as well as home brewed alcohols that are drunk in Russia [25]and other parts of the for-mer Soviet Union [26].Risk threshold of alcohol consumption for liver cirrhosisAn important aspect of public health policy concerning alcohol has been the attempt to establish a safe threshold for consump-tion.This revolves primarily around the extent to which moder-ate alcohol consumption is cardioprotective [27,28].This positive effect of alcohol,if real,can then offset the large array of negative health consequences of even moderate alcohol consumption.For many individual diseases such as liver cirrhosis;however,there is no a priori reason to believe a threshold effect exists,as risk appears to increase steeply with the amount of alcohol con-sumed.In a meta-analysis of daily consumption levels in relation to cirrhosis,patients taking 25g of ethanol a day were at higher risk of cirrhosis than non-drinkers [29].A more recent meta-analysis found increased risks of mortality from liver cirrhosis among men and women drinking 12–24g of ethanol per day [30].Indeed,among women,a significant increase was also seen for those drinking up to 12g/day.These levels of consumption (<25g/day)are appreciably lower than most public health rec-ommendations for overall safe levels of consumption.The human evidence to date therefore suggests that if a threshold exists,it is very low,and may in fact be difficult to detect because of limitations in measuring consumption below 10–12g per day.It should be noted that neither meta-analysis was able to dis-tinguish between the effects of daily consumption from the effects of ‘‘binge’’drinking.To this extent little is known aboutTable 1.Grading of evidence and recommendations (adapted from the GRADEsystem).Clinical practical guidelines2Journal of Hepatology 2012vol.xxx jxxx–xxxthresholds as applied to ‘‘binge’’drinking.Further clinical and experimental studies are required to define the role of ‘‘binge’’in the pathogenesis of ALD and the underlying mechanisms.Finally,risk of cirrhosis is almost certainly related to the length of time over which an individual has drunk regularly and not simply to the usual amount consumed.Conversely,there is some clinical evidence that cessation of drinking at any point in the natural history of the disease reduces the risks of disease progression and occurrence of complications from cirrhosis.Public health implicationsEven though there remain uncertainties about the precise burden of and trends in ALD in Europe,there is no doubt that in many countries it is very substantial and or increasing.While improve-ments in treatment are essential,developing population-based policies to reduce levels of harmful and hazardous consumption are a priority.More broadly,there is increasing recognition of the heavy social,health,and economic burdens imposed by heavy alcohol drinking and the policies to reduce harm caused by alco-hol,need to be urgently implemented [31].Several meta-analyses have evaluated the efficacy and cost efficacy of different policy targeted areas [32].The most cost-effective policies are those that reduce availability of alcohol,either through the pricing policies or the hours and places of sale,as well as implementation of min-imum age purchase laws.Statements(1)Alcohol abuse is a major cause of preventable liver diseaseworldwide.(2)Per capita alcohol consumption is strongly correlated withliver cirrhosis mortality rates across countries.Any evi-dence based policy in Europe need to implement preven-tive measures aimed at reducing alcohol consumption at the population level.(3)The binge drinking pattern is becoming increasingly preva-lent,mainly among young individuals,but its impact on liver disease is unknown.RecommendationsSuggestions for future studies(1)Large epidemiological studies using non-invasive methodsshould establish the prevalence of all forms of alcoholic liver disease in the general population.(2)Studies evaluating the short and long-term impact of bingedrinking in the development and severity of ALD are par-ticularly needed.Management of alcohol abuse and alcohol dependenceA large number of European citizens drink alcohol.Europe has the highest per capita alcohol consumption (11L of pure alcohol per year in population P 15years old).Fifteen percent of Europe-ans (58million citizens)drink excessively (>40g per day in men,and >20g per day in women),with a higher proportion among males and young people.Alcohol abuse and alcohol dependence must be seen as differ-ent forms of the same disorder,as it is recognized in the new DSM-V draft.Alcohol abuse is not recognized as a disorder in the ICD-10,and in fact the WHO uses the terms hazardous and harmful alcohol use instead of alcohol abuse.The term ‘risky drinker’is commonly used to define people who drink excessively.Drinking habits of patients need to be routinely screened in patients with liver diseases,and this must be done with tools that have proven its reliability [16].There is a common trend to measure alcohol intake in grams per day or grams per week.Calculations are usually made counting standard drink units [33].The content of a standard drink may differ from country to country,but in Europe most of the countries have fixed their standard drink unit to an ethanol content of 8–10g.Even though measurements in standard drinks may lose accuracy,they are reliable,save time,and are particularly useful in busy clinical settings.Screening tools to detect alcohol abuse and dependenceQuantity-frequency questionnaires and retrospective diaries (time-line follow back)can be used to calculate patients’drinking habits.The former are usually preferred for their simplicity,but they must include data on both working and weekend days.A good alternative to quantity frequency questionnaires is the use of screening instruments to screen risky drinking and alcohol dependence.There are many tools that have been validated and translated into many languages,but the AUDIT (Alcohol Use Dis-orders Inventory Test)remains the ‘gold standard’.Developed by the WHO in 1982,it has proven to have good sensitivity and specificity in clinical settings across different countries [34].The AUDIT has 10questions that explore consumption (1–3),dependence (4–6),and alcohol related problems (7–10)(Table 2).There are two cut-off points,one for dependence and one for risky drinking.Shorter versions have been developed.The AUDIT C includes just the first three questions of the AUDIT and is reliable for the screening of ‘risky drinking’[35,36].The NIAAA (National Institute of Alcohol Abuse and Alcoholism)rec-ommends using the third question of the AUDIT (How often do you have six or more drinks in one occasion?)as a single screen-ing question,which should be followed by the whole AUDIT in case the answer is rated positive [16].JOURNAL OF HEPATOLOGYJournal of Hepatology 2012vol.xxx j xxx–xxx3Screening of patients with psychiatric disordersAlcoholics have a high psychiatric co-morbidity.In general,pop-ulation surveys of alcoholics show high prevalence of anxiety dis-orders,affective disorders,and schizophrenia [37].Anxiety and affective disorders may be independent or concurrent with alco-hol dependence.Independent disorders will need specific treat-ment,while concurrent disorders may disappear once the patient is weaned off alcohol.Alcoholics have a higher risk of developing other addictions,including nicotine.Alcoholics tend to be heavier smokers and the treatment of nicotine dependence requires more intensive support [38].Alcoholics who are polydrug users are difficult to manage and should be systematically referred to specialized treatment.Data suggest that alcohol dependence appears within 5years before the patient is referred to specialist treatment.Special attention should be paid to the coordination between hepatolo-gists and addiction specialists (psychiatrists,psychologists,and social workers)in order to reduce the gap between the signs of alcohol dependence appearing and referral.Because cigarette smoking and alcohol abuse are synergistic in causing cardiovas-cular diseases and cancer,including HCC,hepatologists are encouraged to promote and assist smoking cessation among patients with ALD [39].Management of alcohol withdrawal syndromeAlcohol withdrawal syndrome (AWS)is a severe medical condi-tion affecting alcohol-dependent patients who suddenly discon-tinue or decrease alcohol consumption.Light or moderate AWS usually develops within 6–24h after the last drink and symptoms may include increase in blood pressure and pulse rate,tremors,hyperreflexia,irritability,anxiety,headache,nausea,and vomit-ing.These symptoms may progress to more severe forms of AWS,characterized by delirium tremens,seizures,coma,cardiac arrest,and death [40].Severity scores for AWS are potentially useful in the management of patients.However,these scores are insufficiently validated at this time,especially in the setting of ALD.Benzodiazepines are considered the ‘gold standard’treat-ment for AWS,given their efficacy to reduce both withdrawal symptoms and the risk of seizures and/or delirium tremens [41,42].Long-acting benzodiazepines (e.g.diazepam,chlordiaz-epoxide)provide more protection against seizures and delirium,but short and intermediate-acting benzodiazepines (e.g.loraze-pam,oxazepam)are safer in elderly patients and those with hepatic dysfunction [43].In Europe,clomethiazole is also used to treat AWS [44].Given the side-effects of benzodiazepines in patients with advanced liver disease and potential for abuse,preliminary research has been conducted to identify new medications for AWS,such as clonidine,atenolol,carbamazepine,valproic acid,gamma-hydroxybutyrate,topiramate,baclofen,gabapentin,and pregabalin [45].Whilst sufficient evidence in favor of their use is lacking,topiramate and baclofen have promise given their potential to be used for AWS first [46,47],and then to prevent relapse.Medical therapy of alcohol dependence in patients with ALDAlcohol abstinence represents a critical goal in patients with ALD since abstinence improves the clinical outcomes of all stages of ALD.In the past,disulfiram was the only drug available forTable 2.AUDIT questionnaire [36].To score the AUDIT questionnaire,sum the scores for each of the 10questions.A total P 8for men up to age 60,or P 4for women,adolescents,or men over age 60is considered a positive screeningtest.Clinical practical guidelines4Journal of Hepatology 2012vol.xxx jxxx–xxxalcoholism.Disulfiram represents an effective alcohol pharmaco-therapy [48];however,disulfiram should be avoided in patients with severe ALD because of possible hepatotoxicity [49].More recently,the growing understanding of the neurobiology of alco-holism has led to the development of effective pharmacologic agents that can complement psychosocial treatments,in particu-lar naltrexone [50]and acamprosate [51].Both naltrexone and acamprosate are approved to treat alcoholism;however,these drugs have not been tested in patients with cirrhosis.The opioid antagonist naltrexone has been intensively evaluated,especially the oral formulation [52].A large trial also showed the efficacy of an intramuscular formulation of naltrexone in alcoholism [53].Given the potential for hepatotoxicity,naltrexone has not been tested in patients with ALD,and its use in this population is not recommended.Acamprosate is a modulator of the glutama-tergic receptor system and a meta-analysis of 24randomized controlled trials confirmed its efficacy as an alcohol pharmaco-therapy [54].Based on some clinical trials,gamma-hydroxybu-tyric acid was approved in some European countries (Italy and Austria)to treat alcoholism,but more research is needed,consid-ering the risk of gamma-hydroxybutyric acid abuse [55].Amongst other compounds,topiramate,ondansetron,and baclofen seem the most promising pharmacotherapies for alco-holism [56].Topiramate is