PP1_172889-26-8_DataSheet_MedChemExpress
Genotoxicity A Standard Battery for Genotoxicity Testing
The European Agency for the Evaluation of Medicinal ProductsHuman Medicines Evaluation UnitICH - Technical Coordination - R. Bass 7 Westferry Circus, Canary Wharf, London E14 4HB, UK ICH Topic S 2 BGenotoxicity: A Standard Battery forGenotoxicity Testing of PharmaceuticalsStep 4, Consensus guideline, 16 July 1997NOTE FOR GUIDANCE ON GENOTOXICITY:A STANDARD BATTERY FOR GENOTOXICITY TESTINGOF PHARMACEUTICALS(CPMP/ICH/174/95)TRANSMISSION TO CPMPOctober 1996TRANSMISSION TO INTERESTED PARTIESOctober 1996COMMENTS REQUESTED BEFOREApril 1997FINAL APPROVAL BY CPMPSeptember 1997DATE FOR COMING INTO OPERATION March 1998GENOTOXICITY: A STANDARD BATTERY FORGENOTOXICITY TESTING OF PHARMACEUTICALS[ICH Harmonised Tripartite Guideline]TABLE OF CONTENTS1.INTRODUCTION (2)2.GENERAL PURPOSE OF GENOTOXICITY TESTING (2)3.THE STANDARD TEST BATTERY FOR GENOTOXICITY (2)4.MODIFICATIONS OF THE 3-TEST BATTERY (4)4.1Limitations to the use of bacterial test organisms (4)4.2Compounds bearing structural alerts for genotoxic activity (4)4.3Limitations to the use of standard in vivo tests (4)4.4Additional genotoxicity testing in relation to the carcinogenicity bioassay (5)4.4.1 Evidence for tumour response (5)4.4.2 Structurally unique chemical classes (5)5.STANDARD PROCEDURES FOR IN VITRO TESTS (5)6.NOTES (6)7.GLOSSARY (8)1.INTRODUCTIONTwo fundamental areas in which harmonisation of genotoxicity testing for pharmaceuticals is considered necessary are the scope of this guideline: i) Identification of a standard set of tests to be conducted for registration. ii) The extent of confirmatory experimentation in in vitro genotoxicity tests in the standard battery. Further issues that were considered necessary for harmonisation can be found in the ICH guideline "Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals" (ICH topic S2A). The two ICH guidelines on genotoxicity complement each other and therefore should be used together as ICH guidance principles for testing of a pharmaceutical for potential genotoxicity.2.GENERAL PURPOSE OF GENOTOXICITY TESTINGGenotoxicity tests can be defined as in vitro and in vivo tests designed to detect compounds which induce genetic damage directly or indirectly by various mechanisms. These tests should enable a hazard identification with respect to damage to DNA and its fixation. Fixation of damage to DNA in the form of gene mutations, larger scale chromosomal damage, recombination and numerical chromosome changes is generally considered to be essential for heritable effects and in the multi-step process of malignancy, a complex process in which genetic changes may play only a part. Compounds which are positive in tests that detect such kinds of damage have the potential to be human carcinogens and/or mutagens, i.e. may induce cancer and/or heritable defects. Because the relationship between exposure to particular chemicals and carcinogenesis is established for man, whilst a similar relationship has been difficult to prove for heritable diseases, genotoxicity tests have been used mainly for the prediction of carcinogenicity. Nevertheless, because germ line mutations are clearly associated with human disease, the suspicion that a compound may induce heritable effects is considered to be just as serious as the suspicion that a compound may induce cancer. In addition, the outcome of such tests may be valuable for the interpretation of carcinogenicity studies.3.THE STANDARD TEST BATTERY FOR GENOTOXICITYRegistration of pharmaceuticals requires a comprehensive assessment of their genotoxic potential. It is clear that no single test is capable of detecting all relevant genotoxic agents. Therefore, the usual approach should be to carry out a battery of in vitro and in vivo tests for genotoxicity. Such tests are complementary rather than representing different levels of hierarchy.The general features of a standard test battery can be outlined as follows:i)It is appropriate to assess genotoxicity in a bacterial reverse mutation test. This test hasbeen shown to detect relevant genetic changes and the majority of genotoxic rodent carcinogens.ii)DNA damage considered to be relevant for mammalian cells and not adequately measured in bacteria should be evaluated in mammalian cells. Several mammalian cell systems are in use: systems that detect gross chromosomal damage (in vitro tests forstructural and numerical chromosomal aberrations), systems that detect primarily gene mutations (see Note 1), and a system that detects gene mutations and clastogenic effects (mouse lymphoma tk assay) (see Note 2). The information given in Notes 3 and4 demonstrate that with appropriate test protocols (see Section 5) the various in vitrotests for chromosomal damage and the mouse lymphoma tk assay yield results with a high level of congruence for compounds that are regarded as genotoxic but yield negative results in the bacterial reverse mutation assay. Therefore, these systems are currently considered interchangeable when used together with other genotoxicity tests in a standard battery for genotoxicity testing of pharmaceuticals, if these test protocols are used.iii)An in vivo test for genetic damage should usually be a part of the test battery to provide a test model in which additional relevant factors (absorption, distribution metabolism, excretion) that may influence the genotoxic activity of a compound are included. As a result, in vivo tests permit the detection of some additional genotoxic agents (see Note 5). An in vivo test for chromosomal damage in rodent hematopoietic cells fulfills this need. This in vivo test for chromosomal damage in rodents could be either an analysis of chromosomal aberrations in bone marrow cells or an analysis of micronuclei in bone marrow or peripheral blood erythrocytes.The following standard test battery is recommended based upon the considerations mentioned above:i) A test for gene mutation in bacteria.ii)An in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay.iii)An in vivo test for chromosomal damage using rodent hematopoietic cells.For compounds giving negative results, the completion of this 3-test battery, performed and evaluated in accordance with current recommendations, will usually provide a sufficient level of safety to demonstrate the absence of genotoxic activity (see Note 6). Compounds giving positive results in the standard test battery may, depending on their therapeutic use, need to be tested more extensively (see ICH Guideline “Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals”).The suggested standard set of tests does not imply that other genotoxicity tests are generally considered as inadequate or inappropriate (e.g. tests for measurement of DNA adducts, DNA strand breaks, DNA repair or recombination). Such tests serve as options in addition to the standard battery for further investigation of genotoxicity test results obtained in the standard battery. Furthermore, molecular techniques to study mechanisms of genotoxicity in the standard battery systems may be useful for risk assessment. Only under extreme conditions in which one or more tests comprising the standard battery cannot be employed for technical reasons, alternative validated tests can serve as substitutes. For this to occur, sufficient scientific justification should be provided to support the argument that a given standard battery test is not appropriate.The standard battery does not include an independent test designed specifically to test for aneuploidy. However, information on this type of damage may be derived from the tests for chromosomal damage in vitro and in vivo. Elements of the standard protocols that provide such information are elevations in the mitotic index, polyploidy induction and micronucleus evaluation. There is also limited experimental evidence that aneuploidy inducers can be detected in the mouse lymphoma tk assay (see Note 4). In such cases, further testing may be needed.4.MODIFICATIONS OF THE 3-TEST BATTERYThe following sections give situations where the standard 3-test battery may need modification.4.1Limitations to the use of bacterial test organismsThere are circumstances where the