Euthyphro Review
m6a甲基转移酶METTL3调控KAI1
细胞与分子生物学m6a甲基转移酶METTL3调控KAI1/CD82表达介导垂体神经内分泌肿瘤细胞生物学行为的机制研究郑锴1，罗秀玲2，张玮豪1，刘宇利1，李玉明1，廖尚高3摘要：目的研究m6a甲基转移酶METTL3调控KAI1/CD82表达介导垂体神经内分泌肿瘤细胞增殖、迁移与侵袭的机制。
方法通过实时荧光聚合酶链反应（qPCR）和蛋白免疫印迹测定大鼠垂体细胞、大鼠垂体神经内分泌肿瘤细胞系GH3和MMQ中的METTL3与KAI1/CD82表达水平。
体外培养GH3细胞，将其随机分为对照组、METTL3过表达质粒组、METTL3空质粒组、METTL3siRNA组、METTL3siRNA阴性对照组，经分组转染后，通过qPCR和蛋白免疫印迹检测各组细胞METTL3与KAI1/CD82表达；通过CCK-8实验检测各组细胞活力；通过细胞划痕、Transwell侵袭实验检测各组细胞迁移侵袭情况；通过甲基化RNA免疫共沉淀（MeRIP）实验检测各组细胞KAI1/CD82m6A甲基化修饰情况。
结果相比大鼠垂体细胞，大鼠垂体神经内分泌肿瘤细胞系GH3及MMQ中的METTL3蛋白及mRNA表达水平明显升高，KAI1/CD82蛋白及mRNA表达水平明显降低（P＜0.05）。
与对照组相比，METTL3空质粒组、METTL3siRNA阴性对照组细胞各指标差异无统计学意义；与对照组、METTL3空质粒组相比，METTL3过表达质粒组细胞活力、迁移距离、侵袭细胞数、METTL3蛋白及mRNA表达水平、KAI1/CD82m6A甲基化水平升高（P＜0.05），KAI1/CD82蛋白及mRNA表达水平降低（P＜0.05）；与对照组、METTL3siRNA阴性对照组相比，METTL3siRNA组细胞活力、迁移距离、侵袭细胞数、METTL3蛋白及mRNA表达水平、KAI1/CD82m6A甲基化水平降低（P＜0.05），KAI1/ CD82蛋白及mRNA表达水平升高（P＜0.05）。
210996952_伏诺拉生治疗胃食管反流有效性和安全性的Meta分析
robust and the possibility of publication bias was small.
CONCLUSIONS Vonoprazan has a considerable effectiveness
and safety in the treatment of gastroesophageal reflux disease.
of treatment （P＜0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were
Δ 基金项目 四川省区域创新合作项目（No.2020YFQ0010）
Mei，ZHENG
Minglin，FAN
Ping（Dept. of
Pharmacy，West China Hospital of Sichuan University，Chengdu 610041，China）
ABSTRACT
OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan in the treatment of gastroesophageal
愈率，不同洛杉矶分级治愈率；安全性指标包括：药物不
化系统疾病 。流行病学资料显示，GERD 患病率在全
良事件、腹泻、鼻咽炎、上呼吸道感染、碱性磷酸酶升高
球范围内呈上升趋势，西方国家为 10%～20%，我国为
发生率。
[1]
1.9%～7.0% 。GERD 的典型症状包括烧心（胃灼热）和
发酵法生产1,3-丙二醇的研究进展
2017年第36卷第4期 CHEMICAL INDUSTRY AND ENGINEERING PROGRESS·1395·化 工 进展发酵法生产1,3-丙二醇的研究进展李晓姝，张霖，高大成，师文静，樊亚超（中国石油化工股份有限公司抚顺石油化工研究院，辽宁 抚顺113001）摘要：1,3-丙二醇是一种重要的化合物，近年来由于其用途的不断拓宽而越来越受到广泛重视。
生物合成法生产1,3-丙二醇具有绿色高效、使用可再生能源等特点，是目前最具前景的生产方式。
本文从发酵菌种、发酵工艺、发酵过程优化和精制提纯几个方面对发酵法生产1,3-丙二醇的研究现状进行了介绍。
提出为使生物法生产1,3-丙二醇在成本上与化学法相比更具优势，在提高产量的同时应该引入新技术、新手段对发酵过程进行强化，使得过程更加精准且易于控制；同时指出综合考虑经济性与能耗问题，对发酵与分离的全过程进行整合，是今后发酵法生产1,3-丙二醇实现产业化的研究重点。
关键词：1,3-丙二醇；发酵；生物转化；甘油中图分类号：TQ 923 文献标志码：A 文章编号：1000–6613（2017）04–1395–09 DOI ：10.16085/j.issn.1000-6613.2017.04.032Progress on the production of 1,3-propanediol by fermentationLI Xiaoshu ，ZHANG Lin ，GAO Dacheng ，SHI Wenjing ，F AN Yachao（Fushun Research Institute of Petroleum and Petrochemicals ，SINOPEC ，Fushun 113001，Liaoning ，China ）Abstract ：1,3-propanediol is an important chemical compound ，which has recently received more andmore attention due to its wide applications. Synthesizing 1,3-propanediol via the biological method has some merits ，such as green ，high efficiency ，and sustainable. This method is the most promising for the 1,3-propanediol production.In this paper ，the research advances on production of 1,3-propanediol by fermentation were reviewed with regard to fermentative strains ，fermentation process ，process optimization and purification. To have a low cost advantage over the other chemical synthesizes ，the biological method needs to increase the concentration of 1,3-propanediol ，to strengthen the fermentation process that is more accurate and easier control. Economy and energy consumption need to be considered to integrate the whole process of fermentation and separation ，which should be the focus of research and industrial production of 1,3-propanediol by biological process in the future. Key words ：1,3-propanediol ；fermentation ；bioconversion ；glycerol1,3-丙二醇（1,3-PD ）是一种重要且用途广泛的化工原料，其与对苯二甲酸聚合合成的聚对苯二甲酸丙二醇酯（PTT ），是一种性质优良的聚酯材料。
稳定性英文版
HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFLUOXETINE HClC17H18F3NO•HClM.W. = 345.79CAS — 59333-67-4STABILITY INDICATINGA S S A Y V A L I D A T I O NMethod is suitable for:ýIn-process controlþProduct ReleaseþStability indicating analysis (Suitability - US/EU Product) CAUTIONFLUOXETINE HYDROCHLORIDE IS A HAZARDOUS CHEMICAL AND SHOULD BE HANDLED ONLY UNDER CONDITIONS SUITABLE FOR HAZARDOUS WORK.IT IS HIGHLY PRESSURE SENSITIVE AND ADEQUATE PRECAUTIONS SHOULD BE TAKEN TO AVOID ANY MECHANICAL FORCE (SUCH AS GRINDING, CRUSHING, ETC.) ON THE POWDER.