an anticonvulsant medication,which has demonstrated safety and efficacy in reducing heavy drinking [57].There was also a decrease in liver enzyme levels in patients treated with topiramate [58];however,topiramate has not been tested in patients with ALD.The 5-HT3antagonist ondansetron has been shown to reduce drinking,but this effect was limited to ‘early onset’alcoholics [59].Some studies suggest that baclo-fen,a GABA B receptor agonist,increases abstinence rate and pre-vents relapse in alcohol-dependent patients [60].Moreover,to date,baclofen represents the only alcohol pharmacotherapy tested in alcoholics with significant liver disease.Baclofen may represent a promising pharmacotherapy for alcohol-dependent patients with ALD.A clinical trial demonstrated the safety and efficacy of baclofen in promoting alcohol abstinence in alcoholic cirrhotics patients [61],but confirmatory studies in cirrhotic patients are warranted.The effect of brief interventionsBrief interventions are often performed through motivational interviewing [62].Motivational interviewing is a technique,which aims to be both non-judgmental and non-confrontational.Its success depends largely on the presentation of objective feed-back based on information provided by the physician.The tech-nique involves acknowledgement that individuals who attend a counseling session,assessment or prevention program may be at different levels of readiness to change their alcohol consump-tion patterns.The technique attempts to increase a patient’s awareness of the potential problems caused,consequences expe-rienced,and risks faced as a result of patterns of alcohol consump-tion.A meta-analysis found evidence for the positive impact of brief interventions on alcohol consumption and alcohol related morbidity and mortality [62].The most recent Cochrane review shows that brief interventions are effective to reduce drinking by an average of 57g per week in men [63].Evidence is less con-clusive in women and populations under 16years of age.A brief intervention should at least have the components defined in the five As’model:Ask about use,Advice to quit or reduce,Assess willingness,Assist to quit or reduce and Arrange follow-up.When a motivational component is added to brief interven-tions its efficacy improves [64].Essential components of a moti-vational approach are an empathic attitude and a collaborative approach that respects the patients’autonomy and evoques from them ways to reach the goals agreed.RecommendationsSuggestions for futures studies(1)Collaborative studies by multidisciplinary teams com-posed of epidemiologists,addiction specialists,and hepa-tologists are strongly encouraged.(2)The impact of brief interventions on the prognosis ofadvanced ALD should be evaluated.(3)More studies testing anti-craving drugs in the setting ofadvanced ALD are required.Pathogenesis of ALDThe spectrum of ALD includes simple steatosis,alcoholic steato-hepatitis (ASH),progressive fibrosis,cirrhosis,and the develop-ment of hepatocellular cancer (HCC).Although many individuals consuming more than 60g of alcohol per day (e.g.1/2a bottle of wine or more than 1L of beer)developsteatosis,JOURNAL OF HEPATOLOGYJournal of Hepatology 2012vol.xxx j xxx–xxx5only a minority of the patients with steatosis progress to ASH and 10–20%eventually develop cirrhosis [65].Genetic and non-genetic factors modify both the individual susceptibility and the clinical course of ALD [2].The mechanisms of ALD are not completely understood.Most studies have been performed in rodents with chronic alcohol intake (e.g.Tsukamoto-French model or Lieber–DiCarli diet).However,these models basically induce moderate liver disease and non-severe fibrosis or liver damage develops.Few studies have been performed so far in liv-ers from patients with ALD.These translational studies are needed to develop novel targeted therapies for these patients [2].The pathogenesis varies in different stages of the disease.Alcoholic fatty liverThere are four main pathogenic factors:(1)Increased generation of NADH caused by alcohol oxidation,favouring fatty acid and tri-glyceride synthesis,and inhibiting mitochondrial b -oxidation of fatty acids [66].(2)Enhanced hepatic influx of free fatty acids from adipose tissue and of chylomicrons from the intestinal mucosa [66].(3)Ethanol-mediated inhibition of adenosine monophosphate activated kinase (AMPK)activity [67]resulting in increased lipogenesis and decreased lipolysis by inhibiting per-oxisome proliferating-activated receptor a (PPARa)[68]and stimulating sterol regulatory element binding protein 1c (SREBP1c)[69].(4)Damage to mitochondria and microtubules by acetaldehyde,results in a reduction of NADH oxidation and the accumulation of VLDL,respectively [66].Alcoholic steatohepatitisAlcoholic fatty livers can develop parenchymal inflammation (mainly by PMN cells)and hepatocellular damage,a prerequisite for progress to fibrosis and cirrhosis.In cases of severe ASH epi-sodes in patients with an advanced disease,ASH may cause pro-found liver damage,increased resistance to blood flow and it is also associated with a poor prognosis [70].Various factors may contribute to the development of ASH (1)Acetaldehyde-induced toxic effects.It binds to proteins [71]and to DNA [72]resulting in functional alterations and protein adducts,which activate the immune system by forming autoantigens.It also induces mito-chondria damage and impairs glutathione function,leading to oxi-dative stress and apoptosis [73].(2)Reactive oxygen species (ROS)generation and the resulting lipid peroxidation with DNA adduct formation [74].Main sources of ROS include CYP2E1-dependent MEOS,mitochondrial electron transport system of the respiratory chain,NADH-dependent cytochrome reductase,and xanthine oxi-dase [75,76].Moreover,chronic alcohol intake markedly up-regu-lates CYP2E1,which metabolizes ethanol to acetaldehyde and parallels the generation of ROS and hydroxyl–ethyl radicals [77].(3)Pro-inflammatory cytokines.Alcohol metabolites and ROS stimulate signaling pathways such as NF j B,STAT-JAK,and JNK in hepatic resident cells,leading to the local synthesis of inflam-matory mediators such as TNF a and CXC chemokines (e.g.inter-leukin-8),as well as osteopontin [78].Alcohol abuse also results in changes in the colonic microbiota and increased intestinal per-meability,leading to elevated serum levels of lipopolysaccharides [79]that induce inflammatory actions in Kupffer cells via CD14/TLR4[80].The resulting inflammatory milieu in the alcoholic liver leads to PMN infiltration,ROS formation and hepatocellular damage.(4)Impaired ubiquitin–proteasome pathway leading to hepatocellular injury and hepatic inclusions of aggregated cyto-keratins (i.e.Mallory–Denk bodies)[81].Fibrosis progressionPatients with ASH may develop progressive fibrosis [82].In ALD,the fibrotic tissue is typically located in pericentral and perisinu-soidal areas.In advanced stages,collagen bands are evident and bridging fibrosis develops.This condition precedes the develop-ment of regeneration nodules and liver cirrhosis.The cellular and molecular mechanisms of fibrosis in ALD are not completely understood [83].Alcohol metabolites such as acetaldehyde can directly activate hepatic stellate cells (HSC),the main collagen-producing cells in the injured liver.HSC can also be activated paracrinally by damaged hepatocytes,activated Kupffer cells and infiltrating PMN cells.These cells release fibrogenic media-tors such as growth factors (TGF b 1,PDGF),cytokines (leptin,angiotensin II,interleukin-8,and TNF a ),soluble mediators (nitric oxide),and ROS.Importantly,ROS stimulate pro-fibrogenic intra-cellular signaling pathways in HSC including ERK,PI3K/AKT,and JNK [84].They also up-regulate TIMP-1and decrease the actions of metalloproteinases,thereby promoting collagen accumulation.Cells other than HSC can also synthesize collagen in ALD.They include portal fibroblasts and bone-marrow derived cells.Whether other novel mechanisms such as epithelia-to-mesen-chymal transition of hepatocytes also play a role in liver fibrosis is under investigation [85].Suggestions for futures studies(1)Experimental models of severe ALD with hepatocellulardamage and fibrosis are needed.(2)Translational studies with human samples of patients atdifferent stages of ALD are required to identify new thera-peutic targets.(3)Studies assessing liver regeneration in severe ALD shouldbe performed.Risk factors for disease progression in alcoholic liver disease Risk factors for fibrosis progression in ALD have been evaluated in two types of approaches:(1)comparisons of the prevalence of risk factors in patients with and without fibrotic ALD;(2)lon-gitudinal evaluation using sequential histology.Risk factors for fibrosis progression can be thought of as host and environmental or genetic and non-genetic.Non-genetic or environmental factors that potentially modulate the development of ALD include the amount and type of alcoholic beverage,the duration of abuse and patterns of drinking.Gender,ethnicity,coexisting conditions such as metabolic syndrome,iron overload,and infection with chronic hepatitis viruses are important genetic or host factors,respectively (Fig.1).Increasingly,the contribution of host genetic factors to the risk of ALD is being acknowledged.There is a clear dose-relationship between the amount of alco-hol and the likelihood of developing ALD.Alcoholic steatosis can be found in 60%of individuals who drink >60g of alcohol per day and the risk of developing cirrhosis is highest in those with a daily consumption of above 120g of alcohol per day [86,87].However,lower daily amounts of alcohol may also lead to signif-icant liver injury in some individuals.The consumption of >40gClinical practical guidelines6Journal of Hepatology 2012vol.xxx jxxx–xxx。
肠肝轴定义
肠肝轴定义肠肝轴定义肠肝轴（Gut-liver axis）指的是肠道与肝脏之间相互作用的生理通路。
以下是有关肠肝轴的相关定义及理由，并推荐一本相关书籍：定义一：肠肝轴肠肝轴是指肠道和肝脏之间通过肠道黏膜屏障、肠道微生物群、肠道免疫系统、门静脉系统等多个因素相互作用而形成的一种互动通路。
理由：肠肝轴的研究对于理解肝脏疾病的发生发展机制具有重要意义。
肠道和肝脏密切联系，通过肠道微生物、免疫等途径的调控相互影响，对肝脏健康具有重要的调节作用。
定义二：肠道黏膜屏障肠道黏膜屏障是肠道内部与外界环境之间的一个保护屏障，由黏膜上皮细胞和黏膜下层组织构成。
它起到屏障作用，阻止有害物质的通过，同时保护有益菌群和营养物质的吸收。
理由：肠道黏膜屏障对于肠道和肝脏之间的交流至关重要。
维持肠道黏膜屏障的完整性可以预防肠道内毒素和有害物质的通过，减轻肝脏的负担，并保持肠道内良好的微生物平衡。
定义三：肠道微生物群肠道微生物群是指存在于肠道中的各种微生物的总和。
包括细菌、病毒、真菌和寄生虫等多种微生物。
肠道微生物群对于维持肠道健康、调节免疫功能等具有至关重要的作用。
理由：肠道微生物群与肝脏健康密切相关。
它们通过产生有益代谢产物、调节免疫反应等途径影响肝脏功能。
肠道微生物群失调可能导致肝脏疾病的发生，如脂肪肝、肝纤维化等。
书籍推荐：《肠肝轴：肠道与肝脏的奇妙连接》该书由XXX撰写，系统介绍了肠肝轴的相关概念、研究进展和临床应用。
书中探讨了肠道微生物群、肠道黏膜屏障、免疫系统等因素对肝脏健康的影响，分析了肠肝轴的疾病机制，并提供了相应的治疗策略和预防措施。
本书适合对肠肝轴感兴趣的读者阅读，尤其是医学、生物学和营养学领域的专业人士。
以上是关于肠肝轴定义的列举及相关理由的简要介绍，希望对您有所帮助。
如需了解更多细节，建议阅读上述推荐书籍或参考相关研究文献。
定义四：肠道免疫系统肠道免疫系统是指存在于肠道黏膜屏障中的免疫细胞和免疫分子的集合体。
肠道菌群与酒精性肝病
曼！！里！堡型翌塑！！翌！里！塑型！曼望！璺！鱼！Ｙ型：箜！墅．竺
肠道茵群与酒精性肝病
熊燕鹃，罗和生 武汉大学人民医院消化内科 【摘要】 酒精性肝病（ａｌｃｏｈｏｌｉｃ
消化系统疾病湖北省重点实验室，湖北武汉４３００６０
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ｎｅｇａｔｉｖｅ ｂａｃｔｅｒｉａ ｔｈａｔ ｗｉｌｌ ｌｅａｄ ｔｏ ｅｎｄｏｔｏｘｅｍｉａ ａｎｄ ｏｖｅｒａｃｔｉｖｅ ｉｍｍｕｎｅ
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抗生素饮酒所致的肠道菌群改变主要与胃肠
道细菌大量繁殖有关。 抗生素疗法通过控制大肠细菌过度繁殖来改善 ＡＬＤ的预后。但是，此疗法虽可以改善肝功能，长期
万方数据
宣墅痘堂塑壁痘堂銎查兰Ｑ！垒生竺旦筮兰！鲞筮２塑 使用又会引起肠道菌群再次失衡，引发病原菌的增长。 抗生素的具体选择又需要根据药敏实验的结果，这将 要求过多地使用细胞培养。所以，抗生素疗法应该针 对那些引起ＳＩＢＯ的肠道菌群。 目前认为，利福昔明、羟氨苄青霉素、克拉维酸、甲 硝唑、环丙沙星、诺氟沙星和头孢氨苄这几种抗生素， 在对抗革兰氏阴性需氧菌和产芽孢厌氧菌的过度生长 方面，疗效肯定。近期已有研究‘１引表明，利福昔明在 肝性脑病的治疗中同样有着非常重要的作用，且对于 ＡＬＤ的治疗效果可观。利福昔明最大的优点就是它 不被胃肠道吸收，副作用很少，且耐药发生率 极低‘２０’２ ２Ｉ。
ｉｎｃｒｅａｓｅ ｉｎ ｔｈｅ ｐｒｏｐｏｒｔｉｏｎ ｏｆ Ｇｒａｍ—
肠肝轴ppt课件
3. 抑制肝脏炎症细胞释放的炎症介质，减少肝脏炎症 反应，改善常规肝功能，减少脂质过氧化，保护肝 细胞的功能 。
Carmela Loguercio，et al. Gut-Liver Axis: A New Point of Attack to Treat Chronic Liver Damage? AJG . 2002
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动物实验：VSL#3 probiotics改善非酒精性脂肪肝
control
anti-TNF-a
VSL#3 probiotics
Fig. 1. Effect of anti-TNF antibodies and VSL#3 on hepatic histology of ob/ob mice. (A) ob/ob mice were treated with 4 weeks of control diet (B)control diet plus anti-TNF antibodies,or (C) control diet plus VSL#3 probiotics.