performance of the bacterial reverse mutation test does not provide appropriate or sufficient information for the assessment of genotoxicity. This may be the case for compounds that are excessively toxic to bacteria (e.g. some antibiotics) and compounds thought or known to interfere with the mammalian cell replication system (e.g. topoisomerase inhibitors, nucleoside analogues, or inhibitors of DNA metabolism). For these cases, usually two in vitro mammalian cell tests should be performed using two different cell types and of two different endpoints [gene mutation (see Note 1) and chromosomal damage]. Nevertheless, it is still important to perform the bacterial reverse mutation test (see Note 7); either a full test or a limited (range-finding) test (see Section 5) may be appropriate.4.2Compounds bearing structural alerts for genotoxic activityStructurally alerting compounds (see Note 8) are usually detectable in the standard 3-test battery. However, compounds bearing structural alerts that have given negative results in the standard 3-test battery may necessitate limited additional testing. The choice of additional test(s) or protocol modification(s) depend on the chemical nature, the known reactivity and metabolism data on the structurally alerting compound under question (see Note 9 and ICH “Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals”).4.3Limitations to the use of standard in vivo testsThere are compounds for which standard in vivo tests do not provide additional useful information. This includes compounds for which data from studies on toxicokinetics or pharmacokinetics indicate that they are not systemically absorbed and therefore are not available for the target tissues in standard in vivo genotoxicity tests. Examples of such compounds are some radioimaging agents, aluminum based antacids, and some dermally applied pharmaceuticals. In cases where a modification of the route of administration does not provide sufficient target tissue exposure, it may be appropriate to base the evaluation only on in vitro testing.4.4Additional genotoxicity testing in relation to the carcinogenicity bioassay4.4.1Evidence for tumour responseAdditional genotoxicity testing in appropriate models may be conducted for compounds that were negative in the standard 3-test battery but which have shown effects in carcinogenicity bioassay(s) with no clear evidence for a non-genotoxic mechanism. To help understand the mechanism of action, additional testing can include modified conditions for metabolic activation in in vitro tests or can include in vivo tests measuring genetic damage in target organs of tumour induction (e.g. liver UDS test, 32P-postlabelling, mutation induction in transgenes, molecular characterisation of genetic changes in tumour-related genes).4.4.2Structurally unique chemical classesOn rare occasions, a completely novel compound in a unique structural chemical class will be introduced as a pharmaceutical. When such a compound will not be tested in chronic rodent carcinogenicity bioassays, further genotoxicity evaluation may be invoked.5.STANDARD PROCEDURES FOR IN VITRO TESTSReproducibility of experimental results is an essential component of research involving novel methods or unexpected findings; however, the routine testing of chemicals with standard, widely used genotoxicity tests need not always be completely replicated. These tests are sufficiently well characterised and have sufficient internal controls that repetition can usually be avoided if protocols with built-in confirmatory elements, such as those outlined below, are used.For both bacterial and mammalian cell gene mutation tests, the results of a range-finding test can be used to guide the selection of concentrations to be used in the definitive mutagenicity test. By these means, a range-finding test may supply sufficient data to provide reassurance that the reported result is the correct one. In bacterial mutagenicity tests, preliminary range-finding tests performed on all bacterial strains, with and without metabolic activation, with appropriate positive and negative controls, and with quantification of mutants, may be considered a sufficient replication of a subsequent complete test. Similarly, a range-finding test may also be a satisfactory substitute for a complete repeat of a test in gene mutation tests with mammalian cells other than the mouse lymphoma tk assay (see below) if the range-finding test is performed with and without metabolic activation, with appropriate positive and negative controls, and with quantification of mutants (see Note 10).For the cytogenetic evaluation of chromosomal damage in vitro, the test protocol includes the conduct of tests with and without metabolic activation, with appropriate positive and negative controls, where the exposure to the test articles is 3 to 6 hours and a sampling time of approximately 1.5 normal cell cycles from the beginning of the treatment. A continuous treatment without metabolic activation up to the sampling time of approximately 1.5 normal cell cycles is needed in case of a negative result for the short treatment period without metabolic activation. Certain chemicals may be more readily detected by longer treatment or delayed sampling times, e.g. some nucleoside analogues or some nitrosamines. Negative results in the presence of a metabolic activation system may need confirmation on a case by case basis (see Note 11). In any case information on the ploidy status should be obtained byrecording the incidence of polyploid cells as a percentage of the number of metaphase cells. An elevated mitotic index or an increased incidence of polyploid cells may give an indication of the potential of a compound to induce aneuploidy. In such cases, further testing may be needed.For the mouse lymphoma tk assay, the test protocol includes the conduct of tests with and without metabolic activation, with appropriate positive and negative controls, where the exposure to the test articles is 3 to 4 hours. A continuous treatment without metabolic activation for approximately 24 hours is needed in case of a negative result for the short treatment without metabolic activation (see Note 4). Negative results in the presence of a metabolic activation system may need confirmation on a case by case basis (see Note 11). In any case, an acceptable mouse lymphoma tk assay includes (i) the incorporation of positive controls which induces mainly small colonies, (ii) colony sizing for positive controls, solvent controls and at least one positive test compound dose (should any exist), including the culture that gave the greatest mutant frequency.Following such testing, further confirmatory testing in the case of clearly negative or positive test results is not usually needed.Ideally it should be possible to declare test results as clearly negative or clearly positive. However, test results sometimes do not fit the predetermined criteria for a positive or negative call and therefore are declared “equivocal”. The application of statistical methods aids in data interpretation, however, adequate biological interpretation is of critical importance. Nonetheless, further testing is usually indicated for equivocal results.6.NOTES1)Test approaches currently accepted for the assessment of mammalian cell genemutation involve the tk locus using mouse lymphoma L5178Y cells or human lymphoblastoid TK6 cells, the hprt locus using CHO cells, V79 cells, or L5178Y cells, or the gpt locus using AS52 cells.2)The molecular dissection of mutants induced at the tk locus shows a broad range ofgenetic events including point mutations, deletions, translocations, recombinations etc.Small colony mutants have been shown to predominantly lack the tk b allele as a consequence of structural or numerical alterations or recombinational events. There is some evidence that other loci, such as hprt or gpt are also sensitive to large deletion events. However, due to the X-chromosomal origin of the hprt gene which is probably flanked by essential genes, large scale deletionevents or numerical alterations often do not give rise to mutant colonies, thus limiting the sensitivity of this genetic locus relative to the tk locus for the detection of a wide