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationTABLE OF CONTENTS INTRODUCTION........................................................................................................................ PRECISION............................................................................................................................... System Repeatability ................................................................................................................ Method Repeatability................................................................................................................. Intermediate Precision .............................................................................................................. LINEARITY................................................................................................................................ RANGE...................................................................................................................................... ACCURACY............................................................................................................................... Accuracy of Standard Injections................................................................................................ Accuracy of the Drug Product.................................................................................................... VALIDATION OF FLUOXETINE HCl AT LOW CONCENTRATION........................................... Linearity at Low Concentrations................................................................................................. Accuracy of Fluoxetine HCl at Low Concentration..................................................................... System Repeatability................................................................................................................. Quantitation Limit....................................................................................................................... Detection Limit........................................................................................................................... VALIDATION FOR META-FLUOXETINE HCl (POSSIBLE IMPURITIES).................................. Meta-Fluoxetine HCl linearity at 0.05% - 1.0%........................................................................... Detection Limit for Fluoxetine HCl.............................................................................................. Quantitation Limit for Meta Fluoxetine HCl................................................................................ Accuracy for Meta-Fluoxetine HCl ............................................................................................ Method Repeatability for Meta-Fluoxetine HCl........................................................................... Intermediate Precision for Meta-Fluoxetine HCl......................................................................... SPECIFICITY - STABILITY INDICATING EVALUATION OF THE METHOD............................. FORCED DEGRADATION OF FINISHED PRODUCT AND STANDARD..................................1. Unstressed analysis...............................................................................................................2. Acid Hydrolysis stressed analysis..........................................................................................3. Base hydrolysis stressed analysis.........................................................................................4. Oxidation stressed analysis...................................................................................................5. Sunlight stressed analysis.....................................................................................................6. Heat of solution stressed analysis.........................................................................................7. Heat of powder stressed analysis.......................................................................................... System Suitability stressed analysis.......................................................................................... Placebo...................................................................................................................................... STABILITY OF STANDARD AND SAMPLE SOLUTIONS......................................................... Standard Solution...................................................................................................................... Sample Solutions....................................................................................................................... ROBUSTNESS.......................................................................................................................... Extraction................................................................................................................................... Factorial Design......................................................................................................................... CONCLUSION...........................................................................................................................ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationBACKGROUNDTherapeutically, Fluoxetine hydrochloride is a classified as a selective serotonin-reuptake inhibitor. Effectively used for the treatment of various depressions. Fluoxetine hydrochloride has been shown to have comparable efficacy to tricyclic antidepressants but with fewer anticholinergic side effects. The patent expiry becomes effective in 2001 (US). INTRODUCTIONFluoxetine capsules were prepared in two dosage strengths: 10mg and 20mg dosage strengths with the same capsule weight. The formulas are essentially similar and geometrically equivalent with the same ingredients and proportions. Minor changes in non-active proportions account for the change in active ingredient amounts from the 10 and 20 mg strength.The following validation, for the method SI-IAG-206-02 , includes assay and determination of Meta-Fluoxetine by HPLC, is based on the analytical method validation SI-IAG-209-06. Currently the method is the in-house method performed for Stability Studies. The Validation was performed on the 20mg dosage samples, IAG-21-001 and IAG-21-002.In the forced degradation studies, the two placebo samples were also used. PRECISIONSYSTEM REPEATABILITYFive replicate injections of the standard solution at the concentration of 0.4242mg/mL as described in method SI-IAG-206-02 were made and the relative standard deviation (RSD) of the peak areas was calculated.SAMPLE PEAK AREA#15390#25406#35405#45405#55406Average5402.7SD 6.1% RSD0.1ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::PRECISION - Method RepeatabilityThe full HPLC method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method repeated six times and the relative standard deviation (RSD) was calculated.SAMPLENumber%ASSAYof labeled amountI 96.9II 97.8III 98.2IV 97.4V 97.7VI 98.5(%) Average97.7SD 0.6(%) RSD0.6PRECISION - Intermediate PrecisionThe full method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method was repeated six times by a second analyst on a different day using a different HPLC instrument. The average assay and the relative standard deviation (RSD) were calculated.SAMPLENumber% ASSAYof labeled amountI 98.3II 96.3III 94.6IV 96.3V 97.8VI 93.3Average (%)96.1SD 2.0RSD (%)2.1The difference between the average results of method repeatability and the intermediate precision is 1.7%.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationLINEARITYStandard solutions were prepared at 50% to 200% of the nominal concentration required by the assay procedure. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over the concentration range required. Y-Intercept was found to be insignificant.RANGEDifferent concentrations of the sample (IAG-21-001) for the 20mg dosage form were prepared, covering between 50% - 200% of the nominal weight of the sample.Conc. (%)Conc. (mg/mL)Peak Area% Assayof labeled amount500.20116235096.7700.27935334099.21000.39734463296.61500.64480757797.52000.79448939497.9(%) Average97.6SD 1.0(%) RSD 1.0ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::RANGE (cont.)The results demonstrate linearity as well over the specified range.Correlation coefficient (RSQ)0.99981 Slope11808.3Y -Interceptresponse at 100%* 100 (%) 0.3%ACCURACYACCURACY OF STANDARD INJECTIONSFive (5) replicate injections of the working standard solution at concentration of 0.4242mg/mL, as described in method SI-IAG-206-02 were made.INJECTIONNO.PEAK AREA%ACCURACYI 539299.7II 540599.9III 540499.9IV 5406100.0V 5407100.0Average 5402.899.9%SD 6.10.1RSD, (%)0.10.1The percent deviation from the true value wasdetermined from the linear regression lineHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::ACCURACY OF THE DRUG PRODUCTAdmixtures of non-actives (placebo, batch IAG-21-001 ) with Fluoxetine HCl were prepared at the same proportion as in a capsule (70%-180% of the nominal concentration).Three preparations were made for each concentration and the recovery was calculated.Conc.(%)Placebo Wt.(mg)Fluoxetine HCl Wt.(mg)Peak Area%Accuracy Average (%)70%7079.477.843465102.27079.687.873427100.77079.618.013465100.0101.0100%10079.6211.25476397.910080.8011.42491799.610079.6011.42485498.398.6130%13079.7214.90640599.413080.3114.75632899.213081.3314.766402100.399.618079.9920.10863699.318079.3820.45879499.418080.0820.32874899.599.4Placebo, Batch Lot IAG-21-001HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION OF FLUOXETINE HClAT LOW CONCENTRATIONLINEARITY AT LOW CONCENTRATIONSStandard solution of Fluoxetine were prepared at approximately 0.02%-1.0% of the working concentration required by the method SI-IAG-206-02. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over this range.ACCURACY OF FLUOXETINE HCl AT LOW CONCENTRATIONThe peak areas of the standard solution at the working concentration were measured and the percent deviation from the true value, as determined from the linear regression was calculated.SAMPLECONC.µg/100mLAREA FOUND%ACCURACYI 470.56258499.7II 470.56359098.1III 470.561585101.3IV 470.561940100.7V 470.56252599.8VI 470.56271599.5(%) AverageSlope = 132.7395299.9SD Y-Intercept = -65.872371.1(%) RSD1.1HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSystem RepeatabilitySix replicate injections of standard solution at 0.02% and 0.05% of working concentration as described in method SI-IAG-206-02 were made and the relative standard deviation was calculated.SAMPLE FLUOXETINE HCl AREA0.02%0.05%I10173623II11503731III10103475IV10623390V10393315VI10953235Average10623462RSD, (%) 5.0 5.4Quantitation Limit - QLThe quantitation limit ( QL) was established by determining the minimum level at which the analyte was quantified. The quantitation limit for Fluoxetine HCl is 0.02% of the working standard concentration with resulting RSD (for six injections) of 5.0%. Detection Limit - DLThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected. The detection limit of Fluoxetine HCl is about 0.01% of the working standard concentration.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION FOR META-FLUOXETINE HCl(EVALUATING POSSIBLE IMPURITIES)Meta-Fluoxetine HCl linearity at 0.05% - 1.0%Relative Response Factor (F)Relative response factor for Meta-Fluoxetine HCl was determined as slope of Fluoxetine HCl divided by the slope of Meta-Fluoxetine HCl from the linearity graphs (analysed at the same time).F =132.7395274.859534= 1.8Detection Limit (DL) for Fluoxetine HClThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected.Detection limit for Meta Fluoxetine HCl is about 0.02%.Quantitation Limit (QL) for Meta-Fluoxetine HClThe QL is determined by the analysis of samples with known concentration of Meta-Fluoxetine HCl and by establishing the minimum level at which the Meta-Fluoxetine HCl can be quantified with acceptable accuracy and precision.Six individual preparations of standard and placebo spiked with Meta-Fluoxetine HCl solution to give solution with 0.05% of Meta Fluoxetine HCl, were injected into the HPLC and the recovery was calculated.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES].Approx.Conc.(%)Known Conc.(µg/100ml)Area in SpikedSampleFound Conc.(µg/100mL)Recovery (%)0.0521.783326125.735118.10.0521.783326825.821118.50.0521.783292021.55799.00.0521.783324125.490117.00.0521.783287220.96996.30.0521.783328526.030119.5(%) AVERAGE111.4SD The recovery result of 6 samples is between 80%-120%.10.7(%) RSDQL for Meta Fluoxetine HCl is 0.05%.9.6Accuracy for Meta Fluoxetine HClDetermination of Accuracy for Meta-Fluoxetine HCl impurity was assessed using triplicate samples (of the drug product) spiked with known quantities of Meta Fluoxetine HCl impurity at three concentrations levels (namely 80%, 100% and 120% of the specified limit - 0.05%).The results are within specifications:For 0.4% and 0.5% recovery of 85% -115%For 0.6% recovery of 90%-110%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES]Approx.Conc.(%)Known Conc.(µg/100mL)Area in spikedSample Found Conc.(µg/100mL)Recovery (%)[0.4%]0.4174.2614283182.66104.820.4174.2614606187.11107.370.4174.2614351183.59105.36[0.5%]0.5217.8317344224.85103.220.5217.8316713216.1599.230.5217.8317341224.81103.20[0.6%]0.6261.3918367238.9591.420.6261.3920606269.81103.220.6261.3920237264.73101.28RECOVERY DATA DETERMINED IN SPIKED SAMPLESHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::REPEATABILITYMethod Repeatability - Meta Fluoxetine HClThe full method (as described in SI-IAG-206-02) was carried out on the finished drug product representing lot number IAG-21-001-(1). The HPLC method repeated serially, six times and the relative standard deviation (RSD) was calculated.IAG-21-001 20mg CAPSULES - FLUOXETINESample% Meta Fluoxetine % Meta-Fluoxetine 1 in Spiked Solution10.0260.09520.0270.08630.0320.07740.0300.07450.0240.09060.0280.063AVERAGE (%)0.0280.081SD 0.0030.012RSD, (%)10.314.51NOTE :All results are less than QL (0.05%) therefore spiked samples with 0.05% Meta Fluoxetine HCl were injected.