gut microbiota is still a “forgetten organ”, which is remain almost unknown
肠道菌群=“被遗忘的器官”
Sarkis K, et al. Nature. 2008
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1肠道菌群与肥胖、糖尿病、胰岛素抵 抗
肠道微生物改变胆汁酸结合模式，调节肝 脏和全身脂代谢。分泌肠肽调节游离脂肪 酸形成、吸收和储存。
3
肠道正常菌群
部位
成分
作用
原籍菌 固有的菌群， 厌氧菌：双歧杆菌、类 构成正常菌 杆菌、酪（丁）酸梭菌 群最里层 （科兴 常乐康。。。）
人体器官英语词汇
人体器官英语词汇由多种组织构成的能行使一(特)定功能的结构单位叫做器官。
器官的组织结构特点跟它的功能相适应。
接下来为大家整理了人体器官英语词汇，希望对你有帮助哦!人体器官英语词汇一：head头throat喉咙，咽喉armpit hair腋毛nipple乳头chest胸部pit胸口navel肚脐abdomen腹部private parts阴部thigh大腿neck脖子shoulder肩back背waist腰hip臀部buttock屁股skull颅骨，头盖骨collarbone锁骨rib肋骨backbone脊骨，脊柱shoulder joint肩关节shoulder blade肩胛骨breastbone胸骨elbow joint肘关节pelvis骨盆kneecap膝盖骨bone骨skeleton骨骼sinew腱muscle肌肉joint关节blood vessel血管vein静脉artery动脉capillary毛细血管nerve神经spinal marrow脊髓brain脑人体器官英语词汇二：respiration呼吸windpipe气管lung肺heart心脏diaphragm隔膜exhale呼出inhale呼入internal organs内脏gullet食管stomach胃liver肝脏large intestine大肠blind gut盲肠vermiform appendix阑尾rectum直肠anus肛门bite咬chew咀嚼knead揉捏swallow咽下digest消化absord吸收discharge排泄excrement粪便kidney肾脏bladder膀胱penis阴茎testicles睾丸scroticles阴囊gall bladder胆囊pancreas胰腺spleen脾duodenum12指肠small intestine小肠。
肠道菌群与原发性胆汁性胆管炎的研究进展
•1324•医学研究生学报2019年12月第32卷第12期J Med Pos仲¢,Vol.32,No.12,December,2019综述肠道菌群与原发性胆汁性胆管炎的研究进展杨柳综述，徐丽红审校［摘要］原发性胆汁性胆管炎(PBC)是一种胆汁淤积性自身免疫性肝病，病程迁延，现部分患者临床治疗效果欠佳。
肠道微生态系统主要由肠黏膜和肠道微生物群构成，与肝在功能、解剖上有着非常紧密的联系,并介肠-肝轴，参与维持机体的多种生理、免疫及代谢功能。
分析肠道菌群与PBC之间的相互关系，或可为临床治疗PBC提供新的治疗思路。
文章主要从肠道菌群失调与疾病的关系、肠道菌群及其代谢物与肝的交互作用、菌群移植在治疗PBC的潜在价值等方面进行综述。
［关键词］原发性胆汁性胆管炎;肠道菌群失调;肠道微生物群;菌群移植［中图分类号］R575.22［文献标志码］A［文章编号］1008-8199(2019)12-1324-05［DOI］10.16571/ki.1008-8199.2019.12.018Research progress of gut microbiota and primary biliary cholangitisYANG Liu1reviewing,XU Li-hong2checking(1.Department of Gastroenterology,the First Affiliated Hospital,Medical College of Shihezi University,Shihezi 832000,Xinjiang,China; 2.Department of Gastroenterology,Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu611130,China)［Abstract］Primary biliary Cholangitis(PBC)is a cholestatic autoimmune liver disease with a prolonged course and poor prognosis.The intestinal micro-ecological system is composed primarily by intestinal mucosa and gut microbiota.The system is closely related to the liver in function and anatomy,mediates the gut-liver axis and participates in maintaining various physiological,immune and metabolic functions o£the body.Analysis of the relationship between the gut microbiota and PBC may provide new treatment ideas for clinical treatment of PBC.This article mainly reviews the relationship between gut microbiota imbalance and disease,the interaction of gut microbiota and its metabolites with the liver,and the potential value of fecal microbiota transplantation in the treatment of PBC.［Key words］primary biliary cholangitis;dysfunctions;gut microbiota;fecal microbiota transplantation0引言原发性胆汁性胆管炎(primary biliary cholangitis,PBC)为胆汁淤积性自身免疫性肝病，好发于中年女性，以汇管区非化脓性炎症和肝内小叶间胆管破坏为典型肝病理组织学改变，血清抗线粒体基金项目：国家自然科学基金(81360076)作者单位=832000石河子，石河子大学医学院第一附属医院消化内科[杨柳(医学硕士研究生)];611130成都，成都中医药大学附属第五人民医院消化内科(徐丽红)通信作者：徐丽红，E-mail：xueli_2006@ 抗体多阳性，慢性病程，终末期可进展为肝硬化⑴。
消化科SCI杂志
消化科SCI杂志1 Gastroenterology Gastroenterology 12.899↑2 Hepatology Hepatology 10.84↓3 Gut Gut 9.357↓4 Journal of Hepatology J Hepatol 7.818↑5 Gastrointestinal Endoscopy Gastrointest Endosc 6.713↓6 American Journal of Gastroenterology Am J Gastroent erol 6.012↓7 Clinical Gastroenterology and Hepatology Clin Gastroenterol Hepatol 5.642↓8 Endoscopy Endoscopy 5.545↓9 Seminars in Liver Disease Semin Liver Dis 5.171↑10 Inflammatory Bowel Diseases Inflamm Bowel Dis 4.643↓11 Nature Clinical Practice Gastroenterology & Hepatology Nat Clin Pract Gastroenterol Hepatol 4.52↓12 Current Opinion in Gastroenterology Curr Opin Gastroenterol 4.331↑13 Neuro-Gastroenterology and Motility Neurogastroenterol Motil 3.568↑14 Journal of Viral Hepatitis J Viral Hepat 3.348↑15 Surgical Endoscopy Surg Endosc 3.307↑16 American Journal of Physiology - Gastrointestinal and Liver Physiology Am J Physiol Gastrointest Liver Physiol 3.258↓17 Liver International Liver Int 2.987↑18 Digestive and Liver Disease Dig L iver Dis 2.972↑19 Journal of Gastroenterology J Gastroenterol 2.909↓20 Gastroenterology Clinics Gastroenterol Clin North Am 2.558↑21 Best Practice & Research Clinical Gastroenterology Best Pract Res Clin Gastroenterol 2.48 ↓22 Journal of Gastrointest inal Surgery J Gastrointest Surg 2.402 ↑23 Journal of Gastroenterology and Hepatology J Gastroenterol Hepatol 2.317 ↑24 Journal of Clinical Gastroenterology J Clin Gastroenterol 2.207 ↓25 Pancreatology Pancreatology 2.195 ↓26 World Journal of Gastr oenterology World J Gastroenterol 2.092 ↑27 Scandinavian Journal of Gastroenterology Scand J Gastroenterol 2.084 ↑28 BMC Gastroenterology BMC Gastroenterol 1.886 ↓29 Digestive Diseases and Sciences Dig Dis Sci 1.838 ↑30 Journal of digestive disease s J Dig Dis 1.791 ↑31 Digestion Digestion 1.77 ↓32 European Journal of Gastroenterology and Hepatology Eur J Gastroenterol Hepatol 1.662 ↓33 Hepatology Research Hepatol Res 1.54 ↓34 Diseases of the Esophagus Dis Esophagus 1.493 ↑35 Digestive Dise ases Dig Dis 1.487 ↑36 Digestive Surgery Dig Surg 1.372 ↑37 Reviews in Gastroenterological Disorders Rev Gastroenterol Disord 1.275 ↓38 Journal of gastrointestinal and liver diseases : JGLD J Gastrointestin Liver Dis 1.265 ↑39 Zeitschrift für Gastr oenterologie Z Gastroenterol 1.188 ↑40 Revista Espanola de Enfermedades Digestivas Rev Esp Enferm Dig 0.994 ↓41 Gastroentérologie Clinique et Biologique Gastroenterol Clin Biol 0.928↓42 Turkish Journal of Gastroenterology Turk J Gastroenterol 0.484↑43 Gastroenterology Nursing Gastroenterol Nurs 0.465↓No.按期刊名称排列 按期刊简称排列 参考中文名称 影响因子降序1 Gastroenterology Gastroenterology 胃肠病学12.591 ↑2 Hepatology Hepatology 肝脏病学11.355 ↑3 Gut Gut 英国胃肠病学会杂志9.766 ↓4 Gastrointestinal Endoscopy Gastrointest Endosc 胃肠内窥镜检查7.367 ↑5 Journal of Hepatology J Hepatol 肝脏病学杂志7.056 ↑6 American Journal of Gastroenterology Am J Gastroenterol 美国胃肠病学杂志6.444 ↑7 Endoscopy 内窥镜检查法 6.091 ↑8 Clinical Gastroenterology and Hepatology Clin Gastroenterol Hepatol 临床肠胃病学与肝脏病学 6.068 ↑9 Seminars in Liver Disease Semin Liver Dis 肝病论文集 5 ↓10 Inflammatory Bowel Diseases Inflamm Bowel Dis 炎性肠道疾病 4.975 ↑11 Nature Clinical Practice Gastroenterology & Hepatology Nat Clin Pract Gastroenterol Hepatol 自然临床诊疗:胃肠病学与肝脏病学 4.55 ↑12 Current Opinion in Gastroenterology Curr Opin Gastroenterol 胃肠病新见 3.877 ↑13 American Journal of Physiology - Gastrointestinal and Liver Physiology Am J Physiol Gastrointest Liver Physiol 美国生理学杂志- 胃肠与肝生理 3.587 ↓14 Neuro-Gastroenterology and Motility Neurogastroenterol Motil 神经胃肠病学与自动力 3.48 ↑15 Journal of Viral Hepatitis J Viral Hepat 病毒性肝炎杂志 3.326 ↑16 Surgical Endoscopy Surg Endosc 外科内窥镜；超声及介入技术 3.231 ↑17 Best Practice & Research Clinical Gastroenterology Best Pract Res Clin Gastroenterol 贝勒临床胃肠病学最佳实践与研究 3.128 ↑18 Journal of Gastroenterology J Gastroenterol 胃肠病学杂志 3.117 ↑19 Pancreatology Pancreatology 胰腺病学 3.043 ↑20 Liver International Liver Int 国际肝杂志 2.908 ↑21 Journal of Clinical Gastroenterology J Clin Gastroenterol 临床胃肠病学杂志 2.775 ↓22 Digestive and Liver Disease Dig Liver Dis 消化疾病与肝病 2.577 ↑23 Journal of Gastrointestinal Surgery J Gastrointest Surg 肠胃外科杂志 2.311 ↑24 Gastroenterology Clinics Gastroenterol Clin North Am 北美临床胃肠病学 2.293 ↓25 Journal of Gastroenterology and Hepatology