range of genetic changes.3)With respect to the cytogenetic evaluation of chromosomal damage, it is notuncommon for the systems currently in use, i.e. several systems with permanent mammalian cells in culture and human lymphocytes either isolated or in whole blood, to give different results for the same test compound. However, there is evidence that some of the differences observed have been due to protocol differences. This may be minimised by using the procedures described in Section 5.For the great majority of presumptive genotoxic compounds that were negative in a bacterial reverse mutation assay, the data on chromosomal damage in vitro and mouse lymphoma tk results are in agreement. Several reliable studies indicate that the mouse lymphoma tk assay is able to detect compounds that induce structural and numerical chromosomal damage. For safety testing of pharmaceuticals, the mouse lymphoma tk assay is considered an acceptable alternative to the direct analysis of chromosomal damage in vitro. Although colony sizing is an essential element of the mouse lymphoma tk assay test protocol, it gives only limited information on the type of damage induced in mutant colonies. Further mechanistic investigations may be used to assess the nature of cytogenetic changes induced by clastogens and aneuploidy inducers in the mouse lymphoma tk assay. Such information could be provided by studies to demonstrate the loss of the tk gene or the loss of the chromosome carrying the tk gene.4)The detection of a number of different nucleoside analogues and base analogues isenhanced for the mouse lymphoma tk assay when the treatment protocol for both agar and microtitre methods include a 24 hour treatment regimen in the absence of an exogenous metabolic activation system. Similarly, the detection of aneuploidy inducers is enhanced if a 24 hour treatment regimen is used with the microtitre method. Currently, there is no evidence to support this conclusion for the soft agar method. The specificity of the test protocol, i.e. to obtain correct test results for presumptive non-genotoxic compounds, does not change significantly using a 24 hour treatment in the microtitre method. For the soft agar method there appears to be a reduction in specificity under the same treatment regimen. Based on this information, the microtitre method is recommended for use in the standard battery.5)There are a small but significant number of genotoxic carcinogens that are reliablydetected by the bone marrow tests for chromosomal damage that have yielded negative/weak/conflicting results in the pairs of in vitro tests outlined in the standard battery options e.g. bacterial reverse mutation plus one of a selection of possible tests with cytogenetic evaluation of chromosomal damage or bacterial mutation plus the mouse lymphoma tk assay. Carcinogens such as procarbazine, hydroquinone, urethane and benzene fall into this category.6)The continuing evolution of short-term tests and test methodologies will afford new,more sensitive, more practical, more expeditious, and more economical techniques for detection of genotoxic compounds. Some of these may ultimately replace the genotoxicity tests used for regulatory purposes. Among the more promising tests, the in vitro micronucleus test appears to offer potential for screening purposes.7)Some antibacterial agents, albeit highly toxic to the tester strains, are detected asgenotoxic at very low, sub-lethal concentrations in the bacterial reverse mutation test(e.g. nitrofuran antibiotics).8)Certain structurally alerting molecular entities are recognised as being causally relatedto the carcinogenic and/or mutagenic potential of chemicals. Examples of structural alerts include alkylating electrophilic centers, unstable epoxides, aromatic amines, azo-structures, N-nitroso-groups, aromatic nitro-groups.9)For some classes of compounds with specific structural alerts, it is established thatspecific protocol modifications/additional tests are necessary for optimum detection of genotoxicity (e.g. molecules containing an azo-group, glycosides, compounds such as nitroimidazoles requiring nitroreduction for activation, compounds such as phenacetin requiring another rodent S9 for metabolic activation). The additional testing needed when the chosen 3-test battery yields negative results for a structurally alerting test compound could consist of such modifications.10)The dose range-finding study should (i) give information on the shape of the toxicitydose-response curve if the test compound exhibits toxicity, (ii) include highly toxic concentrations, (iii) include quantification of mutants in the cytotoxic range. If a compound were not toxic, then mutants should nevertheless be quantified.11) A repetition of a test using the identical source and concentration of the metabolicactivation system is usually not necessary. A modification of the metabolic activation system may be indicated for certain chemical classes where knowledge is available on specific requirements of metabolism. This would usually invoke the use of an external metabolising system which is known to be competent for the metabolism/activation of the class of compound under test.7.GLOSSARYCytogenetic evaluation: chromosome structure analysis in mitosis or meiosis by light microscopyDNA adduct: (covalent) binding of chemicals to DNADNA repair: reconstitution of damaged DNA sequenceDNA strand breaks: single or double strand scissions in the DNANumerical chromosome changes: chromosome numbers different from the original haploid or diploid set of chromosomes; for cell lines, chromosome numbers different from the modal chromosome setRecombination: breakage and balanced or unbalanced rejoining of DNATransgene: an exogenous or foreign gene inserted into the host genome, either into somatic cells or germ lline cells。
恩格列净联合利格列汀治疗2型糖尿病的临床疗效研讨
·药物与临床·糖尿病新世界 2023年11月恩格列净联合利格列汀治疗2型糖尿病的临床疗效研讨郑伟坤，陈文娜，薛笑楠，陈琳，官雯娟鹰潭市人民医院内分泌科，江西鹰潭335000[摘要]目的探讨对2型糖尿病患者采用恩格列净+利格列汀药物展开疾病治疗后获得临床效果。
方法选取2022年9月—2023年9月鹰潭市人民医院收治的60例2型糖尿病患者为研究对象，依据为投掷硬币法分为参照组和研究组，各30例。
参照组采用利格列汀治疗；研究组在参照组基础上加用恩格列净治疗。
对比两组2型糖尿病患者的药物治疗总有效率、炎症因子水平、血糖以及胰岛素指标水平、生存质量评分以及不良反应发生率。
结果研究组药物治疗总有效率、炎症因子水平、血糖以及胰岛素指标水平、生存质量评分优于参照组，差异有统计学意义（P<0.05）；两组不良反应（恶心呕吐、头晕头痛、腹痛腹泻、过敏）总发生率比较，差异无统计学意义（P>0.05）。
结论临床对2型糖尿病患者采用恩格列净+利格列汀药物治疗，提高患者用药疗效，改善炎症因子水平，降低血糖以及胰岛素指标水平，提高生存质量，可以获得显著效果。
[关键词] 恩格列净；利格列汀；2型糖尿病；炎症因子；血糖；胰岛素水平；生存质量；不良反应[中图分类号] R59 [文献标识码] A [文章编号] 1672-4062（2023）11（b）-0121-04Study on the Clinical Efficacy of Empagliflozin Combined with Linagliptin in the Treatment of Type 2 Diabetes MellitusZHENG Weikun, CHEN Wenna, XUE Xiaonan, CHEN Lin, GUAN WenjuanDepartment of Endocrinology, Yingtan People's Hospital, Yingtan, Jiangxi Province, 335000 China[Abstract] Objective To explore the clinical effect of empagliflozin + linagliptin in type 2 diabetes mellitus.Methods 60 cases of type 2 diabetes mellitus patients in Yingtan People's Hospital from September 2022 to Septem⁃ber 2023 were selected, they were divided into reference group and study group according to the coin toss method, with 30 cases in each group. The reference group was treated with linagliptin, the study group added emaglipzin to the reference group. The total effective rate, inflammatory factor level, blood glucose and insulin index level, quality of life score and incidence of adverse reactions were compared between the two groups of patients with type 2 diabetes.Results The total response rate, inflammatory factor level, blood glucose, insulin index level and quality of survival score in the study group were better than the reference group, and the differences were statistically significant (P< 0.05); and the total incidence of adverse effects (nausea, vomiting, dizziness, headache, abdominal pain, diarrhea, al⁃lergy) of the two groups, the difference was not statistically significant (P>0.05). Conclusion Clinical treatment with empagliflozin + linagliptin in patients with type 2 diabetes can improve the efficacy of medication, improve the level of inflammatory factors, reduce blood glucose and insulin indicators, and improve the quality of life, which can achieve significant effects.[Key words] Empagliflozin; Linagliptin; Type 2 diabetes mellitus; Inflammatory factor; Blood glucose; Insulin level; Survival quality; Adverse reaction2型糖尿病属于全身代谢性疾病一种，其以胰岛素抵抗作为主要表现。