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::Intermediate Precision - Meta-Fluoxetine HClThe full method as described in SI-IAG-206-02 was applied on the finished product IAG-21-001-(1) .It was repeated six times, with a different analyst on a different day using a different HPLC instrument.The difference between the average results obtained by the method repeatability and the intermediate precision was less than 30.0%, (11.4% for Meta-Fluoxetine HCl as is and 28.5% for spiked solution).IAG-21-001 20mg - CAPSULES FLUOXETINESample N o:Percentage Meta-fluoxetine% Meta-fluoxetine 1 in spiked solution10.0260.06920.0270.05730.0120.06140.0210.05850.0360.05560.0270.079(%) AVERAGE0.0250.063SD 0.0080.009(%) RSD31.514.51NOTE:All results obtained were well below the QL (0.05%) thus spiked samples slightly greater than 0.05% Meta-Fluoxetine HCl were injected. The RSD at the QL of the spiked solution was 14.5%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSPECIFICITY - STABILITY INDICATING EVALUATIONDemonstration of the Stability Indicating parameters of the HPLC assay method [SI-IAG-206-02] for Fluoxetine 10 & 20mg capsules, a suitable photo-diode array detector was incorporated utilizing a commercial chromatography software managing system2, and applied to analyze a range of stressed samples of the finished drug product.GLOSSARY of PEAK PURITY RESULT NOTATION (as reported2):Purity Angle-is a measure of spectral non-homogeneity across a peak, i.e. the weighed average of all spectral contrast angles calculated by comparing all spectra in the integrated peak against the peak apex spectrum.Purity Threshold-is the sum of noise angle3 and solvent angle4. It is the limit of detection of shape differences between two spectra.Match Angle-is a comparison of the spectrum at the peak apex against a library spectrum.Match Threshold-is the sum of the match noise angle3 and match solvent angle4.3Noise Angle-is a measure of spectral non-homogeneity caused by system noise.4Solvent Angle-is a measure of spectral non-homogeneity caused by solvent composition.OVERVIEWT he assay of the main peak in each stressed solution is calculated according to the assay method SI-IAG-206-02, against the Standard Solution, injected on the same day.I f the Purity Angle is smaller than the Purity Threshold and the Match Angle is smaller than the Match Threshold, no significant differences between spectra can be detected. As a result no spectroscopic evidence for co-elution is evident and the peak is considered to be pure.T he stressed condition study indicated that the Fluoxetine peak is free from any appreciable degradation interference under the stressed conditions tested. Observed degradation products peaks were well separated from the main peak.1® PDA-996 Waters™ ; 2[Millennium 2010]ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFORCED DEGRADATION OF FINISHED PRODUCT & STANDARD 1.UNSTRESSED SAMPLE1.1.Sample IAG-21-001 (2) (20mg/capsule) was prepared as stated in SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 98.5%.SAMPLE - UNSTRESSEDFluoxetine:Purity Angle:0.075Match Angle:0.407Purity Threshold:0.142Match Threshold:0.4251.2.Standard solution was prepared as stated in method SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 100.0%.Fluoxetine:Purity Angle:0.078Match Angle:0.379Purity Threshold:0.146Match Threshold:0.4272.ACID HYDROLYSIS2.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of conc. HCl was added to this solution The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system after filtration.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 98.8%.SAMPLE- ACID HYDROLYSISFluoxetine peak:Purity Angle:0.055Match Angle:0.143Purity Threshold:0.096Match Threshold:0.3712.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask. 20mL Diluent were added. 2mL of conc. HCl were added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 97.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSTANDARD - ACID HYDROLYSISFluoxetine peak:Purity Angle:0.060Match Angle:0.060Purity Threshold:0.099Match Threshold:0.3713.BASE HYDROLYSIS3.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weight into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 99.3%.SAMPLE - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.063Match Angle:0.065Purity Threshold:0.099Match Threshold:0.3623.2.Standard stock solution was prepared as per method SI-IAG-206-02 : About 22mg Fluoxetine HCl was weighed into a 50mL volumetric flask. 20mL Diluent was added. 2mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH=5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease - 99.5%.STANDARD - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.081Match Angle:0.096Purity Threshold:0.103Match Threshold:0.3634.OXIDATION4.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02. An equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent added and the solution sonicated for 10 minutes.1.0mL of 30% H2O2 was added to the solution and allowed to stand for 5 hours, then made up to volume with Diluent, filtered and injected into HPLC system.Fluoxetine peak intensity decreased to 95.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSAMPLE - OXIDATIONFluoxetine peak:Purity Angle:0.090Match Angle:0.400Purity Threshold:0.154Match Threshold:0.4294.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask and 25mL Diluent were added. 2mL of 30% H2O2 were added to this solution which was standing for 5 hours, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity decreased to 95.8%.STANDARD - OXIDATIONFluoxetine peak:Purity Angle:0.083Match Angle:0.416Purity Threshold:0.153Match Threshold:0.4295.SUNLIGHT5.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1hour. The BST was set to 35°C and the ACT was 45°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak decreased to 91.2% and the dark control solution showed assay of 97.0%. The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak was observed at RRT of 1.5 (2.7%).The total percent of Fluoxetine peak with the degradation peak is about 93.9%.SAMPLE - SUNLIGHTFluoxetine peak:Purity Angle:0.093Match Angle:0.583Purity Threshold:0.148Match Threshold:0.825 ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSUNLIGHT (Cont.)5.2.Working standard solution was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1.5 hour. The BST was set to 35°C and the ACT was 42°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak was decreased to 95.2% and the dark control solution showed assay of 99.5%.The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak were observed at RRT of 1.5 (2.3).The total percent of Fluoxetine peak with the degradation peak is about 97.5%. STANDARD - SUNLIGHTFluoxetine peak:Purity Angle:0.067Match Angle:0.389Purity Threshold:0.134Match Threshold:0.8196.HEAT OF SOLUTION6.1.Sample solution of IAG-21-001-(2) (20 mg/capsule) was prepared as in method SI-IAG-206-02 . Equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution was sonicated for 10 minutes and made up to volume with Diluent. 4mL solution was transferred into a suitable crucible, heated at 105°C in an oven for 2 hours. The sample was cooled to ambient temperature, filtered and injected into the HPLC system.Fluoxetine peak was decreased to 93.3%.SAMPLE - HEAT OF SOLUTION [105o C]Fluoxetine peak:Purity Angle:0.062Match Angle:0.460Purity Threshold:0.131Match Threshold:0.8186.2.Standard Working Solution (WS) was prepared under method SI-IAG-206-02 . 4mL of the working solution was transferred into a suitable crucible, placed in an oven at 105°C for 2 hours, cooled to ambient temperature and injected into the HPLC system.Fluoxetine peak intensity did not decrease - 100.5%.ED. N0: 04Effective Date:APPROVED::。
氯代多氟烷基醚磺酸盐环境污染及治理研究进展
生态毒理学报Asian Journal of Ecotoxicology第18卷第2期2023年4月V ol.18,No.2Apr.2023㊀㊀基金项目:国家自然科学基金资助项目(51608079);重庆市自然科学基金资助项目(cstc2020jcyj -msxmX0176);重庆市教育委员会科学技术研究项目(KJQN202000745);重庆市建设科技项目(20210709);重庆市研究生联合培养基地建设项目(JDLHPYJD2020024)㊀㊀第一作者:余薇薇(1985 ),女,博士,教授,研究方向为污染治理㊁水环境修复,E -mail:*****************.cn ㊀㊀*通信作者(Corresponding author ),E -mail:*****************.cnDOI:10.7524/AJE.1673-5897.20220708001余薇薇,韦采妮,毛羽丰,等.氯代多氟烷基醚磺酸盐环境污染及治理研究进展[J].生态毒理学报,2023,18(2):224-237Yu W W,Wei C N,Mao Y F,et al.Environmental pollution of chlorinated polyfluorinated ether sulfonates and treatment study:A critical review [J].Asi -an Journal of Ecotoxicology,2023,18(2):224-237(in Chinese)氯代多氟烷基醚磺酸盐环境污染及治理研究进展余薇薇1,*,韦采妮1,毛羽丰1,刘聪2,陈杰云3,赵雅倩4,疏明慧1,黎玥淇1,谭江琳11.重庆交通大学河海学院水利水运工程教育部重点实验室,重庆4000742.西南技术工程研究所,重庆4000393.重庆市渝北区建设管理事务中心,重庆4011204.