J Gastroenterol Hepatol 胃肠病学与肝脏病学杂志 2.275 ↑26 BMC Gastroenterology BMC Gastroenterol 生物医学中心：胃肠道 2.136 ↑27 World Journal of Gastroenterology World J Gastroenterol 世界胃肠病学杂志 2.081 ↑28 European Journal of Gastroenterology and Hepatology Eur J Gastroenterol Hepatol 欧洲胃肠病学与肝脏病学杂志 2.08 ↑29 Scandinavian Journal of Gastroenterology Scand J Gastroenterol斯堪的纳维亚胃肠病学杂志斯堪的纳维亚胃肠病学杂志 1.98 ↑30 Digestion Digestion 消化 1.836 ↓31 Digestive Diseases and Sciences Dig Dis Sci 消化道疾病与科学 1.583 ↑32 Hepatology Research Hepatol Res 肝脏病学研究 1.562 ↓33 Diseases of the Esophagus Dis Esophagus 食管疾病 1.404 ↑34 Reviews in Gastroenterological Disorders Rev Gastroenterol Disord 胃肠病学评论 1.293 ↑35 Revista Espanola de Enfermedades Digestivas Rev Esp Enferm Dig 西班牙消化系统疾病杂志 1.263 ↑36 Digestive Surgery Dig Surg 消化道外科学 1.257 ↓37 Digestive Diseases Dig Dis 消化系统疾病 1.092 ↑38 Gastroentérologie Clinique et Biologique Gastroenterol Clin Biol 临床胃肠病学与生物学 1.033 ↑39 Zeitschrift für Gastroenterologie Z Gastroenterol 胃肠病学杂志 0.88 ↓40 Gastroenterology Nursing Gastroenterol Nurs 胃肠病护理 0.538 ↑41 Gastrointestinal Endoscopy Clinics Gastrointest Endosc Clin N Am 北美临床胃肠内窥镜学 0 -42 Liver Transplantation & Surgery Liver Transpl Surg 肝移植与外科手术 0 -43 Japanese Journal of Gastroenterology / Nihon Shokakibyo Gakkai Zasshi Nippon Shokakibyo Gakkai Zasshi 日本胃肠病杂志 0 -44 Indian Journal of Gastroenterology Indian J Gastroenterol 印度胃肠病学杂志 0 -45 Gastroenterología y Hepatología Gastroenterol Hepatol 胃肠病与肝脏病学 0 46 Scandinavian Journal of Gastroenterology - Supplement Scand J Gastroenterol Suppl 斯堪的那维亚胃肠病学-增刊 0 -47 Liver Liver 肝脏 0 -48 International Journal of Pancreatology Int J Pancreatol 国际胰腺学杂志 0 -49 Arquivos de Gastroenterologia Arq Gastroenterol 胃肠病学集刊 0 -50 Renaissance Quarterly Renaiss Q 文艺复兴季刊 0 -51 Romanian Journal of Gastroenterology Rom J Gastroenterol 罗马利亚胃肠病学杂志52 Taehan Kan Hakhoe chi / Korean Journal of Hepatology Taehan Kan Hakhoe Chi 韩国肝脏病学杂志 0 -53 Turkish Journal of Gastroenterology Turk J Gastroenterol 土耳其胃肠病学杂志 054 Chinese Journal of Digestive Diseases Chin J Dig Dis 中国消化疾病杂志 0 -55 Minerva Gastroenterologica e Dietologica Minerva Gastroenterol Dietol 肠胃病学与饮食学 0 -56 Current Treatment Options in Gastroenterology Curr Treat Options Gastroenterol 肠胃病学最新治疗方法 0 -57 Baillieres Clinical Gastroenterology Baillieres Clin Gastroenterol 贝勒临床胃肠学58 Hepatitis Weekly Hepatitis Wkly 肝炎周刊 0 -59 Clinics in Liver Disease Clin Liver Dis 临床肝脏疾病 0 -60 Korean Journal of Gastroenterology / Taehan Sohwagi Hakhoe chi Korean J Gastroenterol 韩国胃肠病学杂志 0 -61 Korean journal of hepatology Korean J Hepatol 韩国肝脏病学杂志 0 -62 Journal of digestive diseases J Dig Dis 消化性疾病杂志 0 -63 Journal of gastrointestinal and liver diseases : JGLD J Gastrointestin Liver Dis 胃肠与肝脏疾病杂志 0 -64 Comparative Hepatology Comp Hepatol 比较肝脏病学 0 -65 Current Gastroenterology Reports Curr Gastroenterol Rep 肠胃病学最新报告 0 -66 Journal of the Pancreas JOP 胰腺疾病杂志 0 -。
膳食纤维对人体的重要性（上）：预防和改善肠道疾病，增强免疫力
膳食纤维对人体的重要性（上）：预防和改善肠道疾病，增强免疫力都说膳食纤维对健康重要，可是你知道膳食纤维有哪些好处吗？今天食与心带你详细了解膳食纤维的好处及原因，探讨膳食纤维有益同时有无风险的问题。
一．膳食纤维种类及其来源膳食纤维，是人体必须的第七大营养元素，一般认为不能被人体胃肠道直接消化，因而无法产生热量，但对于生理健康非常重要。
根据在水中的溶解性和在人体肠道的发酵情况，膳食纤维可分为，可溶性纤维和不可溶性纤维，可发酵纤维和不可发酵纤维。
可溶性膳食纤维主要包括果胶、果聚糖（如菊粉和低聚果糖）、β-葡聚糖、乳糖、人乳低聚糖、低聚半乳糖、海带多糖、棉子糖和水苏糖等，可溶于水，可被肠道细菌发酵产生各种代谢产物，比如短链脂肪酸；不可溶性膳食纤维主要包括纤维素、半纤维素、抗性淀粉和木质素等，不溶于水，但部分可被肠道微生物代谢。
膳食纤维是人体健康必须的营养元素，膳食纤维多寡是评价饮食是否健康的关键指标之一。
但是依赖膳食纤维供养的主要并不是人类本身，而是人类的肠道共生微生物；不同膳食纤维可促进肠道不同细菌生长高纤维饮食可提升肠道健康水平膳食纤维可通过调控肠道微生物的种类及其生长，改善肠道健康和肠脑功能，通过肠-脑轴、肠-肝轴、肠-肾轴、肠-心-肾轴和肠-肺轴等等促进人体身心健康[1, 2]。
二．膳食纤维对人有哪些好处膳食纤维发挥有益作用，一方面是通过膳食纤维本身，一方面是通过膳食纤维的活性代谢产物——短链脂肪酸/SCFAs实现的，主要是三种短链脂肪酸——乙酸、丙酸和丁酸，人体90-95%的短链脂肪酸在大肠产生。
由于人体很多器官细胞表面都有识别短链脂肪酸的游离脂肪酸受体，膳食纤维的影响除了消化道，还可达到全身多个器官[1-25]。
下面，食与心带你简单了解膳食纤维对人体的影响。
膳食纤维通过其代谢产物乙酸、丙酸和丁酸，影响全身健康1) 预防和治疗便秘•人们最早认识的膳食纤维的作用之一，促进胃肠道蠕动，促进粪便成形和排出。
慢性胆汁淤积性肝病患者肠-肝轴功能变化研究进展
∗基金项目:国家自然科学基金资助项目(编号:82170585/ 81970507);广州市科技计划项目(编号:20102010013);广州市医学重点学科建设项目(编号:2021-2023)作者单位:510180广州市第一人民医院广州消化疾病中心/华南理工大学附属第二医院消化内科第一作者:陈慧婷,女,医学硕士,主任医师㊂E-mail:eychen-huiting@通讯作者:周永健,E-mail:eyzhouyongjian@ ㊃专家论坛㊃慢性胆汁淤积性肝病患者肠-肝轴功能变化研究进展∗陈慧婷,周永健㊀㊀ʌ关键词ɔ㊀胆汁淤积性肝病;肠-肝轴;肠道菌群;肠道屏障㊀㊀DOI:10.3969/j.issn.1672-5069.2023.03.001㊀㊀Role of gut-liver axis in patients with chronic cholestatic liver diseases㊀Chen Huiting,Zhou Yongjian.Department of Gastroenterology,Guangzhou Digestive Disease Center,First People's Hospital,School of Medicine,South China University of Technology,Guangzhou510180,Guangdong Province,P.R.China㊀㊀ʌKey wordsɔ㊀Cholestasis liver diseases;Gut-liver axis;Gut microbiota;Gut barrier㊀㊀肝脏是人体最大的代谢器官和解毒中心,能够分解代谢营养物质和毒性物质,阻止有害物质进入循环系统,而肠道是机体防御的最前线,是人体最大的免疫器官㊂肠道与肝脏之间的相互作用即肠-肝轴(gut-liver axis),肠道中的营养成分㊁细菌及其代谢产物等通过门静脉进入肝脏,而肝脏中的物质通过胆道系统排泄入肠道㊂肠道微生物群及其代谢产物㊁肠粘膜屏障㊁细菌移位和胆汁酸代谢是肠-肝轴的关键特征[1]㊂肠道菌群紊乱可导致肠道中有害物质增加,有益物质减少,肠道屏障功能受损,肠道来源的细菌产物和代谢物可暴露于肝脏,通过肝-肠循环诱发肝细胞损伤和肠道炎症的发生,并影响肝脏的正常功能,而肝病的进展又会进一步加重肠道菌群的失调,最终导致肝病加重,形成恶性循环㊂因此,保持肠道的健康稳态,对于维持正常的肝脏功能具有重要的作用㊂胆汁淤积是指免疫㊁遗传㊁环境等因素造成胆汁形成㊁分泌和排泄障碍,胆汁不能正常流入十二指肠而进入血液循环的病理学状态,患者可出现黄疸㊁尿色加深㊁乏力㊁瘙痒等㊂各种原因造成肝脏病变导致胆汁淤积性疾病统称为胆汁淤积性肝病(cholestasis liver diseases),主要包括原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)和原发性胆汁性胆管炎(primary biliary cholangitis, PBC)㊂胆汁淤积性肝病起病隐匿,早期常无明显症状而仅表现为血清碱性磷酸酶(ALP)㊁γ谷氨酰转肽酶(GGT)和免疫球蛋白IgG升高,疾病进展后可出现高胆红素血症,且具有进展为肝纤维化㊁肝硬化㊁肝衰竭,甚至死亡的风险㊂目前,胆汁淤积性肝病的病因仍不清楚,研究表明肠-肝轴的失衡是胆汁淤积性肝病发生和发展的重要因素㊂1㊀肠-肝轴肠道和肝脏通过门静脉㊁胆道系统和体循环进行双向交流(crosstalk),其中肠道菌群对于维持肠-肝轴的稳态至关重要㊂肠道微生物群不仅影响着肠道局部功能,而且对全身免疫系统的成熟和维持㊁物质代谢等均起着非常重要的作用㊂肠道微生物种类繁多,包括细菌㊁古生菌㊁真菌和病毒等㊂肠道细菌主要由厚壁菌㊁拟杆菌㊁放线菌和变形杆菌四个门类的细菌组成㊂肠道微生物群的组成受到宿主内在遗传(如基因型)和外在环境(如饮食㊁运动㊁寒冷暴露㊁感染和抗生素等)等诸多因素的影响㊂肠道微生物群紊乱是包括肝病在内的许多疾病发生的基础,肠道微生物紊乱导致肠道通透性升高和细菌移位,称为病原体相关分子模式(PAMPs)㊂PAMPS在血液循环中识别肝细胞中的免疫受体,进而激活炎症级联反应,进入门静脉循环,导致肝细胞损伤㊁肝纤维化和肝硬化[1]㊂此外,肠道微生物代谢物如胆汁酸的变化会影响肠道和肝脏的生理功能㊂肠内胆汁酸分布的改变可以改变肠法尼醇X受体(FXR)活性和成纤维细胞生长因子(FGF)15/19表达,对胆汁酸体内平衡至关重要[2]㊂反之亦然,肝脏通过胆汁系统和体循环释放胆汁酸和炎症介质,如细胞因子等参与肠道沟通㊂2㊀肠道屏障与细菌移位肠道屏障由单层上皮细胞形成,上皮细胞由肠上皮细胞㊁杯状细胞㊁潘氏细胞㊁Tuft细胞和肠嗜铬细胞等组成㊂肠细胞由连接蛋白紧密连接在一起,并与肠腔中的粘液㊁抗菌肽㊁免疫球蛋白㊁产生短链脂肪酸(SCFAs)的共生菌等协同作用,保护肠道免受病原微生物群的伤害[3]㊂肠道屏障对于维持肠道和宿主内部微生物之间的物理和功能隔离是十分重要的㊂在正常情况下,物质有选择性地通过肠道上皮细胞,而当存在肠道屏障功能障碍时主要表现为肠漏(leaky gut),即肠道通透性增加和细菌移位等㊂受损的肠道屏障使得微生物/代谢产物和PAMPs通过门静脉到达肝脏,并通过激活肝脏枯否细胞㊁肝窦内皮细胞㊁肝星状细胞等,导致炎症级联反应[4]㊂在肝脏疾病,特别是肝硬化患者,可以观察到细菌移位增加是一种受细菌过度生长㊁淋巴组织缺陷㊁免疫系统对微生物和PAMPs的异常反应影响的病理生理发生机制㊂3㊀胆汁酸和肠道微生物群之间的相互作用肠-肝轴的一个重要部分是胆汁酸和肠道微生物群之间的相互作用㊂肠道细菌可以将初级胆汁酸代谢为次级胆汁酸改变胆汁酸的信号特性,维持粘液层和紧密连接的完整性,进而改善肠道屏障[5];反过来,胆汁酸也可以通过胆汁酸受体直接或间接地调节肠道微生物群的组成[6]㊂胆汁酸通过肝脏和肠道中的FXR和膜结合G蛋白受体5(TGR5)传递信号[6]㊂胆固醇合成初级胆汁酸,后者在肝细胞中与牛磺酸或甘氨酸结合后释放到肠道中,吸收脂质和脂溶性维生素,大多数在末端回肠被主动重吸收,少部分(约5%)转化为次级胆汁酸,被被动重吸收或排出㊂初级和次级胆汁酸在小肠和大肠中被重新吸收,并通过门脉血返回肝脏,每天完成4~12次的肠肝循环[7]㊂肠道微生物包括拟杆菌㊁梭菌㊁真杆菌㊁乳酸杆菌和大肠杆菌等菌群产生的胆盐水解酶(BSH)[4,8]和7α-脱羟基酶可促进初级胆汁酸向次级胆汁酸的转化㊂FXR通过调控胆汁酸转运和代谢相关基因的表达,促进胆汁酸的肝肠清除,其活性受胆汁酸调节,间接影响肠道菌群㊂胆汁酸依赖性FXR激活还可防止胆汁淤积大鼠肠道屏障功能障碍和细菌移位㊂FXR激动剂已被证明可以预防胆汁淤积症㊁肝硬化㊁动脉粥样硬化和炎症性肠病(IBD)的炎症反应[7]㊂奥贝胆酸(OCA)是FXR激动剂,可调节胆汁酸稳态㊁脂质代谢㊁糖异生和炎症纤维化过程,抑制内源性胆汁酸合成,使小肠中厚壁菌门的比例增加㊂4㊀肠-肝轴与胆汁淤积性肝病PSC患者常同时伴发IBD㊂在肝移植前进行结肠切除术可以降低供体肝脏PSC复发的风险[9,10]㊂从这些现象可以看出肠道和肝脏之间的联系似乎在PSC中更加明显[11],提示肠-肝轴是PSC发病的重要因素[2]㊂多个队列研究显示,与健康对照组比, PSC患者粪便菌群多样性显著降低,并伴有一些特殊物种的丰度改变[2],即共生细菌的相对丰度降低,潜在致病物种丰度增加,主要表现为韦荣球菌㊁梭状芽孢杆菌㊁链球菌属㊁乳杆菌属和肠球菌属等的丰度增加,而粪杆菌属和粪球菌属的丰度降低[1]㊂一项招募了10例PSC-IBD患者的临床试验表明,粪菌移植(FMT)后患者肠道菌群多样性得到显著改善,其中3例患者血清碱性磷酸酶降低了50%以上[11]㊂另一方面,微生态失衡会导致肠道通透性改变并损伤肝脏㊂肺炎克雷伯菌改变了PSC患者的上皮屏障,导致细菌移位,肝脏T辅助17细胞(Th17)诱导的免疫反应导致的肝损伤与肠道通透性相关[12]㊂此外,也有研究发现PSC和PBC患者肝组织胆管上皮细胞具有异常高浓度的内毒素水平[13]㊂总而言之,以上研究提示肠道通透性增加和细菌移位是PSC病理生理学的关键特征㊂目前,还没有完全阐明肠屏障功能障碍是在疾病发展之前还是之后,但可以推断肠屏障功能障碍和炎症可以作为 恶性循环 