PP1Src抑制剂-碧云天
方法
次。Lck的来源是LSTRA细胞，或使用牛痘表达系统表达Lck的HeLa细胞。FynT通过牛痘表达系统在 HeLa细胞中表达。细胞(12.5×106ml)在裂解缓冲液(20mM Tris，pH 8.0，150mM NaCl，0.5% Nonidet P-
40和23胰蛋白酶抑制单位/ml抑肽酶)中裂解，裂解物在Eppendorf管中通过14000cpm转速下在4ºC环境中
体内研究 N/A
临床实验 N/A
特征
N/A
相关实验数据(此数据来自于公开文献，碧云天并不保证其有效性)：
酶活性检测实验
使用1X PBS按1:20稀释 酸处理过的烯醇化酶，然后按100ml再分装到Nunc96孔高蛋白结合实验板中。
然后吸除实验孔，使用0.5%牛血清，1X PBS在37ºC下抑制1小时，然后每孔使用300ml 1X PBS洗涤5
生物信息：
产品描述 PP1是一种有效的Src选择性抑制剂，作用于Lck/Fyn时，IC50为5nM/6nM。
信号通路 Angiogenesis
靶点
LCK
Fyn
Kit
EGFR
Bcr-Abl
IC50
5nM
6nM
~75nM
250nM
1μM
PP1是一种纳摩尔级的Lck和FynT抑制剂，作用于T细胞，抑制anti-CD3诱导的蛋白-酪氨酸激酶活性，
动物实验
包装清单:
产品编号
SC1225-10mM SC1225-5mg SC1225-25mg
－
产品名称 PP1 (Src抑制剂) PP1 (Src抑制剂) PP1 (Src抑制剂)
说明书
包装 10mM×0.2ml
5mg 25mg 1份
达格列净联合双歧杆菌三联活菌对糖尿病性腹泻患者的疗效及血糖水平的影响
DOI：10.16658/ki.1672-4062.2024.01.005达格列净联合双歧杆菌三联活菌对糖尿病性腹泻患者的疗效及血糖水平的影响谢永秀1，张响荣2，张秀林11.宁化县总医院内分泌科，福建三明365400；2.宁化县总医院消化内科，福建三明365400[摘要]目的探讨达格列净联合双歧杆菌三联活菌治疗糖尿病性腹泻的临床效用。
方法选取2021年1月—2022年12月宁化县总医院收治的糖尿病性腹泻患者80例作为研究对象，按照随机数表法分为对照组和观察组，每组40例。
对照组采用二甲双胍+达格列净+蒙脱石散治疗，观察组在此基础上增加双歧杆菌三联活菌治疗。
观察和比较两组患者疗效、血糖水平、肠道菌群。
结果观察组总有效率高于对照组，差异有统计学意义（P<0.05）。
治疗前，两组空腹血糖、餐后2 h血糖、糖化血红蛋白比较，差异无统计学意义（P均>0.05）；治疗后，两组血糖水平低于治疗前，且观察组各指标数值低于对照组，差异有统计学意义（P均<0.05）。
治疗前，两组双歧杆菌、肠杆菌、乳酸杆菌、肠球菌水平比较，差异无统计学意义（P均>0.05）；治疗后，两组双歧杆菌、乳酸杆菌水平高于治疗前，肠杆菌、肠球菌低于治疗前，且观察组双歧杆菌、乳酸杆菌水平高于对照组，肠杆菌、肠球菌水平低于对照组，差异有统计学意义（P均<0.05）。
结论让糖尿病性腹泻患者服用达格列净以及双歧杆菌三联活菌，疗效显著，可调节患者肠道菌群，改善患者血糖水平。
[关键词] 达格列净；双歧杆菌三联活菌；糖尿病性腹泻；疗效；血糖[中图分类号] R587.1 [文献标识码] A [文章编号] 1672-4062（2024）01（a）-0005-04Effect of Dapagliflozin Combined with Bifidobacterium Trifidum on the Efficacy of Diabetic Diarrhea Patients and Blood Glucose LevelsXIE Yongxiu1, ZHANG Xiangrong2, ZHANG Xiulin11.Department of Endocrinology, Ninghua County General Hospital, Sanming, Fujian Province, 365400 China;2.De⁃partment of Gastroenterology, Ninghua County General Hospital, Sanming, Fujian Province, 365400 China[Abstract] Objective To investigate the clinical utility of dapagliflozin combined with bifidobacterium trifidum in the treatment of diabetic diarrhea. Methods A total of 80 patients with diabetic diarrhea admitted to Ninghua County Gen⁃eral Hospital from January 2021 to December 2022 were selected as the study objects, and were divided into control group and observation group according to random number table method, with 40 cases in each group. The control group was treated with metformin + dagaglizin + montmorillonite powder, and the observation group was treated with bifidobacterium triple viable bacteria on this basis. The therapeutic effect, blood glucose level and intestinal flora of the two groups were observed and compared. Results The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). Before treatment, there were no sta⁃tistically significant differences in fasting blood glucose, 2-hour postprandial blood glucose and glycated hemoglobin between the two groups (all P>0.05). After treatment, the blood glucose level of the two groups was lower than before treatment, and the value of each index in the observation group was lower than that in the control group, and the differ⁃ences were statistically significant (all P<0.05). Before treatment, there was no statistically significant difference in the [基金项目]福建中医药大学校管科研课题（XB2021180）[作者简介]谢永秀（1988-），女，本科，主治医师，研究方向为内分泌。
PP1_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PP1 is a potent, and Src family–selective tyrosine kinase inhibitor with IC 50 of 5 and 6 nM for Lck and Fyn, respectively.IC50 & Target: IC50: 5 nM (Lck), 6 nM (Fyn), 250 nM (EGFR), >50 μM (JAK2)[1]In Vitro: PP1 inhibits Lck (IC 50=5 nM) and FynT (IC 50=6 nM) in vitro at concentrations significantly lower than those required to inhibit ZAP–70 (IC 50>100 μM), JAK2 (IC 50>50 μM), the EGFR kinase, and protein kinase A. PP1 inhibits whole cell tyrosinephosphorylation and proliferation in T cells stimulated with anti–CD3 and mitogens. PP1 selectively inhibits IL–2 gene expression over GM–CSF and IL–2R gene induction in human T cells [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Protein A–Sepharose beads (prepared as a 50% (w/v) suspension) are added to the antibody/lysate mixture at 250μL/mL and allowed to incubate for 30 min at 4°C. The beads are then washed twice in 1 mL of lysis buffer and twice in 1 mL of kinase buffer (25 mM HEPES, 3 mM MnCl 2, 5 mM MgCl 2, and 100 μM sodium orthovanadate) and resuspended to 50% (w/v) inkinase buffer. Twenty–five microliters of the bead suspension is added to each well of the enolase–coated 96–well high protein binding plate together with an appropriate concentration of compound and [γ–32P]ATP (25 μL/well of a 200 μCi/mL solution in kinase buffer). After incubation for 20 min at 20°C, 60 μL of boiling 2× solubilization buffer containing 10 mM ATP is added to the assay wells to terminate the reactions. Thirty microliters of the samples is removed from the wells, boiled for 5 min, and run on a7.5% SDS–polyacrylamide gel. The gels are subsequently dried and exposed to Kodak X–AR film. For quantitation, films are scanned using a Molecular Dynamics laser scanner, and the optical density of the major substrate band, enolase p46, is determined.Concentrations of compound that causes 50% inhibition of enolase phosphorylation (IC50) are determined from a plot of the density versus concentration of compound. In companion experiments for measuring the activity of compounds against Lck, the assay plate is washed with two wash cycles on a Skatron harvester using 50 mM EDTA, 1 mM ATP. Scintillation fluid (100 μL) is then added to the wells, and P incorporation is measured using a Pharmacia Biotech micro–β–counter. Concentrations of compound that causes 50% inhibition of enzyme activity (IC 50) are determined from a plot of the percent inhibition of enzyme activity versus concentration of compound [1]. ?Cell Assay: PP1 is dissolved in DMSO and stored, and then diluted with appropriate medium before use [2]. [1]Inhibition ofanti–CD3–stimulated tyrosine phosphorylation in purified human peripheral blood T cells is measured as follows. All incubations are carried out at 37°C in an Eppendorf Thermomixer 5436 at a mixing setting of 11. Cells (1×106 in 100 μL of RPMI 1640 medium) are incubated for 15 min with drug prior to a 6–min incubation with 1 μg of anti–CD3/mL (anti–leu4, 100 μg/mL). The final volume of thereaction is 115 μL. Reactions are terminated by the addition of 57.5 μL of 3× solubilization buffer incubated at 100°C prior to its addition. Samples are mixed, boiled for 5 min, and stored at –70°C. Western blots of these cell lysates, run on 10%SDS–polyacrylamide gels, are probed with a polyclonal anti–phosphotyrosine antibody, and immune complexes are detected with I–labeled protein A (ICN). For quantitation, films are scanned using a Molecular Dynamics laser scanner, and the optical densities ofProduct Name:PP1Cat. No.:HY-13804CAS No.:172889-26-8Molecular Formula:C 16H 19N 5Molecular Weight:281.36Target:Src Pathway:Protein Tyrosine Kinase/RTK Solubility:DMSO: ≥ 28 mg/mL (Need ultrasonic)the major substrate band, p70, are quantitated in the presence of anti–CD3 (in the presence and absence of drug). Percent inhibition is calculated as follows: (1–(p70 optical density units in presence of drug/p70 units in absence of drug))×100. IC50 equals the concentration of compound at which 50% inhibition is measured[1].References:[1]. Hanke JH, et al. Discovery of a novel, potent, and Src family–selective tyrosine kinase inhibitor. Study of Lck– and FynT–dependent T cell activation. J Biol Chem. 1996 Jan 12;271(2):695–701.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
二甲双胍联合阿卡波糖在2型糖尿病患者中的应用效果分析
DOI：10.16658/ki.1672-4062.2023.23.081二甲双胍联合阿卡波糖在2型糖尿病患者中的应用效果分析方信英平潭综合实验区中医院，福建福州350400[摘要]目的研讨二甲双胍联合阿卡波糖对2型糖尿病（type 2 diabetes， T2DM）患者的临床应用效果。
方法选取2022年4月—2023年4月经平潭综合实验区中医院确诊为T2DM的120例患者为研究对象，依据随机数表法均等纳入2组，各60例。
对照组单纯予以二甲双胍降糖治疗，观察组基于对照组用药条件联合阿卡波糖治疗，比较两组治疗前后的糖脂代谢指标、血胰岛素、机体氧化应激状况以及治疗安全性。
结果治疗后，观察组各项糖脂代谢指标空腹血糖、餐后2 h血糖以及三酰甘油检测值均低于对照组，差异有统计学意义（P<0.05）。
治疗后，观察组空腹及餐后2 h胰岛素检测值均低于对照组，差异有统计学意义（P<0.05）。
治疗后，观察组脂质过氧化氢、丙二醛检测值较对照组更低，超氧化物歧化酶检测值更高，差异有统计学意义（P< 0.001）。
两组发生药物不良反应的患者占比（10.00% vs 6.67%）对比，差异无统计学意义（χ2=0.436，P= 0.508）。
结论二甲双胍与阿卡波糖配伍用药能够更好地调节T2DM患者的糖脂代谢及血胰岛素水平，有效减轻机体氧化应激反应，且不增加药物不良反应发生。