重庆市黔江碧桂园房地产开发有限公司,重庆409000收稿日期:2022-07-08㊀㊀录用日期:2022-10-19摘要:氯代多氟烷基醚磺酸盐(chlorinated polyfluorinated ether sulfonates,Cl -PFESA)在中国作为全氟辛烷磺酸盐(perfluorooctane sulfonate,PFOS)替代物,被广泛应用于电镀工业中,Cl -PFESA 是目前最具生物持久性的全氟和多氟化合物(per -and polyfluoro -alkyl substances,PFASs),潜在毒性与PFOS 相当甚至高于许多传统PFASs ㊂其在各环境㊁动物及人体中已被频繁检出,是水环境㊁生物体甚至人体中PFASs 的主要贡献者㊂本文总结了Cl -PFESA 在各种环境介质㊁生物体及人体中的赋存情况,分析了吸附法㊁还原法㊁机械化学法和电化学法等处理技术对Cl -PFESA 的降解效果,并对Cl -PFESA 环境行为研究和人类健康风险评估提出展望,以期为Cl -PFESA 的生态风险评估和污染治理研究提供理论参考㊂关键词:氯代多氟烷基醚磺酸盐;污染现状;毒性;降解研究文章编号:1673-5897(2023)2-224-14㊀㊀中图分类号:X503㊀㊀文献标识码:AEnvironmental Pollution of Chlorinated Polyfluorinated Ether Sulfonates and Treatment Study :A Critical ReviewYu Weiwei 1,*,Wei Caini 1,Mao Yufeng 1,Liu Cong 2,Chen Jieyun 3,Zhao Yaqian 4,Shu Minghui 1,Li Yueqi 1,Tan Jianglin 11.Key Laboratory of Water Conservancy and Water Transport Engineering,Ministry of Education,Hohai College,Chongqing Jiaotong University,Chongqing 400074,China2.Southwest Technical Engineering Research Institute,Chongqing 400039,China3.Chongqing Yubei District Construction Management Affairs Center,Chongqing 401120,China4.Chongqing Qianjiang Bi Guiyuan Real Estate Development Corporation,Chongqing 409000,ChinaReceived 8July 2022㊀㊀accepted 19October 2022Abstract :Chlorinated polyfluorinated ether sulfonates (Cl -PFESA)is widely used in the electroplating industry as第2期余薇薇等:氯代多氟烷基醚磺酸盐环境污染及治理研究进展225㊀a perfluorooctane sulfonate(PFOS)alternative in China.However,Cl-PFESA is most the bio-persistent per-and polyfluoroalkyl substances(PFASs),with potential toxicity comparable to or even higher than many traditional PFASs.It has been frequently detected in various environments,animals and humans.It is a major contributor to PFASs in aquatic environments,organisms and even humans.This paper summarizes the occurrence of Cl-PFESA in various environmental media,organisms and human body.Meanwhile,the degradation effects of adsorption,re-duction,mechanochemistry and electrochemical treatment technologies on Cl-PFESA were analyzed.Moreover,the prospect of Cl-PFESA environmental behavior research and human health risk assessment are proposed.A theoreti-cal reference for ecological risk assessment and pollution control research of Cl-PFESA can be provided. Keywords:chlorinated polyfluorinated ether sulfonates;pollution status;toxicity;degradation studies㊀㊀全氟辛烷磺酸盐(perfluorooctane sulfonate, PFOS)作为典型的全氟和多氟化合物(per-and poly-fluoroalkylated substances,PFASs),具有许多独特的物理化学性质,包括疏水疏油㊁热稳定性㊁化学稳定性和表面活性,被广泛应用于工业和日常产品消费等领域[1]㊂同时PFOS表现出的高环境持久性㊁高生物积累性和长距离迁移特点,对环境和人类健康造成了威胁,2009年‘关于持久性有机污染物的斯德哥尔摩公约“(简称POPs公约)第4次缔约方大会上,PFOS被列入‘关于持久性有机污染物的斯德哥尔摩公约“附录B中[2],严格限制使用㊂我国在2013年8月批准了‘关于持久性有机污染物的斯德哥尔摩公约“新增列9种持久性有机污染物的‘关于附件A㊁附件B和附件C修正案“对PFOS及其盐类和全氟辛基磺酰氟做出限制规定㊂随着PFOS 的禁用,氯代多氟烷基醚磺酸盐(chlorinated polyflu-orinated ether sulfonates,Cl-PFESA)作为替代物在2009年的使用量达到20~30t[3],Cl-PFESA商品名为F-53B,在1970年开始广泛应用于中国电镀行业,2013年约有58%的镀铬厂使用Cl-PFESA抑制剂[4]㊂目前中国是唯一具有Cl-PFESA使用记录的国家,但缺乏对于Cl-PFESA的减量化和排放要求㊂2013年才首次报道了其环境浓度㊁持久性和毒性效应[5]㊂Cl-PFESA的环境持久性与PFOS相似,环境中的总停留时间估计为1038d[6]㊂最近的一项研究发现了Cl-PFESA的生物积累因子(bioaccumulation factors,BAFs)范围4.124~4.322高于PFOS(3.430~ 3.279)[7]㊂近年关于Cl-PFESA的环境影响已经引起关注,根据Web of Science的研究数据,采用VOS-viewer软件进行了以 Cl-PFESA 和 F-53B 为关键字的可视化分析如图1所示㊂目前的研究主要集中于环境介质中的检测㊁动物体和人体的暴露水平㊁对生物体的毒性效应,已有的综述主要关注于Cl-PFESA的对人体和生物体的毒性研究,对于其在环境中的检出和分布情况㊁对环境影响㊁去除研究等还未有系统的综述㊂因此本文根据相关文献报道,总结了Cl-PFESA目前在环境中的检出状况㊁动物和人体的暴露水平㊁对生物体潜在的毒性影响和去除研究进展,以期为进一步研究Cl-PFESA的环境行为,评估其生态风险提供一定参考依据㊂1㊀Cl-PFESA概述(Overview of Cl-PFESA) Cl-PFESA是作为灭铬雾剂被生产,在PFOS的碳链结构中引入醚键官能团,并用氯原子取代一个氟原子,可以降低成本和避免有毒化学品的使用[8]㊂Cl-PFESA依旧保持多氟化结构以及与PFOS相似的物理㊁化学特性,其log Kow值为7.07,具有较高的疏水性,C F是最强的化学键,因此Cl-PFESA具有较高的稳定性,高度耐氧化性能㊁耐酸耐碱㊁低溶解度,商业产品中主要形式是6:2Cl-PFESA,作为杂质产生的还有8:2Cl-PFESA[9]㊂Cl-PFESA分子式和化学结构式如表1所示㊂2㊀不同环境介质中Cl-PFESA的赋存情况(Occur-rence of Cl-PFESA in different environmental media)2.1㊀工业废水和市政污泥Cl-PFESA商业品作为烟雾抑制剂使用,可避免工人在电解过程中接触到空气中的Cr(Ⅵ)喷雾以起到保护作用,广泛应用于金属电镀行业,因此氟化工厂及相关电镀工业废水的排放是环境中Cl-PFESA 的重要来源[10]㊂据报道,某电镀工业废水中6:2Cl-PFESA和8:2Cl-PFESA含量分别为18%和0.7%,经污水处理工艺后收集的污泥样品中6:2Cl-PFESA 浓度达到22000ng㊃g-1,8:2Cl-PFESA浓度3200 ng㊃g-1[11]㊂在温州一个电镀工业的废水处理厂的进㊁出水口及受纳地表水中6:2Cl-PFESA检测浓度226㊀生态毒理学报第18卷达到μg ㊃L -1水平[5]㊂城市污水处理厂是各种全氟化合物的主要汇集地,也成为环境中污染物的重要次级点源㊂Ruan 等[12]在中国20个省市共56个污水处理厂脱水过程的新鲜消化污泥中均检测到6:2Cl -PFESA(0.02~209ng ㊃g -1,以干质量计)和8:2Cl -PFESA(0~31.8ng ㊃g -1,以干质量计)㊂在辽宁省一造纸厂废水排污口也检测到相关浓度282ng ㊃L -1,此外在未经处理的市政废水排放口中Cl -PFESA浓图1㊀关于关键词 Cl-PFESA 和 F-53B 的共现网络分析图注:圆圈大小表示关键词出现次数,颜色变化表示不同时间阶段的研究关注点㊂Fig.1㊀Co -occurrence network analysis of the keyword Cl -PFESA and F -53BNote:The size of the circle indicates the number of times the keyword appears,the color change indicates the research focus at different time periods.