的一部分促使疾病进展㊂因此,改善肠屏障功能可能是一个有前途的治疗策略㊂在PBC,肠道菌群㊁肠通透性增加和细菌移位也是重要的发病机制[1]㊂与PSC相似,与健康对照人群比,PBC患者肠道微生物组的特点是细菌α多样性降低,链球菌属㊁乳杆菌属和双歧杆菌属丰度增加,而健康人群则是产丁酸盐的粪杆菌属的丰度增加㊂此外,与熊去氧胆酸(UDCA)治疗应答者相比, UDCA治疗无应答者粪杆菌丰度有所降低[14]㊂上海交通大学马雄团队[15]也评估了UDCA治疗初治PBC患者的肠道菌群,发现血清次级胆汁酸水平与PBC患者肠道中富集的菌属呈正相关,而与健康对照组中富集的菌属呈负相关,表明次级胆汁酸水平可能取决于微生物组的组成㊂此外,他们还发现UDCA显示出可以通过减少嗜血杆菌属(Haemophilus spp)㊁链球菌属(Streptococcus spp)和假单胞菌属(Pseudomonas spp)丰度,增加在健康对照中丰度比较高的拟杆菌属(Bacteroidetes spp)㊁Sutterella spp和Oscillospira spp的丰度,部分恢复肠道微生物组的组成[16]㊂在长期暴露于细菌抗原的情况下,BALB/c小鼠肝组织学特征的发展与PBC相当[17]㊂临床上,PBC患者胃和小肠通透性增加[18]㊂与丙型肝炎患者比,脂磷壁酸(lipoteichoic acid,LTA)作为革兰阳性菌的一种细胞壁成分,在PBC患者的肝组织胆管和血清有所增加[19]㊂PBC 患者血清LPS水平高于健康对照[20]㊂总之,这些发现表明PBC患者肠道屏障功能障碍㊂5㊀靶向肠-肝轴治疗胆汁淤积性肝病的可能策略与展望靶向肠道菌群的治疗措施包括益生菌㊁抗生素和FMT等㊂调节肠-肝轴的进一步治疗策略还包括FXR激动剂,后者可以治疗胆汁酸代谢障碍㊁抑制细菌过度生长㊁改善肠屏障功能和肝组织炎症㊂在治疗PSC方面,小样本PSC-IBD患者使用含4种乳酸菌和2种双歧杆菌属的配方治疗3个月未显示明显的疗效[21]㊂抗生素治疗,如万古霉素和甲硝唑,可降低PSC患者血清碱性磷酸酶和胆红素水平,Mayo PSC风险评分下降,但机制尚不清楚㊂利福昔明治疗对PSC无明显疗效[22],但服用米诺环素超过一年可使碱性磷酸酶水平和Mayo PSC风险评分降低[23]㊂如前所述[11],小样本临床试验提示FMT后PSC患者肠道菌群多样性得到显著改善㊂UDCA被广泛用于治疗PSC,但缺乏对包括死亡在内的长期临床疗效的益处分析㊂治疗PBC的基本方法是促进胆汁酸代谢,而UDCA的一线治疗通过诱导胆汁酸流动,增加胆汁酸排泄㊂除了用于治疗瘙痒症的利福平外,目前暂无关于使用抗生素㊁益生菌或FMT 治疗PBC的明确报道[1]㊂综上所述,针对肠-肝轴在慢性胆汁淤积性肝病病理生理学方面的作用和转化研究以及研发靶向肠-肝轴治疗慢性胆汁淤积性肝病的策略,如功能菌群的分离培养㊁肠道菌群代谢产物的功能鉴定㊁肠屏障模型的体外构建㊁菌群与疾病的因果关系验证㊁临床大样本前瞻性队列研究等,是当前临床科研的前沿命题,值得广大研究工作者进一步关注㊂ʌ参考文献ɔ[1]Blesl A,Stadlbauer V.The gut-liver axis in cholestatic liver disea-ses.Nutrients,2021,13(3):1-33.[2]Yan S,Yin X M.Gut microbiome in liver pathophysiology andcholestatic liver disease.Liver Res,2021,5(3):151-163. [3]Albillos A,De Gottardi A,Rescigno M.The gut-liver axis in liverdisease:Pathophysiological basis for therapy.J Hepatol,2020,72(3):558-577.[4]Tripathi A,Debelius J,Brenner D A,et al.The gut-liver axis andthe intersection with the microbiome.Nat Rev Gastroenterol Hepatol,2018,15(7):397-411.[5]Tilg H,Adolph T E,Trauner M.Gut-liver axis:Pathophysiological concepts and clinical implications.Cell Metab, 2022,34(11):1700-1718.[6]Wahlstrom A.Outside the liver box:The gut microbiota as pivotalmodulator of liver diseases.Biochim Biophys Acta Mol Basis Dis, 2019,1865(5):912-919.[7]Chiang J Y L,Ferrell J M.Bile acid metabolism in liver pathobiolo-gy.Gene Expr,2018,18(2):71-87.[8]Wahlstrom A,Sayin S I,Marschall H U,et al.Intestinal crosstalkbetween bile acids and microbiota and its impact on host metabolism.Cell Metab,2016,24(1):41-50.[9]Alabraba E,Nightingale P,Gunson B,et al.A re-evaluation ofthe risk factors for the recurrence of primary sclerosing cholangitis in liver allografts.Liver Transpl,2009,15(3):330-40. [10]Vera A,Moledina S,Gunson B,et al.Risk factors for recurrenceof primary sclerosing cholangitis of liver ncet,2002, 360(9349):1943-1944.[11]Allegretti J R,Kassam Z,Carrellas M,et al.Fecal microbiota trans-plantation in patients with primary sclerosing cholangitis:a pilot clinical trial.Am J Gastroenterol,2019,114(7):1071-1079. [12]Nakamoto N,Sasaki N,Aoki R,et al.Gut pathobionts underlie in-testinal barrier dysfunction and liver T helper17cell immune re-sponse in primary sclerosing cholangitis.Nat Microbiol,2019,4(3):492-503.[13]Sasatomi K,Noguchi K,Sakisaka S,et al.Abnormal accumulation ofendotoxin in biliary epithelial cells in primary biliary cirrhosis and pri-mary sclerosing cholangitis.J Hepatol,1998,29(3):409-416. [14]Furukawa M,Moriya K,Nakayama J,et al.Gut dysbiosis associat-ed with clinical prognosis of patients with primary biliary cholangitis.Hepatol Res,2020,50(7):840-852. [15]Chen W,Wei Y,Xiong A,et prehensive analysis of serumand fecal bile acid profiles and interaction with gut microbiota in primary biliary cholangitis.Clin Rev Allergy Immunol,2020,58(1):25-38.[16]Tang R,Wei Y,Li Y,et al.Gut microbial profile is altered in pri-mary biliary cholangitis and partially restored after UDCA therapy.Gut,2018,67(3):534-541.[17]Haruta I,Kikuchi K,Hashimoto E,et al.Long-term bacterial ex-posure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial b Invest,2010,90(4): 577-588.[18]Feld J J,Meddings J,Heathcote E J.Abnormal intestinal permeabilityin primary biliary cirrhosis.Dig Dis Sci,2006,51(9):1607-1613.[19]Haruta I,Hashimoto E,Kato Y,et al.Lipoteichoic acid may affectthe pathogenesis of bile duct damage in primary biliary cirrhosis.Autoimmunity,2006,39(2):129-135.[20]Zhao J,Zhao S,Zhou G,et al.Altered biliary epithelial cell andmonocyte responses to lipopolysaccharide as a TLR ligand in patients with primary biliary cirrhosis.Scand J Gastroenterol,2011,46(4):485-494.[21]Vleggaar F P,Monkelbaan J F,Van Erpecum K J.Probiotics inprimary sclerosing cholangitis:a randomized placebo-controlled crossover pilot study.Eur J Gastroenterol Hepatol,2008,20(7): 688-692.[22]Tabibian J H,Gossard A,El-Youssef M,et al.Prospectiveclinical trial of rifaximin therapy for patients with primary sclerosing cholangitis.Am J Ther,2017,24(1):e56-e63. [23]Silveira M G,Torok N J,Gossard A A,et al.Minocycline in thetreatment of patients with primary sclerosing cholangitis:results of a pilot study.Am J Gastroenterol,2009,104(1):83-88.(收稿:2023-02-14)(本文编辑:陈从新)。
基于“肠–肝”轴探讨肝脾同调论治酒精性肝病
Advances in Clinical Medicine 临床医学进展, 2023, 13(10), 15970-15976Published Online October 2023 in Hans. https:///journal/acmhttps:///10.12677/acm.2023.13102232基于“肠–肝”轴探讨肝脾同调论治酒精性肝病张毓航黑龙江中医药大学研究生院，黑龙江哈尔滨收稿日期：2023年9月13日；录用日期：2023年10月8日；发布日期：2023年10月13日摘要酒精性肝病(Alcoholic liver disease, ALD)是我国的常见疾病，其发病率逐年上升，对人体健康构成严重威胁。
“肠–肝”轴理论认为，肠道与肝之间复杂的相互作用影响了ALD的发生及发展，这与中医肝脾同治的理论内涵十分相似。
本文分析了“肠–肝”轴与ALD和中医肝脾理论的联系，并结合中药复方探讨肝脾同调论治ALD，以期为临床治疗ALD提供理论基础，为中药研发提供新的思路。
关键词“肠–肝”轴，酒精性肝病，肝脾同治Discussion on the Treatment of AlcoholicLiver Disease with Treating Both Liverand Spleen Based on the Theoryof “Gut-Liver” AxisYuhang ZhangGraduate School of Heilongjiang University of Chinese Medicine, Harbin HeilongjiangReceived: Sep. 13th, 2023; accepted: Oct. 8th, 2023; published: Oct. 13th, 2023AbstractAlcoholic liver disease (ALD) is a common disease in China, the incidence of which is increasing year by year, posing a serious threat to human health. According to the theory of “Gut-liver” axis,张毓航the complex interaction between the gut and liver affects the occurrence and development of ALD, which is quite similar to the connotation of the theory of liver and spleen related to traditional Chinese medicine. This study analyzed the connection between the theory of “Gut-liver” axis and ALD and the link between the theory of “Gut-liver” axis and the theory of liver and spleen related to traditional Chinese medicine, and discussed the treatment of ALD with Chinese medicine com-pound based on the theory of treating both liver and spleen, in order to provide a theoretical basis for the clinical treatment of ALD and offer a new thinking for the research and development of traditional Chinese medicine.Keywords“Gut-Liver” Axis, Alcoholic Liver Disease, Treating Both Liver and SpleenThis work is licensed under the Creative Commons Attribution International License (CC BY 4.0)./licenses/by/4.0/1. 引言ALD是指长期摄入过量酒精而导致肝脏损伤而产生的疾病。
A microbialmetabolitethe gut-liver axissurger(PPT)
1.微生物诱导CA7S和GLP-1的产生
肠道微生物参与 CA7S和GLP-1的产生
The levels of CA7S in the antibiotic-treated and GF mouse intestines were 100- to 200-fold lower than the CA7S levels in fully colonized mice (Figure1D). CA7S levels were undetectable in the livers of antibiotic-treated and GF mice (Figure 1E).