[关键词] 2型糖尿病；二甲双胍；阿卡波糖；糖脂代谢[中图分类号] R59 [文献标识码] A [文章编号] 1672-4062（2023）12（a）-0081-04Effect of Metformin Combined with Acarbose in Patients with Type 2 Dia⁃betes MellitusFANG XinyingPingtan Comprehensive Experimental Area Hospital of Traditional Chinese Medicine, Pingtan, Fujian Province, 350400 China[Abstract] Objective To study the clinical effect of metformin combined with acarbose in patients with type 2 diabe‐tes mellitus (T2DM). Methods A total of 120 patients diagnosed with T2DM in the Traditional Chinese Medicine Hos‐pital of Pingtan Comprehensive Experimental Area from April 2022 to April 2023 were selected as the study objects and equally included in the two groups according to the random number table method, with 60 cases in each group. The control group was treated with metformin alone, and the observation group was treated with acarbose based on the medication conditions of the control group. The glucose and lipid metabolism indexes, blood insulin, oxidative stress and treatment safety were compared between the two groups before and after treatment. Results After treatment, the glucose and lipid metabolism indexes fasting blood glucose, 2-hour postprandial blood glucose and triglyceride in the observation group were lower than those of the control group, and the differences were statistically significant (P<0.05). After treatment, the fasting and 2 h postprandial insulin values of the observation group were lower than those of the control group, and the differences were statistically significant (P<0.05). After treatment, the levels of lipid hydrogen peroxide and malondialdehyde in the observation group were lower than those in the control group, the detection value of superoxide dismutase was higher, and the differences were statistically significant (P<0.001).There was no signifi‐cant difference in the proportion of patients with adverse drug reactions between the two groups (10.00% vs 6.67%) (χ2=0.436, P=0.508). Conclusion The combination of metformin and acarbose can better regulate the glucose and [作者简介]方信英（1977-），女，本科，副主任药师，研究方向为2型糖尿病。
b-AP15_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:b–AP15 is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14.IC50 & Target: UCHL5/Usp14[1]In Vitro: Purified 19S proteasomes (5 nM) are treated with indicated concentrations of b–AP15 and DUB activity is determined by detectionof Ub–AMC cleavage. The IC 50 value (2.1±0.411 μM) is determined from log concentration curves in Graph Pad Prism using non linear regression analysis. b–AP15 as a previously unidentified class of proteasome inhibitor that abrogates thedeubiquitinating activity of the 19S regulatory particle. b–AP15 inhibited the activity of two 19S regulatory–particle–associated deubiquitinases, ubiquitin C–terminal hydrolase 5 (UCHL5) and ubiquitin–specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b–AP15 induced tumor cell apoptosis that is insensitive to TP53 status and overexpression of the apoptosisinhibitor BCL2[1]. The ability of b–AP15 is determined to inhibit proteasome deubiquitinase activity using Ub–AMC as the substrate.An IC 50 of 16.8±2.8 μM is observed [2]. b–AP15 is a specific USP14 and UCHL5 inhibitor, which blocks growth and induces apoptosis in MM cells [3].In Vivo: b–AP15 (2.5 mg/kg) inhibits tumor growth in syngenic mice models with less frequent administration schedules. We administered b–AP15 to C57BL/6J mice with Lewis lung carcinomas (LLCs) using a 2–d–on, 2–d–off schedule and to BALB/c mice with orthotopic breast carcinoma (4T1) using a 1–d–on, 3–d–off schedule. b–AP15 significantly inhibited tumor growth in both models, with T/C=0.16 (P≤0.01) for the C57BL/6J mice and T/C=0.25 (P≤0.001) for the BALB/c mice. A reduction in the number of pulmonary metastases also is observed in the group of mice with 4T1 breast carcinomas treated with b–AP15[1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]For deubiquitinase inhibition assays, 19S regulatory particle (5 nM), 26S (5 nM) UCH–L1 (5 nM), UCH–L3 (0.3 nM),USP2CD (5 nM) USP7CD (5 nM) USP8CD (5 nM) or BAP1 (5 nM) is incubated with DMSO or b–AP15 and monitored the cleavage of ubiquitin–AMC (1,000 nM) using a Wallac VICTOR Multilabel counter or a Tecan Infinite M1000 equipped with 380 nm excitation and 460 nm emission filters [1].Cell Assay: b–AP15 is dissolved in DMSO and stored, and then diluted with appropriate medium before use [2]. [2]Cell viability is monitored by either the fluorometric microculture cytotoxicity assay or the MTT assay. For the MTT assay, cells are seeded into 96–well flat–bottomed plates overnight and exposed to drugs, using DMSO as the control. At the end of incubations, 10 μl of a stock solution of 5 mg/mL MTT is added into each well, and the plates are incubated 4 hours at 37°C. Formazan crystals are dissolved with 100 μL 10% SDS/10 mM HCl solution overnight at 37°C. Absorbance is measured using an enzyme–linkedimmunosorbent assay (ELISA) plate reader at 590 nm [2].Animal Administration: b–AP15 is dissolved it in Cremophor EL and polyethylene glycol 400 (1:1) by heating to reach aworking concentration of 2 mg/mL. Working stock is 1:10 diluted in 0.9% saline immediately before injection (Mice)[1].[1]Mice [1]For the squamous carcinoma model, 1×106 FaDu cells are subcutaneously injected into the right rear flank of female SCIDProduct Name:b–AP15Cat. No.:HY-13989CAS No.:1009817-63-3Molecular Formula:C 22H 17N 3O 6Molecular Weight:419.39Target:Deubiquitinase Pathway:Cell Cycle/DNA Damage Solubility:DMSO: ≥ 44 mg/mLmice. Tumor growth is measured by the formula length×width2×0.44. When tumors have grown to a size of approximately 200 mm3 (defined as day 0), mice are randomized to receive either vehicle (n=10) or b–AP15 (n=15) at 5 mg per kg of body weight by daily subcutaneous injection. For the colon carcinoma model, we subcutaneously injected 2.5 × 106 HCT–116 colon carcinoma cells overexpressing Bcl2 into the right flank of female nude mice. We treated mice with 5 mg of b–AP15 per kg of body weight by intraperitoneal injection. For the lung carcinoma model, we subcutaneously injected 2×105 LLC cells into the right rear flank of female C57/B6 mice. When tumors had grown to a size of approximately 50 mm3 (defined as day 0), we randomized mice to receive either vehicle (n=4) or b–AP15 (n=4) at 5 mg per kg of body weight intraperitoneally, with a treatment cycle consisting of 2 d of treatment followed by 2 d of rest (2 d on, 2 d off) for 2 weeks.References:[1]. D'Arcy P, et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011 Nov 6;17(12):1636–40.[2]. Wang X, et al. The 19S Deubiquitinase Inhibitor b–AP15 is Enriched in Cells and Elicits Rapid Commitment to Cell Death. Mol Pharmacol. 2014 Jun;85(6):932–45.[3]. Tian Z, et al. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30;123(5):706–16.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
PP1_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :PP1Catalog No. :HY-13804CAS No. :172889-26-81.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 3), H3012.2 GHS Label elements, including precautionary statementsPictogramSignal word DangerHazard statement(s)H301 Toxic if swallowed.Precautionary statement(s)P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.P321 Specific treatment (see supplemental first aid instructions on this label).P330 Rinse mouth.P405 Store locked up.P501 Dispose of contents/ container to an approved waste disposal plant.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:AGL 1872; EI 275; PP 1; PP⁻1Formula:C16H19N5Molecular Weight:281.36CAS No. :172889-26-84. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaustventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)UN number: 2811Class: 6.1Packing group: IIIProper shipping name: Toxic solids, organic, n.o.s. (PP1)Marine pollutant: NoPoison Inhalation Hazard: NoIMDGUN number: 2811Class: 6.1Packing group: IIIEMS-No: F-A, S-AProper shipping name: TOXIC SOLID, ORGANIC, N.O.S. (PP1)Marine pollutant: NoIATAUN number: 2811Class: 6.1Packing group: IIIProper shipping name: Toxic solid, organic, n.o.s. (PP1)15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
PYR-41_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PYR–41 is a specific and cell permeable inhibitor of ubiquitin–activating enzyme E1 with an IC 50 of < 10 μM, with no or little activity at E2.IC50 & Target: IC50: < 10 μM (E1)In Vitro: PYR–41 increases total sumoylation in cells in addition to blocking ubiquitylation. PYR–41 attenuates cytokine–mediated nuclear factor–κB activation. PYR–41 also prevents the downstream ubiquitylation and proteasomal degradation of IκBα.Furthermore, PYR–41 inhibits degradation of p53 and activates the transcriptional activity of this tumor suppressor [1]. PYR–41(50 μM) promotes accumulation of ubiquitinated proteins. PYR–41 causes a concentration–dependent (10–50 μM) decline in DUB activity in Z138 cells after 4 h. PYR–41 potently inhibits USP5 DUB activity, even at the lowest concentration (10 μM). PYR–41potently (10–50 μM) inhibits the activity of various DUBs, determined to represent USP9x, USP5, USP14, UCH37 and UCH–L3.Co–treatment of Z138 cells with DTT and PYR–41 completely abolishes the accumulation of ubiquitinated proteins [2].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Rabbit or mouse E1 (apper 250 ng) is incubated with 32P–ubiquitin in 1× reaction buffer [50 mM Tris (pH 7.4), 0.2mM ATP, 0.5 mM MgCl 2] at room temperature for 15 min. In some experiments, the His–tagged mouse E1 is bound to TALON cobalt affinity resin before carrying out incubations and reactions. Mouse E1 and 32P–ubiquitin are added to the beads in 1× reaction bufferand incubated as for E1 reactions. Samples are heated in nonreducing SDS–PAGE sample buffer and resolved by SDS–PAGE.Thioesters with ubiquitin are visualized by Storm PhosphoImager.References:[1]. Yang Y, et al. Inhibitors of ubiquitin–activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472–81.[2]. Kapuria V, et al. Protein cross–linking as a novel mechanism of action of a ubiquitin–activating enzyme inhibitor with anti–tumor activity. Biochem Pharmacol. 2011 Aug 15;82(4):341–9.Product Name:PYR–41Cat. No.:HY-13296CAS No.:418805-02-4Molecular Formula:C 17H 13N 3O 7Molecular Weight:371.30Target:E1/E2/E3 Enzyme Pathway:Metabolic Enzyme/Protease Solubility:DMSO: ≥ 46 mg/mLCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@ Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
阿卡波糖片与二甲双胍治疗2型糖尿病的临床效果及药物不良反应分析
阿卡波糖片与二甲双胍治疗2型糖尿病的临床效果及药物不良反应分析李剑珠，宋宏，沈燕萍莆田学院附属医院药剂科，福建莆田351100[摘要]目的探究阿卡波糖片与二甲双胍治疗2型糖尿病（diabetes mellitus type 2， T2DM）的临床效果及药物不良反应分析。
方法选取2020年10月—2022年10月于莆田市荔城区莆田学院附属医院进行治疗的86例T2DM患者作为研究对象，采用信封法随机分为二甲双胍组与阿卡波糖片组，每组43例，分别予以二甲双胍与阿卡波糖片治疗。
比较两组血糖水平、不良反应发生情况以及生活质量。
结果治疗后，阿卡波糖片组空腹血糖、餐后2 h血糖、糖化血红蛋白水平均低于二甲双胍组，差异有统计学意义（P<0.05）。
两组不良反应发生率比较，差异无统计学意义（P>0.05）。
治疗后，阿卡波糖片组世界卫生组织生活质量测定简表中的躯体、社会、环境、心理、综合维度评分均高于二甲双胍组，差异有统计学意义（P<0.05）。
结论针对T2DM患者，阿卡波糖片与二甲双胍疗效确切，安全性相当，但阿卡波糖片相对能更好地控制患者血糖，患者的生活质量更高。
[关键词] 2型糖尿病；阿卡波糖片；二甲双胍；临床效果；安全性；生活质量[中图分类号] R587 [文献标识码] A [文章编号] 1672-4062（2023）11（b）-0077-04Clinical Effects and Adverse Drug Reactions of Acarbose Tablets and Met⁃formin in the Treatment of Type 2 Diabetes MellitusLI Jianzhu, SONG Hong, SHEN YanpingDepartment of Pharmacy, the Affiliated Hospital of Putian University, Putian, Fujian Province, 351100 China[Abstract] Objective To explore the clinical effects and adverse drug reactions of Acarbose tablets and Metformin in the treatment of type 2 diabetes mellitus (T2DM). Methods A total of 86 T2DM patients treated in the Affiliated Hos⁃pital of Putian University, Licheng District, Putian City from October 2020 to October 2022 were selected as the study objects. They were randomly divided into Metformin group and Acarbose tablet group by envelope method, with 43 cases in each group receiving Metformin andAcarbose tablet treatment, respectively. Blood glucose levels, adverse re⁃actions and quality of life were compared between the two groups. Results After treatment, fasting blood glucose, 2 hours postprandial blood glucose and glycated hemoglobin levels in Acarbose tablet group were lower than those in Metfor⁃min group, and the differences were statistically significant (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). After treatment, the scores of physical, social, environmental, psychological and comprehensive dimensions of Acarbose tablet group were higher than those of Met⁃formin group, and the differences were statistically significant (P<0.05). Conclusion For T2DM patients, Acarbose tab⁃lets have the same efficacy and safety as Metformin, but Acarbose tablets can better control patients' blood glucose and improve patients' quality of life.[Key words] Type 2 diabetes; Acarbose tablets; Metformin; Clinical effect; Security; Quality of life糖尿病是一种因胰岛素分泌不足而导致的糖类代谢紊乱疾病，患者一旦发病，则需要终身服药控制血糖。
本刊参考文献著录格式
364中国艾滋病性病2021年4月第27卷第4期Chin J AIDS STD Vo丨.27 No.4 Apr 2021[5] ANGLIN MD, BURKE C, PERROCHET B, et al. History ofthe methamphetamine problem[j], J Psychoactive Drugs,2000,32(2)：137-141.[6] CHENG T, JOHNSTON C, KERR T, et al. Substance usepatterns and unprotected sex among street-involved youth in aCanadian setting：a prospective cohort study ^J. BMC PublicHealth,2016(16)：4.[7] BAILEY SL, GAO W, CLARK DB. Diary study of substanceuse and unsafe sex among adolescents with substance usedisorders[ J]. J Adolesc Health,2006,38( 3) ：213-297.[8] DUNN M, DAY C, BRUNO R, et al. Sexual and injecting riskbehaviours among regular ecstasy users [J]. Addict Behav, 2010,35(2)：157-160.[9] ZUCKERMAN MD, BOYER EW. HIV and club drugs inemerging adulthood [J]. Curr Opin Pediatr, 2012, 24 (2)：219-224.[10]郭巍，曲书泉，丁正伟，等.中国1995 — 2009年吸毒者艾滋病毒感染和梅毒流行趋势分析[J].中华流行病学杂志，2010,31(6)：666-669.[11] BAO YP, LIU ZM. Systematic review of HIV and HCVinfection among drug users in China[j]. Int J STD AIDS,2009,20(6)： 399-405.[12]葛琳，李东民，李培龙，等.2010-2015年中国艾滋病哨点监测人群HIV、梅毒和HCV感染状况分析[J].疾病监测，2017,32(2)：111-117.[13]许艳，王璐.国内外M0岁年龄组人群艾滋病流行特征及危险因素[J].中华流行病学杂志，2011,32(11): 1166-1169.[14] ZHUANG X, LIANG Y, CHOW EP, et al. HIV and HCVprevalence among entrants to methadone maintenance treatmentclinics in China：a systematic review and meta-analysis LJ]-BMC Infect Dis,2012( 12) ： 130.[15] BAO Y, LARNEY S, PEACOCK A, et al. Prevalence of HIV,HCV and HBV infection and sociodemographic characteristicsof people who inject drugs in China：A systematic review andmeta-analysis[j]. Int J Drug Policy,2019( 70)：87-93.L16] WANG BX, ZHANG L, WANG YJ, et al. Epidemiology of syphilis infection among drug users at methadone maintenancetreatment clinics in China：systematic review and meta-analysis[J]. Int J STD AIDS,2014,25(8) ：550-558.[17] ZHANG L, CHOW EP, JING J, et al. HIV prevalence inChina：integration of surveillance data and a systematic review[J ]. Lancet Infect Dis, 2013,13 (11) ： 955-963.[18] BAO YP, LIU ZM, LU L. Review of HIV and HCV infectionamong drug users in China [j]. Current opinion in psychiatry2010,23(3)：187-194.[19] ZHANG L, ZHANG D, CHEN W, et al. High prevalence ofHIV, HCV and tuberculosis and associated risk behavioursamong new entrants of methadone maintenance treatment clinicsin Guangdong Province, China[j]. PLoS One, 2013,8( 10) ：e76931. [20] LUO W, WU Z, POUNDSTONE K, et al. Needle and syringeexchange programmes and prevalence of HIV infection amongintravenous drug users in China [ J ]. Addiction ,2015,110 (Suppll)：61-67.[21 ]陈雯，凌莉，何群，等.广东省社区美沙酮维持治疗项目绩效评价与政策建议[J].中国卫生政策研究，2010,3(3) :39-44.[22] WANG L, GUO W, LI D, et al. HIV epidemic among drugusers in China：1995-2011 [J]. Addiction (Abingdon,England), 2015,110 Suppl l(l)：20-28.[23]樊盼英，汪宁.新型毒品滥用对艾滋病流行的影响[J].中华流行病学杂志，2010，31 (3): 340-343.[24]葛琳，崔岩，王璐，等.2012年全国艾滋病哨点吸毒人群血清学和性行为特征分析[J].中华流行病学杂志，2014, 35 (2):121-123.[25] KOESTERS SC, ROGERS PD, RAJASINGHAM CR. MDMA('ecstasy') and other 'club drugs'. The new epidemic [J]. PediatrClin North Am, 2002,49( 2) ： 415-433.1言息本刊参考文献著录格式凡文内引用他人的结果或结论，均应标注并在文末列出参考文献，只限亲自阅读的近期公开发表过的，未公开发表的文献不列入。