2.微生物诱导哺乳动物肝脏产生CA7S
合成
CA 肠道微生物
CA7S
分解
肠道微生物
TCA7S
2.微生物诱导哺乳动物肝脏产生CA7S
Consistent with previous reports, we did not observe CA7S synthesis by sham or SG cecal bacteria following incubation for 7 days (Figure S1B).
而另外还有2.13亿儿童和青少年和13亿成年人处于超重状态。肥胖会导致心脏负
荷会增加，引起血脂异常，增加脑血管病变，增加高血压，脂肪肝，糖尿病，骨
关节疾病等疾病发生率。袖状胃切除术（SG）是美国最常见的减肥手术。
袖状胃切除术（SG）
袖状胃切除术，又称缩胃手术，它利用腹腔镜技术将胃大弯一侧切掉， 仅留下胃小弯侧一条管状的通道，主要用于减重和2型糖尿病的治疗。临床 研究已经确定了手术后持续发生的三大变化：（1）循环肠促胰岛素GLP-1水 平升高；（2）胆汁酸（BA）库的变化；（3）肠道微生物组分的变化，改变 胃肠激素，重塑糖脂代谢，从而达到减重降糖的效果。
肝性脑病英
• Principle inhibitory neurotransmitters • Generated in the gut by bacteria
• s the diseased or shunted liver
γ- Aminobutyric acid hypothesis
• GABA-receptor complex: Localized to postsynaptic membranes Key contributor to neuronal inhibition in HE • GABA-ergic: 25% ~ 65% of nerve endings • Increased blood-brain barrier permeability • Increased number of binding sites
Sedative Benzodiazepines Hypoxia Hypoglycemia Hypothyroidism Anemia
Pathogenesis (1)
• Toxic materials derived from nitrogeneous substrate in the gut and bypass the liver
Ammonia neurotoxicity
• Ammonia production
resulting from the degradation of urea or protein primary site: gut other site: kidney and skeletal muscles Gut-generating ammonia: 4g/day Equilibrium of ammonia and ammonium:
韩国-IL-28B
Gut and Liver, Vol. 8, No. 1, January 2014, pp. 70-78Role of Interleukin-28B Genetic Polymorphisms in Korean Patients with Hepatitis C Virus InfectionHo Kil*, Sook-Hyang Jeong*, Jin-Wook Kim*, Young Sang Byoun*, Bo Young Min*, Byung-Hyun Woo*, Youn Jae Lee †, and Young Seok Kim ‡*Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, †Department of Internal Medicine, Inje University Busan Baik Hospital, Inje University College of Medicine, Busan, and ‡Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, KoreaBackground/Aims: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B ) gene with respect to clinical outcomes and the anti -viral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. Methods: Two SNPs near IL28B , rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. Results: The CC genotype frequency was significantly higher in the spontaneous recov -ery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predic -tor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic re -sponses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. Conclusions: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea. (Gut Liver 2014;8:70-78)Key Words: Hepatitis C; Interleukin-28B; Recovery; Treat -ment; KoreaCorrespondence to: Sook-Hyang JeongDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, KoreaTel: +82-31-787-7034, Fax: +82-31-787-4052, E-mail: jsh@Received on March 13, 2013. Revised on April 27, 2013. Accepted on May 22, 2013. Published online on November 5, 2013.INTRODUCTIONAbout 130 to 170 million people were infected with hepatitis C virus (HCV) worldwide.1 Globally, 27% of liver cirrhosis (LC) and 25% of hepatocellular carcinoma (HCC) were attributable to HCV.2 About 50% to 80% of patients with HCV infection prog-ress to chronic infection which can lead to LC or HCC.3 Standard treatment for hepatitis C infection is a combination therapy with pegylated-interferon a and ribavirin but currently new standard care was suggested with triple combination therapy includ-ing direct antiviral agents (i.e., boceprevir or telaprevir) aiming to achieve sustained virologic response (SVR).4,5 Interestingly, compared to Caucasian patients, Asian patients showed higher rate of spontaneous clearance of HCV in acute hepatitis C,6 and higher SVR rate after antiviral therapy in chronic hepatitis C,7 although the mechanism of this phenomenon was unclear.Recently, several genome wide association studies (GWAS) showed that single nucleotide polymorphism (SNP) near inter-leukin-28B (IL28B ) gene is associated with SVR rate in HCV genotype 1 infection regardless of different ethnic group.8-11 Especially in the treatment naïve patients, IL28B genotype is related to the response in patients receiving triple therapy.12 Therefore, several centers adapt the genotyping of IL28B SNP to predict SVR before antiviral therapy and to minimize useless treatment. Although one of the GWAS was reported in Japan, there were not enough studies on the role of IL28B polymor-phism in the clinical outcomes or SVR in the Asian patients including Koreans. The objectives of this study were to investi-gate the association between IL28B SNP and clinical outcomes of HCV infection, to evaluate the association between IL28B SNP and SVR in genotype 1 infection, and to suggest the prac-Kil H, et al: IL28B SNP in Korea 71tical utility of IL28B genotyping under the current strategy of response-guided therapy (RGT).MATERIALS AND METHODS1. PatientsStudy subjects are comprised of the two groups: 147 health check examinees enrolled in Seoul National University Bun-dang Hospital, and 307 patients infected with HCV who were retrospectively enrolled in three university hospitals from Janu-ary 2007 to December 2010. The health check examinees were selected after matching age and sex distribution to the standard Korean population according to the census for Korean popula-tion in 2007, so that they were a surrogate group of general population. Among the 307 patients with HCV infection, 47 patients were spontaneously recovered from acute infection without antiviral therapy showing a positive result for anti-HCV and repeatedly negative results for HCV RNA at least two times with normal liver function tests (spontaneous recovery group). The chronic infection group included 260 patients showing a positive serum HCV RNA for more than 6 months, which were classified into chronic hepatitis group (174 patients), LC group (53 patients), and HCC group (33 patients). LC was diagnosed according to the compatible biopsy findings, or clinical findings such as varices, ascites, and compatible radiologic findings. HCC was diagnosed according to the criteria suggested in American Association for the Study of Liver Diseases guideline.13 Exclu-sion criteria were as follows: 1) age less than 18 years; 2) coin-fection with chronic hepatitis B or human immunodeficiency virus.In the chronic infection group, 151 patients (58%) were in-fected by genotype 1 HCV (mostly genotype 1b) and 109 pa-tients (42%) by genotype 2 (mostly genotype 2a). In the geno-type 1 HCV-infected 151 patients, 70 patients were treated and evaluable on the achievement of SVR. Among the 70 patients, 55 patients had complete results on the rapid virologic response (RVR), early virologic response (EVR), and SVR.2. Response-guided standard antiviral therapy Pegylated interferon a-2a (180 µg, Pegasys®; Roche, Basel, Switzerland) or pegylated interferon a-2b (1.5 µg/kg, Pegin-tron®; MSD, Whitehouse Station, NJ, USA) was injected subcu-taneously once a week and ribavirin (Viramid®; Ilsung Pharma-ceuticals Co., Seoul, Korea) was administered orally twice daily at a dose of 1,000 to 1,200 mg/day for 48 weeks in genotype 1 patients; 800 mg/day for 24 weeks in genotype 2 patients. RVR was defined as a negative serum HCV RNA at 4 weeks of treatment. EVR was defined as ≥2 log10 reduction in serum HCV RNA level at 12 weeks of therapy, and SVR was defined as undetectable serum HCV RNA at 6 months after completion of therapy.3. Laboratory evaluationAll patients tested positive for serum anti-HCV antibodies (ADVIA centaur® XP assay; Bayer Healthcare LLC, Tarrytown, NY, USA). The HCV RNA was amplified using RNA polymerase chain reaction (PCR) and hybridization methods (lower limit of detection 50 IU/mL, COBAS® Amplicor HCV test version 2.0; Roche Molecular Systems, Branchburg, NJ, USA), and the serum concentration of HCV RNA was measured using real-time PCR (COBAS® AmpliPrep/COBAS® TaqMan® HCV Test; Roche Mo-lecular Systems).4. Genotypic analysis of IL28B SNPGenomic DNA was isolated from peripheral blood leuko-cytes using the DNA purification kit. Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using a TaqMan 5’ allelic discrimination assay. PCR reactions were carried out in a total volume of 25 µL with the following amplification protocol: preincubation at 60o C for 1 minute and at 95o C for 10 minutes, followed by 40 cycles of 95o C for 15 seconds and 60o C for 1 minute. The PCR results and genotype of each sample were automatically attributed by the SDS 2.2.1 software for allelic discrimination (Applied Biosystems, Foster City, CA, USA).5. Statistical analysisThe differences in numeric variables and categorical variables were tested with Student t-test and with chi-square tests or Fisher exact tests as appropriate. The multivariate logistic re-gression analysis was planned using variables showing p-value of less than 0.10 in the univariate analysis. Statistical analysis was conducted using PASW statistics 18.0 (SPSS Inc., Chicago, IL, USA), and p-value of less than 0.05 was considered to be significant.6. Ethics statementThis study was approved by Institutional Review Board of Seoul National University Bundang Hospital, and the written informed consent was received from every participant. RESULTS1. Clinical characteristics and genotypic frequency ofIL28B polymorphismThe clinical characteristics of the health check examinees and the HCV infected patients are summarized in Table 1. The rs12979860 allele frequency in the health check examinees was 88.4% for CC type, 10.9% for CT type and 0.7% for TT type. The genotypic distribution of rs8099917 was very similar to that of rs12979860 but not identical in this study. The estimated level of linkage disequilibrium from genotype frequency data showed that the two loci are tightly linked with r2 of 0.87 (data not shown).72 Gut and Liver, Vol. 8, No. 1, January 20142. Association between IL28B polymorphism and clinicaloutcome of HCV infectionThe frequency of rs12979860 CC type in the spontaneous clearance group (97.9%, n=47) was significantly higher than that (84.6%, n=260) in chronic infection group (p=0.014) (Table 1). In the chronic infection group, the CC genotype was signifi-cantly higher in chronic hepatitis group (87.9%, n=174) than in LC or HCC group (77.9%, n=86) (p=0.035). On the multivariate logistic regression analysis, rs12979860 CC type and young age less than 45 years were the independent factors for spontaneous clearance (odds ratio [OR], 8.29; 95% confidence interval [CI], 1.09 to 63.26) (Table 2) and for the better clinical outcome such as chronic hepatitis rather than LC or HCC (Table 3). It suggests the significant role of rs12979860 CC type in a favorable clini-cal outcome of HCV infection.3. Association between IL28B polymorphism and SVR ingenotype 1 HCV infectionIn a total of 260 patients of chronic infection group, 151 pa-tients (58%) were infected by genotype 1 HCV and 109 patients (42%) by genotype 2. In the 151 patients with genotype 1 infec-tion, 70 patients were treated and evaluable on the achievement of SVR. In the 70 patients with genotype 1 infection, SVR rate was 60%, and the frequency of rs12979860 CC type in SVR group (n=42) was 97.6%, while in non-SVR group (n=28) was 64.3%.On multivariate logistic regression analysis, rs12979860 CC genotype was an independent factor for SVR in the genotype 1 HCV infection (OR, 21.09; 95% CI, 2.37 to 187.82), as well as platelet count ≥140,000/µL (Table 4). Moreover, rs12979860 CC