1-NM-PP1_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:1–NM–PP1 inhibits Cdk7 recovered from the mutant, but not the wild–type cells with an IC 50 of ~50 nM with either substrate.IC50 & Target: CDK7[1]In Vitro: Cdk7 from Cdk7as/as or Cdk7+/+ cells is immunoprecipitated and tested its kinase activity towards both a Pol IICTD–containing fusion protein (GST–CTD) and human Cdk2. Cdk7 recovered from the mutant, but not the wild–type, cells is inhibited by 1–NM–PP1 (1–NMPP1), with an IC 50 of ~50 nM with either substrate. Replacement of wild–type Cdk7 with Cdk7as/as also rendered growth of HCT116 cells sensitive to 1–NM–PP1. In the absence of 1–NM–PP1, the wild–type and Cdk7as/as cells had population doubling times of ~17.9 and ~20.2 h, respectively, with similar cell–cycle distributions in asynchronous culture, indicating minimal impairment of Cdk7 function by the F91G mutation per se. The homozygous Cdk7as/as cells are sensitive to 1–NM–PP1,however, with an IC 50 ~100 nM measured by cell viability (MTT) assays performed after 96 h of 1–NM–PP1 exposure. In contrast,wild–type HCT116 cells are resistant to 10 μM 1–NM–PP1. Addition of 10 μM 1–NM–PP1 retards G1/S progression by the mutant but not the wild–type cells. When added simultaneously with serum to the Cdk7as/as cells, 1–NM–PP1 prevents any progression into S phase in the next 15 h. After 24 h, there is evidence of progression into S–phase by a fraction of Cdk7as/as cells released from serum starvation directly into medium containing 1–NM–PP1, while a fraction remained in G1. The addition of 1–NM–PP1 3 h or 6 h after serum addition delays S–phase entry by ~7 h or by ~3 h, respectively [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Immunoblotting and immunoprecipitation, and kinase assays of immune complexes, are carried out. To measure Cdk1/cyclin B assembly, extracts (200 μg total protein) from cells in mitosis or G2 are pre–incubated with 2 μM 1–NM–PP1 or DMSO, then added 500 ng purified cyclin B1, amino–terminally tagged with hexahistidine and the Myc epitope, and anATP–regenerating system. Where indicated, incubations are supplemented with 400 ng purified Csk1 or 600 ng wild–type or analog–sensitive, T–loop–phosphorylated Cdk7/cyclin H/Mat1 complex. After 90 min at room temperature, Myc–cyclin B and associated proteins are immunoprecipitated with anti–Myc antibodies and immune complexes are subjected to immunoblotting,with anti–Myc and anti–Cdk1 antibodies, and tested for histone H1 kinase activity [1].Cell Assay: 1–NM–PP1 (1–NMPP1) is dissolved in DMSO and stored, and then diluted with appropriate media beforeuse [1].[1]Wild–type or Cdk7as/as HCT116 cells are synchronized by incubation in serum–free medium for 48 h and released into medium containing 10% fetal calf serum. Synchronization with thymidine or nocodazole, and analysis of cell–cycle distribution by flow cytometry, are performed. Cell viability is measured by MTT assay [1].References:[1]. Larochelle S, et al. Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells. Mol Cell.Product Name:1–NM–PP1Cat. No.:HY-13942CAS No.:221244-14-0Molecular Formula:C 20H 21N 5Molecular Weight:331.41Target:CDK Pathway:Cell Cycle/DNA Damage Solubility:DMSO: 27.5 mg/mL2007 Mar 23;25(6):839–50.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
盐酸文拉法辛缓释片治疗抑郁焦虑共病的临床效果评价
*论著*盐酸文拉法辛缓释片治疗抑郁焦虑共病的临床效果评价刘霞,庄晓华山东省临沂市精神卫生中心，山东临沂276005摘要目的对盐酸文拉法辛缓释片治疗抑郁焦虑共病的临床效果进行评价分析。
方法选择2019年1-12月在该院住院的80例抑郁焦虑共病患者作为临床研究对象，按照随机原则，将患者分为实验组和对照组，每组40例。
实验组患者采用盐酸文拉法辛缓释片进行治疗,对照组患者采用盐酸帕罗西汀片进行治疗，对两组患者的临床治疗效果等进行比较和分析。
结果经过为期8周的治疗，实验组患者临床治疗有效率为95.0%，明显高于对照组77.50%,差异有统计学意义(x2=5.165,!<0.05)o对两组患者治疗前后的HAMD&HAMA评分情况进行比较，在治疗前，两组评分对比，差异无统计学意义(P>0.05)o经过为期8周的治疗，实验组和对照组的HAMD&HAMA评分对比治疗前均明显降低，差异有统计学意义(！<0.05)。
在治疗4周末，实验组显著低于对照组HAMD&HAMA评分情况，差异有统计学意义(！<0.05)。
在治疗8周末，实验组显于对照组HAMD&HAMA评分情况，差异有统计学意义(！<0.05)。
情况来看，实验组率为17.50%，明显低于对照组(37.50%)，差异有统计学意义(！<0.05)。
结对抑郁焦虑共病患者的治疗，使用盐酸文拉法辛缓释片能够有效提升临床治疗有效率，改善HAMD&HAMA评分水平，降低不良反应发生率，具有良好的临床治疗效果。
关键词盐酸文拉法辛缓释片；抑郁焦虑共病；临床疗效中图分类号R749文献标志码A doil0.11966/j.issn.2095-994X.2021.07.02.01Evaluation of the Clinical Effect of Venlafaxine Hydrochloride Sustained-release Tablets in the Treatment of Comorbid Depression and AnxietyLIU Xia,ZHUANG Xiao-huaLinyi Mental Health Center,Linyi,Shandong Province,276005ChinaAbstract Objective To evaluate and analyze the clinical effects of venlafaxine hydrochloride sustained-release tablets in the treatment of comorbid depression and anxiety.Methods From January to December2019,80patients with comorbid depression and anxiety who were hospitalized in the hospital were selected as clinical research objects.According to the principle of randomization,the patients were divided into experimental and control groups,each with40cases.Patients in the experimental group were treated with venlafaxine hydrochloride sustained-release tablets,and patients in the control group were treated with paroxetine hydrochloride tablets.The clinical treatment effects of the two groups of patients were compared and analyzed.Results After8weeks of treatment,the clinical treatment effective rate of the experimental group was95.00%,which was significantly higher than that of the control group77.50%, the difference was statistically significant(x"=5.165,!<0.05).The HAMD and HAMA scores of the two groups of patients before and after treatment were compared.Before treatment,the difference was not statistically significant(!>0.05).After8weeks of treatment, the HAMD and HAMA scores of the experimental group and the control group were significantly reduced,the difference were statistically significant(!<0.05).At the4th weekend of treatment,the experimental group were significantly lower than the control group's HAMD and HAMA scores,the difference were statistically significant(!<0.05).At the8th weekend of treatment,the experimental group were significantly lower than the control group's HAMD and HAMA scores,the difference were statistically significant(!<0.05). In terms of the occurrence of adverse reactions,the incidence of adverse reactions in the experimental group was17.50%,which was收稿日期：2021—01—06；修回日期：2021-01-25作者简介：刘霞(19+4-),女，本科，主治医师，研究方向为临床精神医学&significantly lower than that in the control group37.50%,the difference was statistically significant(!<0.05).Conclusion For the treatment of patients with comorbid depression and anxiety,the use of venlafaxine hydrochloride sustained-release tablets can effectively improve the clinical treatment efficiency,improve the HAMD and HAMA score levels,reduce the incidence of adverse reactions,and have a good clinical treatment effect.Key words Venlafaxine hydrochloride sustained-release tablets;Depression and anxiety comorbidity;Clinical efficacy在精神科疾病的临床实践中，抑郁焦虑共病是一种较为严重的精神障碍疾病。
Keap1
非小细胞肺癌(non-small cell lung cancer，NSCLC)发病率占据肺癌的75%~80%。
肿瘤细胞进展快且易扩散转移，临床常采用手术、放化疗等进行治疗，但5年生存率低于60%[1-2]。
氧化应激是由活性氧(ROS)生成量增加所致，ROS积累可诱导肺癌细胞凋亡，清除ROS 可阻止癌细胞凋亡，即肺癌细胞存活依赖于癌细胞自身抗氧化能力[3]。
Kelch样环氧氯丙烷相关蛋白-1 (kelch-like epichlorohydrin-associated protein-1，Keap1)/核因子E2相关因子2(nuclear factor E2related factor 2，Nrf2)信号通路在癌症中发挥重要调控作用，氧化应激可激活Keap1，促使Keap1-Nrf2复合物裂解，Nrf2转移至细胞核内，可激活下游靶基因表达，参与肺癌发生发展过程[4]。
Nrf2可维持氧化还原稳态，ROS侵袭细胞时，Nrf2可进入细胞核，结合抗氧化反应元件(ARE)转录编码各种抗氧化蛋白、代谢酶基因，抑制氧化应激反应[5-6]。
目前氧化应激、Keap1/Nrf2信号通路在NSCLC发生过程中的机制尚未明确。
基于此，本研究尝试分析Keap1/Nrf2信号通路与临床病理参数、氧化应激指标的相关性，探讨其在NSCLC氧化应激机制中的作用，为临床研制新药提供参考依据。
1资料与方法1.1一般资料选取2017年4月至2020年4月郑州市第三人民医院收治的100例NSCLC患者为研究对象。
纳入标准：符合NSCLC诊断标准[7]；术前未接受放化疗、免疫治疗者；预计生存期≥6个月；符合手术适应证、禁忌证；Karnofsky功能状态评分≥70分；签署知情同意书。
排除标准：合并凝血功能障碍、肝肾功能障碍、其他恶性肿瘤者；伴有急/慢性感染者；伴有精神疾病者；既往腹部相关外科手术史者。
所有患者均行肺癌根治性切除术，术中收集癌组织、癌旁组织(距离癌组织5cm范围内正常组织)，其中男性63例，女性37例；年龄46~67岁，平均(56.32±3.16)岁；体质量指数(BMI)17~30kg/m2，平均(23.16±2.03)kg/m2；病理类型：鳞癌58例、腺癌42例；病理分级[8]：Ⅰ~Ⅱ级51例、Ⅲ级49例；T分期[9]：T1~T253例、T3~T447例；N分期：N055例、N1~N245例。
2013年6月20日发布最新影响因子IF_完整版