genotype was an independent factor for RVR in the genotype 1 HCV infection (OR, 22.17; 95% CI, 2.23 to 220.84), as well as HCV RNA <600,000 IU/mL on multivariate logistic regression analysis (Table 5).On the other hand, in the 109 patients with genotype 2 infec-tion, 58 patients were evaluable on SVR, which showed that SVR rate was 84.5%: the frequency of rs12979860 CC type in SVR group (n=49) was 87.8%, while in non-SVR group (n=9) was 88.9% (p=0.924). And rs12979860 CC genotype was notTable 1. The Clinical Characteristics and Genotype Frequency of Interleukin 28B (rs12979860 and rs8099917) in Health Check Examinees and Pa-tients with Hepatitis C Viral InfectionCharacteristic Health checkexaminees(n=147)Patients with HCV infection (n=307)p-value* Spontaneous recoverygroup (n=47)Chronic hepatitisgroup (n=174)LC or HCCgroup (n=86)Total(n=307)Age, yr45.0±14.246.8±16.453.6±14.565.1±10.665.1±15.2<0.001 Sex0.679 Female75 (51.0)30 (63.8)88 (50.6)45 (52.3)163 (53.1)- Male72 (49.0)17 (36.2)86 (49.4)41 (47.7)144 (46.9)-Body mass index, kg/m222.9±2.923.2±2.723.3±3.023.8±3.123.5±3.00.061 Platelet, 109/L243.4±49.9232.8±60.4199.3±53.7118.2±52.5181.5±68.2<0.001 ALT, IU/L 28.4±31.618.1±8.872.4±69.782.7±72.867.0±68.4<0.001 Albumin, g/dL 4.6±0.2 4.4±0.3 4.3±0.4 3.8±0.5 4.2±0.5<0.001γ-GT, mg/dL 31.7±28.924.8±21.164.4±89.385.1±80.764.3±82.2<0.001 Total cholesterol, mg/dL203.0±36.3188.2±37.4174.1±34.9164.1±36.8173.5±36.5<0.001 HCV RNA <6×105, IU/mL--63 (39.6)46 (56.1)115 (46.4)-HCV genotype 1--100 (57.5)51 (59.3)151 (57.6)-rs129798600.857 CC genotype130 (88.4)46 (97.9)153 (87.9)67 (77.9)266 (86.6)CT genotype16 (10.9) 1 (2.1)21 (12.1)17 (19.8)39 (12.7)TT genotype 1 (0.7)00 2 (2.3) 2 (0.7)rs8099917- TT genotype-46 (97.9)155 (89.1)70 (81.4)271 (88.3)TG genotype- 1 (2.1)19 (10.9)15 (17.4)35 (11.4)GG genotype-00 1 (1.2) 1 (0.3)Values are presented as mean±SD or number (%).HCV, hepatitis C virus; LC, liver cirrhosis; HCC, hepatocellular carcinoma; ALT, alanine aminotransferase.*p-value comparing the health check examinees (n=147) and patients with HCV infection (n=307).Kil H, et al: IL28B SNP in Korea 73related to RVR in patients with genotype 2 HCV infection (p=0.769).4. Role of IL28B SNP analysis in the current RGTA suggested algorithm using IL28B genotype and platelet count was displayed in Fig. 1 for the 70 patients with HCV genotype 1 infection who were treated and evaluable on the achievement of SVR. Among the total 70 patients, five patients (7.1%) showing IL28B non-CC type and low platelet count lower than 140,000/µL did not achieve SVR, while 48 patients (68.6%) showing IL28B CC type and platelet count higher than 140,000/µL showed SVR rate of 77%. In between, SVR rates were esti-mated from 17% to 36%. If HCV RNA level was added in the algorithm, all of 14 patients having IL28B CC type, normalTable 2. Results of Univariate and Multivariate Analyses of the Factors Associated with Spontaneous Clearance of the Hepatitis C Virus (HCV) in HCV-Infected PatientsCharacteristic Crude OR95% CI p-value Adjusted OR95% CI p-value Age, yr<45 1.00-- 1.00--≥450.300.16-0.58<0.0010.270.14-0.54<0.001 SexMale 1.00-----Female 1.690.89-3.200.112---Body mass index, kg/m2<25 1.00-----≥250.830.40-1.730.626---IL28B rs12979860Non-CC type 1.00-- 1.00--CC type8.36 1.12-62.400.0388.29 1.09-63.260.041 OR, odds ratio; CI, confidence interval; IL28B, interleukin-28B.Table 3. Results of Univariate and Multivariate Analyses of the Factors Associated with Advanced Liver Disease (Liver Cirrhosis or Hepatocellular Carcinoma) in Patients with Chronic Hepatitis C Viral InfectionCharacteristic Crude OR95% CI p-value Adjusted OR95% CI p-value Age, yr<45 1.00-- 1.00--≥4534.27 4.64-252.900.00135.63 4.79-265.09<0.001 SexMale 1.00-----Female 1.070.64-1.800.79---Body mass index, kg/m2<25 1.00-----≥250.830.46-1.510.549--HCV RNA, IU/mL<600,000 1.00-- 1.00--≥600,0000.510.30-0.880.0160.630.35-1.120.629 HCV genotype2 1.00-----1 1.080.64-1.820.778---IL28B rs12979860CC type 1.00-- 1.00--Non-CC type 2.07 1.04-4.090.038 2.23 1.04-4.760.039 OR, odds ratio; CI, confidence interval; HCV, hepatitis C virus; IL28B, interleukin-28B.74 Gut and Liver, Vol. 8, No. 1, January 2014platelet count and low HCV RNA level achieved SVR. Therefore, this algorithm could give an expected probability of SVR for each patient before antiviral therapy.Among the 70 patients with genotype 1 infection, 55 patients had complete results on the RVR, EVR and SVR. Using those 55 patients, RGT algorithm after initiation of antiviral therapy was presented in Fig. 2. RVR was achieved in 31 patients (56.4%), all of them achieved EVR, and 30 patients (97%) showed IL28B CC type. In other hand, only 4 patients (7.3%) did not achieve EVR, and did not achieve SVR, either. Therefore, those with RVR (n=31) should continue the antiviral therapy, and those without EVR (n=4) should discontinue the antiviral therapy at 12 weeks of therapy, regardless of their IL28B genotypes. It suggests that at least a total 34 patients (64%) may not need to do their IL28B SNP genotyping for the therapeutic decision once they initi-ated the antiviral therapy. Therefore, IL28B SNP genotyping was most helpful to the patients who showed EVR without RVR (n=20, 36%), because those patients having non-CC type did not achieve SVR.DISCUSSIONIn this study, in concordance with other reports,14,15 about 88% of Korean population had rs12979860 CC type of IL28B SNP, and it affected spontaneous clearance, benign clinical out-come of HCV infection, and SVR in genotype 1 HCV infection. The genotypic distribution of rs8099917 was very similar to that of rs12979860, but not identical. The algorithm using IL28B genotype and platelet count presents an expected probability of SVR in genotype 1 HCV infected patients before antiviral therapy. However, once the therapy is initiated, practical utility of IL28B genotyping seems to be limited under current strategy of RGT.The genotypic frequency of rs12979860 in the health check examinee of this study showed that CC type in 88.4%, CT type 10.9%, and TT type in 0.7%: C allele frequency of 93.9%, and T allele frequency of only 6.1%. Thomas et al.16 reported the rs12979860 C allele frequency in worldwide population, in that C allele frequency was 23% to 55% in African populations, 52% to 80% in European population, 75% to 98% in Southwest Asians, and 90% to 100% in East Asian populations including Koreans (93.5%, n=54), Chinese (93.6%, n=47), and JapaneseTable 4. Results of Univariate and Multivariate Analyses of the Factors Associated with Sustained Virologic Response in Patients with Hepatitis C Virus Genotype 1 InfectionCharacteristic Crude OR95% CI p-value Adjusted OR95% CI p-value Age, yr<45 1.00-- 1.00--≥450.310.10-0.980.0460.370.09-1.590.183 SexMale 1.00-----Female0.690.27-1.800.45---Body mass index, kg/m2<25 1.00-----≥25 1.760.61-5.090.298---Platelet, /µL<140,000 1.00-- 1.00--≥140,0007.50 2.10-26.750.002 6.62 1.68-26.070.007 ALT, IU/L<40 1.00-----40-79 1.270.36-4.480.707---≥80 1.150.36-3.680.812---HCV RNA, IU/mL<600,000 1.00-----≥600,0000.440.15-1.330.146---IL28B rs12979860Non-CC type 1.00-- 1.00--CC type23.89 2.85-200.620.00321.09 2.37-187.820.006 OR, odds ratio; CI, confidence interval; ALT, alanine aminotransferase; HCV, hepatitis C virus; IL28B, interleukin-28B.Kil H, et al: IL28B SNP in Korea 75(91.0%, n=50), which was well compatible to our results. The genotypic distribution of rs8099917 was similar to that of rs12979860, because of the strong linkage disequilibrium of the two SNPs.In this study, rs12979860 CC genotype was strongly associ-ated with spontaneous clearance of HCV infection (OR, 8.29; 95% CI, 1.09 to 63.26; p=0.041), which was compatible to the other reports.16,17 Grebely et al.18 suggested an algorithm for clinical management of acute HCV infection using IL28B geno-typing; if IL28B genotype of patients with recent HCV infection was rs8099917 GG or GT type, antiviral therapy was promptly suggested without waiting for spontaneous clearance. After acute HCV infection, about 50% to 90% of patients experi-ence chronic infection according to the presence of multiple cofactors4,19 as well as the IL28B genotype. In addition, more advanced complication of HCV infection such as LC or HCC was also significantly related to non-CC type of IL28B in this study. The multiple logistic regression analysis confirmed that IL28B non-CC type was independently associated with LC or HCC (OR, 2.23; 95% CI, 1.04 to 4.76; p=0.039). Fabris et al.20 showed that rs12979860 T allele was more prevalent in patients with HCV-related cirrhosis than in other etiologies of cirrhosis, and carriage of this allele seemed to augment the risk of developing HCC in Italian patients with HCV-related cirrhosis who un-derwent liver transplantation. These results suggest that IL28B genotype shows a strong effect on the clinical outcomes of HCV infection. However, because of the small sample size in this study, further study to confirm the result is warranted.In concordance with previous GWAS results,8-11 this study also confirmed that rs12979860 CC genotype was strongly as-sociated with SVR in Korean patients with HCV genotype 1 infection (OR, 21.09; 95% CI, 2.37 to 182.82; p=0.006), as well as platelet count, which was an indirect marker of advanced fibrosis. This result suggests that high frequency of IL28B CC type in Asians including Koreans can be an explanation for a higher SVR reported in Asians than in Caucasians or AfricanTable 5. Results of Univariate and Multivariate Analyses of the Factors Associated with Rapid Virologic Response in Patients with Hepatitis C Vi-rus Genotype 1 InfectionCharacteristic Crude OR95% CI p-value Adjusted OR95% CI p-value Age, yr<45 1.00-----≥450.440.15-1.230.133---SexMale 1.00-----Female 2.250.82-6.210.117---Body mass index, kg/m2<25 1.00-----≥250.820.29-2.320.706---Platelet, /µL<140,000 1.00-----≥140,0000.720.18-2.830.636---ALT, IU/L<40 1.00-----40-79 1.220.34-4.380.758---≥80 1.170.35-3.880.802---HCV RNA, IU/mL<600,000 1.00-- 1.00--≥600,0000.360.12-1.100.0730.220.06-0.880.033IL28B rs12979860Non-CC type 1.00-- 1.00--CC type14.14 1.67-119.870.01522.17 2.23-220.840.008 OR, odds ratio; CI, confidence interval; ALT, alanine aminotransferase; HCV, hepatitis C virus; IL28B, interleukin-28B.76 Gut and Liver, Vol. 8, No. 1, January 2014Fig. 1. A suggested algorithm for theexpected probability of sustained vi-rologic response (SVR) according tothe presence of the interleukin-28B(IL28B) polymorphism (rs12979860),platelet count, and hepatitis C virus(HCV) RNA levels in Korean pa-tients infected with HCV genotype1. Among the 70 total patientsincluded in this algorithm, all fivepatients exhibiting the IL28B non-CC type and a low platelet count (7%)did not achieve SVR. However, all14 patients exhibiting the IL28B CCtype, a normal platelet count, andlow HCV RNA levels (20%) achievedSVR. Between these extremes, SVRrates ranged from 17% to 68%.Fig. 2. Practical value of the interleukin-28B (IL28B) polymorphism (rs12979860) under the current strategy of response-guided therapy in Korean patients infected with hepatitis C virus (HCV) genotype 1. According to the current response-guided treatment algorithm, all of the patients with rapid virologic response (RVR) (31 of 55, 56%) should continue the defined duration of therapy, and all