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6190MUCOSAL IMMUNOL1933-021*******.119 1.65767 3826INT J EPIDEMIOL0300-577114451 6.9827.001 3.281128 4205J AM ACAD CHILD PSY0890-856716470 6.977.148 2.0196 6223NANOMED-NANOTECHNOL1549-96343097 6.937.647 1.263160 2228CURR TOP DEV BIOL0070-21532246 6.912 6.4670.76242 6685P IEEE0018-921918840 6.9117.6940.697195 3200GLOBAL CHANGE BIOL1354-101318398 6.917.819 1.3297 6534OCEANOGR MAR BIOL0078-32182142 6.9099.8790.56 5139J NEUROSCI0270-6474160915 6.9087.8690.9781668 3362HUM BRAIN MAPP1065-947113379 6.8787.032 1.451226 3398HYPERTENSION0194-911X32323 6.873 6.984 1.588342 6518OBES REV1467-78815154 6.877.021 1.436101 6008METAB ENG1096-71762855 6.859 6.696 1.34772 1864CLIN PHARMACOL THER0009-923614263 6.846 6.349 1.995200 1627CEREB CORTEX1047-321121409 6.8287.463 2.05258 3224GREEN CHEM1463-926215554 6.828 6.992 1.269449 6929PHYS TODAY0031-92283738 6.762 5.263 1.51437 275ADV ORGANOMET CHEM0065-3055841 6.758.94103 6949PHYSIOLOGY1548-92132500 6.758.388 1.13829 6407NEW PHYTOL0028-646X26842 6.736 6.888 1.373378 929ASTROPHYS J0004-637X191940 6.733 5.945 2.0473075 1764CIRC-CARDIOVASC GENE1942-325X1641 6.728 6.398 1.17182 6921PHYS REV X2160-3308414 6.711 6.737 2.22571 6158MOL ONCOL1574-78911193 6.701 6.3790.91760 1768CIRC-HEART FAIL1941-32892007 6.684 6.67 1.41993 1309BMC MED1741-70152691 6.679 6.413 1.275109 1820CLIN GASTROENTEROL H1542-35658295 6.648 6.108 1.458179 6561ONCOTARGET1949-25531450 6.636 6.636 1.316114 2177CURR OPIN COLLOID IN1359-02944670 6.6297.0360.88443 2862EXPERT REV MOL MED1462-39941734 6.6230.78919 1417BRIT J PSYCHIAT0007-125021472 6.6067.112 1.872117 1019B AM METEOROL SOC0003-000711821 6.5917.704 2.48778 5280J PHYS CHEM LETT1948-71858575 6.585 6.651 1.301632 6902PHYS LIFE REV1571-0645659 6.583 6.699.45511 6990PLANT J0960-741232497 6.5827.113 1.5333456997PLANT PHYSIOL0032-088962407 6.5557.084 1.313469 5605JACC-CARDIOVASC INTE1936-87983378 6.552 6.834 1.603126 2396DRUG DISCOV TODAY1359-64468855 6.551 6.89 1.177158 271ADV MICROB PHYSIOL0065-29111006 6.545 6.267 1.25 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非布司他联合二甲双胍治疗2型糖尿病伴高尿酸血症对尿酸水平及血糖的影响
DOI：10.16658/ki.1672-4062.2023.22.110非布司他联合二甲双胍治疗2型糖尿病伴高尿酸血症对尿酸水平及血糖的影响张艺羡，杨智敏，陈颖福建医科大学附属漳州市医院药学部，福建漳州363000[摘要]目的探究应用非布司他联合二甲双胍治疗2型糖尿病（diabetes mellitus type 2, T2DM）伴高尿酸血症（hyperuricemia, HUA）患者对尿酸水平和血糖的影响。
方法选取2022年1—11月福建医科大学附属漳州市医院接受治疗的86例T2DM合并HUA患者作为研究对象，并按随机数表法分成对照组（43例）和联合组（43例）。
对照组口服二甲双胍治疗，联合组采用二甲双胍结合非布司他治疗。
比较两组治疗效果、尿酸水平、血糖水平和不良反应发生率的变化。
结果联合组治疗后的总有效率95.35%高于对照组的79.07%，差异有统计学意义（P<0.05）；治疗后，两组血尿酸、血尿素氮、空腹血糖、餐后2 h血糖、糖化血红蛋白水平均低于本组治疗前，尿pH值高于本组治疗前，差异有统计学意义（P<0.05）；联合组治疗后的不良反应发生率为9.30%低于对照组的25.58%，差异有统计学意义（P<0.05）。
结论非布司他联合二甲双胍对T2DM合并HUA患者的疗效显著，能降低患者的尿酸和血糖水平，减少发生不良反应。
[关键词] 非布司他；二甲双胍；2型糖尿病；高尿酸血症；尿酸；血糖[中图分类号] R59 [文献标识码] A [文章编号] 1672-4062（2023）11（b）-0110-04Effect of Febuxostat Combined with Metformin in the Treatment of Type2 Diabetes Mellitus with Hyperuricemia on Uric Acid Levels and BloodGlucoseZHANG Yixian, YANG Zhimin, CHEN YingDepartment of Pharmacy, Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou, Fujian Province, 363000 China[Abstract] Objective To investigate the effects of the application of febuxostat combined with metformin in the treat⁃ment of type 2 diabetes mellitus type 2 (T2DM) with hyperuricemia (HUA) patients on uric acid level and blood glu⁃cose. Methods A total of 86 T2DM patients with HUA who were treated in Zhangzhou Municipal Hospital Affiliated to Fujian Medical University from January to November 2022 were selected as the research objects, and were divided into control group (43 cases) and combined group (43 cases) according to the random number table method. The con⁃trol group was treated with metformin, and the combined group was treated with metformin combined with febuxostat. The therapeutic effect, uric acid level, blood glucose level and the incidence of adverse reactions were compared be⁃tween the two groups.Results The total effective rate of the combined group was 95.35%, which was higher than 79.07% of the control group, and the difference was statistically significant (P<0.05). After treatment, the levels of blood uric acid, blood urea nitrogen, fasting plasma glucose, postprandial 2 h blood glucose and glycosylated hemoglo⁃bin in the two groups were lower than those before treatment, and the urine pH value was higher than that before treat⁃ment, and the differences were statistically significant (P<0.05). The incidence of adverse reactions after treatment in the combined group was 9.30%, which was lower than 25.58% in the control group, and the difference was statistically significant (P<0.05). Conclusion The efficacy of febuxostat combined with metformin in patients with T2DM com⁃bined with HUA is remarkable, which can reduce the uric acid and blood glucose levels of patients and reduce the oc⁃currence of adverse reactions.[Key words] Febuxostat; Metformin; Type 2 diabetes mellitus; Hyperuricemia; Uric acid; Blood glucose2型糖尿病（type 2 diabetes mellitus, T2DM）是指由于遗传、环境等因素导致糖代谢紊乱使机体持续[作者简介]张艺羡（1988-），女，本科，主管药师，研究方向为药师调剂。
德谷门冬双胰岛素注射液治疗2_型糖尿病的疗效及安全性研究
DOI：10.16658/ki.1672-4062.2023.19.084德谷门冬双胰岛素注射液治疗2型糖尿病的疗效及安全性研究戴卉，张开凤，朱凤丽江苏省镇江市丹徒区人民医院内分泌科，江苏镇江212000[摘要]目的探讨德谷门冬双胰岛素注射液在2型糖尿病中的效果以及安全性。
方法选取2022年1月—2023年7月江苏省镇江市丹徒区人民医院收治的62例2型糖尿病患者为研究对象，按随机数表法分为对照组（n=31）和观察组（n=31）。
对照组患者接受门冬胰岛素30注射液治疗，观察组患者接受德谷门冬双胰岛素注射治疗。
对比两组患者临床疗效、血糖变化和不良反应发生率。
结果观察组治疗有效为96.77%，高于对照组的77.42%，差异有统计学意义（χ2=5.167，P=0.023）。
治疗前，两组患者血糖水平比较，差异无统计学意义（P>0.05）；治疗后，两组患者血糖水平均改善，且观察组血糖指标低于对照组，差异有统计学意义（P< 0.05）。
观察组不良反应发生率低与对照组，差异有统计学意义（P<0.05）。
结论德谷门冬双胰岛素的应用可以明显改善2型糖尿病患者血糖水平，疗效更为确切，且安全性更高，不会增加用药后不良反应。
[关键词] 2型糖尿病；德谷门冬双胰岛素；门冬胰岛素30注射液；安全性[中图分类号] R587 [文献标识码] A [文章编号] 1672-4062（2023）10（a）-0084-04Study on the Efficacy and Safety of Insulin Degludec and Insulin Aspart Injection in the Treatment of Type 2 Diabetes MellitusDAI Hui, ZHANG Kaifeng, ZHU FengliDepartment of Endocrinology, Zhenjiang Dantu District People's Hospital, Zhenjiang, Jiangsu Province, 212000 China [Abstract] Objective To explore the effect and safety of insulin degludec and insulin aspart injection in type 2 diabe⁃tes mellitus.Methods 62 patients of type 2 diabetes mellitus patients admitted to Zhenjiang Dantu District People's Hospital, Jiangsu Province from January 2022 to July 2023 were selected as study objects and divided into the control group (n=31) and the observation group (n=31) by taking the random number table method. The patients in the control group were treated with insulin aspart 30 injection and the patients in the observation group were treated with insulin degludec and insulin aspart injection. Compared the clinical efficacy, the changes in blood glucose and the incidence of adverse reactions between the two groups of patients.Results The treatment effectiveness of the observation group was 96.77%, which was higher than that of the control group, which was 77.42%, and the difference was statistically significant (χ2=5.167, P=0.023). There was no statistically significant difference in blood glucose levels between the two groups before treatment (P>0.05). After treatment, blood glucose levels improved in both groups, and the level of blood glucose in the observation group were lower than those in the control group, and the difference was statistically significant (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (P<0.05).Conclusion The application of insulin degludec and in⁃sulin aspart can significantly improve the blood glucose level of patients with type 2 diabetes mellitus, the efficacy is more accurate, and the safety is higher, and it will not increase the occurrence of adverse reactions after the use of medication.[作者简介]戴卉（1985-），女，本科，主治医师，研究方向为内分泌科。
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Product Name:
PP1CAS No.:
172889-26-8
Product Data Sheet
Cat. No.:
HY-13804MWt:
281.36Formula:
C16H19N5Purity :
>98%
Solubility:Mechanisms:Biological Activity:
Pathways:Protein Tyrosine Kinase/RTK; Target:Src
Pathways:Protein Tyrosine Kinase/RTK; Target:PDGFR 25°C: DMSO
g y Description:
IC50 Value: 0.2 uM (recombinant p60c-src); 0.1 uM (PDGF b-receptor in Swiss 3T3 cell) [1]
PP1(AGL1872) is a Src family kinase,inhibitor. PP1/AGL1872 potently inhibited recombinant p60c-src in vitro and Src-dependent tyrosine phosphorylation in p60c-srcF572-transformed NIH3T3 cells.PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs.
in vitro: PP1/AGL1872 inhibits p60c-src in vitro with an IC50 of 0.2 mmol/L; ie, we found an IC50 '50times higher than that reported for inhibition of p56Lck in vitro.27 PP2/AGL1879 had a somewhat lower activity in this assay with an IC50 of 0.3 mmol/L [1]. PP1/AGL1872 potently inhibit PDGF b-References:
[1]. Waltenberger J, et al. A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling. Circ Res. 1999 Jul 9;85(1):12-22.y y []p y
receptor autokinase activity in Swiss 3T3 cell membranes (IC50 0.1 mmol/L), in preparations of partially purified human PDGF b-receptor (IC50 0.1 mmol/L) and in intact Swiss 3T3 cells (IC50 0.5mmol/L)PP1/AGL1872
()
[2]. Cardenas M, et al. Selective protein kinase inhibitors block head-specific differentiation in hydra.Cell Signal. 2000 Oct;12(9-10):649-58.
Caution: Not fully tested. For research purposes only
Medchemexpress LLC
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