of the patients without early virologic response (EVR) (4 of 55, 7%) should discontinue the antiviral therapy regardless of the result of the IL28B genotyping, which suggests that there is no need to determine the IL28B SNP genotype in 63% of the patients. IL28B single nucleotide polymorphism (SNP) genotyping may be helpful only in those patients achieving EVR without RVR (36%) because patients with the non-CC type did not achieve sustained virologic response (SVR).Kil H, et al: IL28B SNP in Korea 77Americans. However, the IL28B genotype was not associated with SVR in genotype 2 infection in this study, which was con-troversial.11,14,21-23The molecular mechanism for IL28B in the pathogenesis of HCV infection was not elucidated. Nevertheless, IL28B seems to play an important role in immune response. The inhibition of HCV replication in vitro by interferon-λ showed the similar ef-ficiency to type 1 interferon, and clinical trials using pegylated interferon-λ in human patients showed similar antiviral ef-fect to pegylated interferon-a.24,25 Recent experimental study showed anti-tumor activity for interferon-λ in various cancer cell lines.26,27As reported in the previous study,28 we presented a pretreat-ment prediction algorithm for SVR using IL28B genotype and platelet count in 70 patients with genotype 1 HCV infection, which provides a good prediction model for SVR before antivi-ral therapy. The IL28B SNP is the most useful predictor before antiviral therapy, and the RVR is that during antiviral therapy. To avoid some adverse events developed during the first 4 weeks of antiviral therapy, IL28B genotyping should be per-formed. If then, should we perform IL28B genotyping for all the patients who are going to receive antiviral therapy in the real practice setting? According to the suggested algorithm, once the therapy is initiated, practical utility of IL28B genotyping seems to be limited under current strategy of RGT, because about 63% of the treated patients including the patients with RVR and the patients without EVR may not need to do their IL28B SNP genotyping for the therapeutic decision. As long as we follow RGT for East Asian patients, routine testing of the IL28B SNP in HCV genotype 1 infection should be considered in the con-text of adequate cost-effectiveness, because almost all of them have IL28B CC genotype, and RGT itself determines about two-thirds of the response. In the meanwhile, IL28B SNP genotyping might be helpful for the patients who showed EVR but no RVR. However, this result should be validated in the further study, because of small number of included patients. There are several limitations of this study such as the retrospective design and incomplete data on the RVR or EVR, especially lack of data on complete EVR, the small sample size and the cross-sectional na-ture of the study.In conclusion, about 90% of Koreans had the rs12979860 CC genotype of IL28B SNP, and the IL28B SNP was an independent predictor of spontaneous clearance, favorable clinical outcomes of HCV infection, and SVR in genotype 1 HCV infection. It may be helpful in the clinical settings if the findings were carefully applied to selected patients in Korea.CONFLICTS OF INTERESTNo potential conflict of interest relevant to this article was reported.ACKNOWLEDGEMENTSThis study was supported by research grant from the Korea National Institute of Health, Grant no. 2011-E4-200300. REFERENCES1. Lavanchy D. The global burden of hepatitis C. Liver Int2009;29(Suppl 1):74-81.2. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. Thecontributions of hepatitis B virus and hepatitis C virus infec-tions to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529-538.3. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med2001;345:41-52.4. European Association for the Study of the Liver. EASL ClinicalPractice Guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245-264.5. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB; Ameri-can Association for Study of Liver Diseases. An update on treat-ment of genotype 1 chronic hepatitis C virus infection: 2011 prac-tice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011;54:1433-1444.6. Kim JY, Won JE, Jeong SH, et al. Acute hepatitis C in Korea: dif-ferent modes of infection, high rate of spontaneous recovery, and low rate of seroconversion. J Med Virol 2011;83:1195-1202.7. Yu ML, Chuang WL. Treatment of chronic hepatitis C in Asia:when East meets West. J Gastroenterol Hepatol 2009;24:336-345.8. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28Bpredicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401.9. Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide associa-tion of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105-1109.10. Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associatedwith response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009;41:1100-1104.11. Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28Bis associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010;138:1338-1345.12. Jensen DM, Pol S. IL28B genetic polymorphism testing in the eraof direct acting antivirals therapy for chronic hepatitis C: ten years too late? Liver Int 2012;32(Suppl 1):74-78.13. Bruix J, Sherman M; American Association for the Study of LiverDiseases. Management of hepatocellular carcinoma: an update.Hepatology 2011;53:1020-1022.14. Sinn DH, Kim YJ, Lee ST, et al. Association of a single nucleo-tide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients. J Gastroenterol Hepatol 2011;26:1374-1379.。
肠-肝轴在炎症性肠病发病机制中的作用
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炎症性肠病（ｉｎｆｌａｍｍａｔｏｒｙｂｏｗｅｌｄｉｓｅａｓｅ，ＩＢＤ）包括溃疡 性结 肠 炎 （ｕｌｃｅｒａｔｉｖｅｃｏｌｉｔｉｓ，ＵＣ）和 克 罗 恩 病 （Ｃｒｏｈｎ’ｓ ｄｉｓｅａｓｅ，ＣＤ），是一种病因和发病机制未明的慢性复发性肠 道炎性疾病，肝胆系统症状是其最常见的肠外表现。近期报 告指出，１．４％ ～７．５％的 ＩＢＤ患者伴发原发性硬化性胆管炎 （ｐｒｉｍａｒｙｓｃｌｅｒｏｓｉｎｇｃｈｏｌａｎｇｉｔｉｓ，ＰＳＣ），而 ７０％ ～８０％ 的 ＰＳＣ 患者在病程中出现 ＩＢＤ，提示 ＩＢＤ与肝肠病变可能存在相互 关联的发 病 机 制［１］。肠 道 与 肝 脏 在 结 构 和 功 能 上 紧 密 联 系、相互影响，称之为“肠肝轴”。近年研究发现，胆汁酸肠 肝循环异常、肠道细菌和内毒素移位以及淋巴细胞归巢紊乱 可能通过肠肝轴参与 ＩＢＤ的发病。本文就肠肝轴在 ＩＢＤ 发病机制中的作用作一综述。
二、胆汁酸与 ＩＢＤ １．胆汁酸的肠肝循环：胆汁酸是胆固醇代谢的终产物， 是机体肠肝轴的重要成分。机体的胆汁酸库共约 ３～５ｇ， 远远无法满足机体的需求，故借助有效的肠肝循环机制使有 限的胆汁酸能反复利用。约 ９５％排入肠道的胆汁酸可在肠 道被重吸收，其余 ５％则是每天随粪便排出的最少损失量。 结合型胆汁酸在回肠末端通过主动转运被有效地重吸收，少 量未结合型胆汁酸在小肠和结直肠中通过被动扩散被重吸 收。肝细胞则通过与门静脉血流直接接触的基底侧膜摄取
【疾病名】戈谢病【英文名】Gaucherdisease【缩写】【别名】家族性脾性...
【疾病名】戈谢病【英文名】Gaucher disease【缩写】【别名】家族性脾性贫血；葡萄糖脑苷脂病；葡萄糖脑苷脂酶缺乏症；cerebroside lipoidosis；cerebrosidosis；familial splenic anemia；Gaucher病；glucosylceramide lipoidosis；戈谢脾肿大；脑甙病；脑甙沉积病；脑苷脂沉积病；脑苷脂沉积症；脑苷脂网状内皮细胞病；葡萄糖脑酰胺沉积病；神经病变性急性戈谢综合征【ICD号】E75【概述】戈谢病(Gauchers disease)又称脑苷脂沉积病(cerebrosidosis或cerebroside lipoidosis)、戈谢脾肿大、神经病变性急性戈谢综合征、脑苷脂网状内皮细胞病、家族性脾性贫血(familial splenic anemia)、葡萄糖脑酰胺沉积病(glucosylceramide lipoidosis)等，是一种家族性糖脂代谢性疾病。
该症于1882年首先由Gaucher报告，其临床特点是肝脾肿大、骨痛，Ⅱ、Ⅲ型患儿有中枢神经系统受累的表现。
戈谢细胞是本症的特征。
【流行病学】本病临床较为少见，尚未查到相关的发病率统计学资料。
本病不同类型起病年龄不同。
【病因】脑苷脂沉积病为常染色体隐性遗传病，基因定位于1q21，是由于β-葡萄糖苷酶(β-glucosidase)先天性缺乏，致使葡萄糖脑苷脂(glucocerebroside)不能水解而在网状内皮系统大量沉积，从而引起相应的临床表现。
【发病机制】本病为常染色体隐性遗传，多发生于年长儿，可一家子女数人患病，为网状内皮细胞增多症中主要累及脾脏的一种疾病。
目前证实由于β-葡萄糖苷脂酶遗传性缺乏所致，使葡萄糖脑苷脂蓄积在肝、脾、骨骼和中枢神经系统的单核巨噬细胞内，而造成肝脾肿大，骨骼受累和神经系统症状。
葡萄糖脑苷脂是一种糖脂，溶于水，是由长链的氨基乙醇神经鞘氨醇和长链的脂肪酸在C的部位相连，此种化合物称为N-酰基鞘氨醇，1个分子的葡萄糖由β-糖苷链接于鞘氨醇的C部位而合成。
用器官表达情感的英语单词
用器官表达情感的英语单词When it comes to expressing emotions in English, there's arich vocabulary that often uses references to body parts, particularly internal organs. Here are some common English words and phrases that use organ-related terms to convey feelings:1. Heart: Often symbolizes love or emotional strength.- Falling in love: Becoming romantically interested in someone.- Heartbroken: Experiencing deep emotional pain, usually after a relationship ends.- Wear your heart on your sleeve: To openly show your emotions.2. Gut: Refers to one's intuition or inner feelings.- Gut feeling: An intuitive sense of what is true or right. - Follow your gut: To trust your instincts.3. Liver: While not directly used to express emotions, it's part of the phrase "to have a good/bad liver," which in some cultures refers to being a heavy/light drinker.4. Kidneys: Rarely used in emotional contexts, but "selling a kidney" might be used humorously to express desperation.5. Lungs: Can be used metaphorically to express the intensity of an emotion, especially in the context of breath.- Take a deep breath: Often said to calm down or preparefor a difficult situation.6. Brain: Associated with thinking and mental states.- On the brain: Preoccupied with a particular thought.- Pick someone's brain: To seek advice or knowledge from someone.7. Stomach: Can indicate feelings of nervousness or excitement.- Butterflies in the stomach: Feeling nervous or excited about something.- Stomach is in knots: Feeling very anxious or upset.8. Gallbladder: Not typically used in emotional expressions, but "gall" can refer to anger or resentment.- With a lot of gall: With a lot of nerve or audacity.9. Spleen: Not commonly used in emotional contexts in English.10. Intestines: Sometimes used humorously to expressdiscomfort or unease.- Turn one's stomach: To make someone feel sick or disgusted.11. Eyes: Often the windows to the soul, used to express a range of emotions.- Crying one's eyes out: Crying a lot.- Rolling one's eyes: To express disbelief or annoyance.12. Ears: Can be used to express the reception of informationor the desire for attention.- Burning ears: When you think someone is talking about you.- Lend an ear: To listen to someone.These expressions are part of the colorful and figurative language used in English to convey a wide range of emotional states. Understanding these can help non-native speakers to better communicate their feelings and to interpret the emotional nuances in conversations.。
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Gut Liver. 2016 Nov 15;10(6):932-938. doi: 10.5009/gnl15588.
Irritable Bowel Syndrome, Particularly the Constipation-Predominant Form, Involves an Increase in Methanobrevibacter smithii, Which Is Associated with Higher Methane Production.
Ghoshal U1, Shukla R1, Srivastava D2, Ghoshal UC2.
Author information
1
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India.
2
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India.
Abstract
BACKGROUND/AIMS:
Because Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC).
METHODS:
Quantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers.
RESULTS:
Of 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not
sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log₁₀5.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBS-C compared to IBS-D patients (Log₁₀6.1 [5.5 to 6.6] vs 3.4 [0.6 to 5.7], p=0.001); the copy number negatively correlated with the stool frequency (R=-0.420, p=0.003). The M. smithii copy number was higher among methane-producers than nonproducers (Log₁₀6.4, IQR [5.7 to 7.4] vs 4.1 [1.8 to 5.8], p=0.001). Using a receiver operating characteristic curve, the best cutoff for M. smithii among methane producers was Log₁₀6.0 (sensitivity, 64%; specificity, 86%; area under curve [AUC], 0.896). The AUC for breath methane correlated with the M. smithii copy number among methane producers (r=0.74, p=0.008). Abdominal bloating was more common among methane producers (n=9/11 [82%] vs 5/14 [36%], p=0.021).
CONCLUSIONS:
Patients with IBS, particularly IBS-C, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads.。