表1㊀Cl-PFESA 分子式㊁CAS 号及化学结构式Table 1㊀Molecular formula,CAS number and chemical structure of Cl -PFESA商品名Product name中文名Chinese name 英文缩写English abbreviations分子式Molecular formula化学结构式Chemical structureF -53B6:2氯代氟烷基醚磺酸盐6:2chlorinated polyfluorinatedether sulfonates6:2Cl -PFESAC 8F 16ClSO -48:2氯代氟烷基醚磺酸盐8:2chlorinated polyfluorinatedether sulfonates8:2Cl -PFESAC 10F 20ClSO -4第2期余薇薇等:氯代多氟烷基醚磺酸盐环境污染及治理研究进展227㊀度则达到了7600ng㊃L-1[13]㊂表明无论是工业废水或是市政污水处理厂均不能有效降解Cl-PFESA,相关的工业废水㊁污水排放以及污泥的综合使用不可避免地将残留Cl-PFESA排放入自然水体和土壤环境中,工业废水和市政污水是环境中Cl-PFESA的一个重要排放源㊂2.2㊀地表水和地下水表2列出了中国和其他国家部分河流中Cl-PFESA检出浓度㊂由于Cl-PFESA在中国被广泛使用,在中国水环境中的检出浓度高于其他国家,水生环境中的浓度与PFOS相当[14-15],且已成为中国水域中发现的主要PFASs之一[16]㊂中国排放量较大的地区主要集中在华南㊁华东地区,中部和西部地区排放量较低,与中国镀铬企业的位置分布相关[4]㊂在中国河流中检测到Cl-PFESA,浓度范围最高达78.5ng㊃L-1,主要以6:2Cl-PFAES为主,总体范围为0.01~77ng㊃L-1[17]㊂东部沿海河口处检出频率51%,浓度范围0.56~78.5ng㊃L-1,北方烟台沿海水表2㊀水体中Cl-PFESA的检测浓度Table2㊀Detection concentration of Cl-PFESA in water水体Water body检测浓度/(ng㊃L-1)Detection concentration/(ng㊃L-1)平均浓度/(ng㊃L-1)Average concentration/(ng㊃L-1)参考文献References渤海湾Bohai Bay0.43大沽河Dagu River50.60海河Haihe River36.80北塘河Beitang River19.40辽河Liao River 18.10[13]小清河Xiaoqing River0.419汤逊湖Lake Tangxun 0.149[22]南黄海South Yellow Sea0.080[23]南海沿海South China Sea Coast0.035[24]沱江Tuojiang River0.051~2.4800.392[25]黄河Yellow River0.01~0.290.140泰晤士河Thames River0.01~0.080.05特拉华河Delaware River0~0.080.02莱茵河Rhine River0.02~0.380.08梅拉伦湖Mälaren Lake 0~0.050.02[26]注: 为无可用数据㊂Note: no data available.228㊀生态毒理学报第18卷域浓度范围为2.86~44.4ng㊃L-1[18]㊂并且中国大陆湿降水中也检测到平均浓度为0.23ng㊃L-1的6:2 Cl-PFESA[19]㊂Wei等[20]发现江苏非工业地区地下水受到一定Cl-PFESA污染,6:2Cl-PFESA检测浓度0.17~1.83ng㊃L-1,检测浓度低于地表水,可能是Cl-PFESA的疏水性使其更容易滞留在土壤介质中,向下迁移和淋溶作用的浓度较低㊂值得关注的是,南极州东部一些融冰湖中同样检测到6:2Cl-PFE-SA,在除了部分地区的人类活动局部排放的PFASs,可能来自相关产品的释放,更多的主要来自空气传播[21]㊂因此大气沉降对非工业地区地下水中Cl-PFESA污染有重要影响㊂由于不同国家对于传统长链PFASs的使用替代物类型不同,Cl-PFESA 目前在中国环境中的检出率较高,特别是中国南部㊁中部沿海地区以及北方沿海地区,已成为水环境中的主要全氟污染物㊂在非工业地区地下水中也发现一定Cl-PFESA的污染,因此了解Cl-PFESA在环境介质中的迁移规律,对系统掌握Cl-PFESA对环境的影响有较大意义㊂2.3㊀土壤与大气Cl-PFESA在相关工业产品的生产制作以及使用过程,可通过粉末灰尘等途径进入到空气环境中,经大气介质进行远距离迁移,最终经过干湿沉降进入地表环境㊂在中国北方农田基质中发现6:2Cl-PFESA的检出频率(98%)高于PFOS(83%)[27]㊂在我国31个省住宅区土壤中Cl-PFESA具有98.9%检测率,其中6:2Cl-PFESA的浓度(0.16ʃ0.20)ng㊃g-1㊁8: 2Cl-PFESA浓度(0.61ʃ0.19)ng㊃g-1[28]㊂Cl-PFESA 具有较强的疏水性,土壤的吸附作用对Cl-PFESA 在地下的运输过程有较大影响,除了疏水作用㊁静电吸附,Cl-PFESA还可能通过配体交换取代羟基来与土壤矿物表面的金属氧化物相互作用,而土壤中Cu (Ⅱ)㊁Cr(Ⅵ)和硫酸盐对氧化物上吸附位点的竞争性占领,导致Cl-PFESA的吸附能力降低,因此一定浓度的Cu(Ⅱ)㊁Cr(Ⅵ)和硫酸盐可以促进Cl-PFESA在土壤环境中的迁移[29]㊂据报道,大连市大气颗粒物中检测到6:2Cl-PFESA浓度呈上升趋势,在2014年浓度达到722pg㊃m-3[30]㊂在河北石家庄室内灰尘中6:2Cl-PFESA平均浓度3.28ng㊃g-1,次于全氟丁酸(perfluorobutanoic acid,PFBA)和全氟辛酸(perfluo-rooctanoic acid,PFOA)[31],广州室内灰尘中检测到浓度为1.1ng㊃g-1[32]㊂Zhang等[33]采集的广州市一工业园区和某高校学生宿舍㊁清远市某电子垃圾拆卸区3个区域灰尘,均检测到一定浓度的6:2Cl-PFESA(平均检测浓度5.24㊁7.41和4.28ng㊃g-1)㊁8:2 Cl-PFESA(平均检测浓度2.88㊁1.24和1.72ng㊃g-1)㊂大气颗粒的沉降和含Cl-PFESA产品的直接释放是土壤环境中Cl-PFESA的重要来源,土壤的吸附作用会影响Cl-PFESA在地下环境的迁移,而土壤对Cl-PFESA的富集能力与土壤的理化性质㊁有机质含量有关,因此有必要关注Cl-PFESA在土壤中行为机制㊂此外,大气中Cl-PFESA的污染增加了人体呼吸暴露的危险,因此对于大气中Cl-PFESA的检测和防治十分重要㊂3㊀生物㊁人体暴露水平及毒性评估(Biological,hu-man exposure level and toxicity assessment) 3.1㊀生物暴露水平及毒性3.1.1㊀生物体暴露水平据报道Cl-PFESA在中国渤海海洋生物中广泛存在,浓度和检出频率也呈逐年上升趋势[34]㊂渤海生物体中6:2Cl-PFESA和8:2Cl-PFESA的检出频率分别为81.3%和2.67%,6:2Cl-PFESA在海洋生物中的检出频率甚至高于PFOS(77.33%),也有迹象表明Cl-PFESA可以在水生食物网中被生物放大[35]㊂6:2Cl-PFESA在野生鲫鱼中log BAFs范围为4.1~4.3[21],淡水藻中log BAFs为4.66ʃ0.06[36],在黑斑蛙中发现6:2Cl-PFESA的BAFs高于PFOS,且很容易在鱼组织中积累,消除缓慢[37-38]㊂有研究表明环境中聚苯乙烯微塑料的吸附作用可减少Cl-PFESA生物积累,但会诱导斑马鱼幼虫的炎症应激[39]㊂Cui等[40]首次报道的灵长类动物上海野生动物园的金丝猴体内6:2Cl-PFESA浓度会随着年龄的增长而显著增加,可能是6:2Cl-PFESA具有较大的生物持久性,同时环境介质中Cl-PFESA的暴露和日常饮食的摄入导致6:2Cl-PFESA浓度在体内不断积累㊂在格陵兰东部的北极野生动物㊁海洋哺乳动物中检测到生物积累,首次证实了其长期远程极地环境的范围传输潜力[41]㊂表3列出了6:2Cl-PFESA在动物组织中检测浓度㊂在不同生物体内积累差距可能归因于污染物暴露水平,生物的营养水平等,营养水平较高的生物体内Cl-PFESA检测出浓度高[42]㊂这些结果表明Cl-PFESA的生物积累性与PFOS相当甚至更高,在生物体的生物量积累特征值得持续关注㊂第2期余薇薇等:氯代多氟烷基醚磺酸盐环境污染及治理研究进展229㊀表3㊀动物体内6ʒ2Cl-PFESA检测浓度Table3㊀Detection concentration of6:2Cl-PFESA in animals动物Animal 组织Tissue地区Area检测浓度Detection concentration平均浓度Average concentration参考文献References鲫鱼Crucian carp 血液Blood中国小清河Xiaoqing River,China41.9ng㊃g-1中国汤逊湖Lake Tangxun,China20.9ng㊃g-1[22]西伯利亚虎Siberian tiger 血液Blood中国黑龙江Heilongjiang,China 0.078ng㊃mL-1[35]金丝猴Golden monkey 血液Blood黑叶猴Black langur 血液Blood中国铜陵Tongling,China0.01~0.04ng㊃mL-10.03ng㊃mL-1中国神农架自然保护区Shennongjia Nature Reserve,China0~0.02ng㊃mL-10.01ng㊃mL-1中国上海野生动物园Shanghai Wildlife Park,China0.03~0.11ng㊃mL-10.06ng㊃mL-1中国梧州育种中心Wuzhou breeding center,China0~0.13ng㊃mL-10.02ng㊃mL-1[40]黑斑蛙Black-spotted frog 心脏Heart肝脏Liver中国浙江Zhejiang,China105.3ng㊃g-1100.2ng㊃g-1[10]江豚Finless porpoise海鸥Seagull脉纹海螺Veined conch中国虾Chinese shrimp中国渤海Bohai Sea,China(2.84ʃ0.271)ng㊃g-1(以湿质量计Based on wet weight)(0.725ʃ0.092)ng㊃g-1(以湿质量计Based on wet weight)(0.351ʃ0.261)ng㊃g-1(以湿质量计Based on wet weight)(0.099ʃ0.063)ng㊃g-1(以湿质量计Based on wet weight)[35]北极熊Polar bear 肝脏Liver环斑海豹Ringed seal 肝脏Liver虎鲸Killer whale 肝脏Liver格陵兰海洋Greenland ocean(0.27ʃ0.04)ng㊃g-1(0.045ʃ0.004)ng㊃g-1(0.023ʃ0.009)ng㊃g-1[41]水濑Minase 英国东英吉利亚East Anglia,UK3.3ng㊃g-1(以湿质量计Based on wet weight)[43]江豚Finless porpoise 肝脏Liver中国南海South China Sea482ng㊃g-1(以干质量计Based on dry weight)座头鲸Humpback whales 肝脏Liver印度洋-太平洋Indo-Pacific973ng㊃g-1(以干质量计Based on dry weight)[44]注: 为无可用数据㊂Note: no data available.230㊀生态毒理学报第18卷3.1.2㊀Cl-PFESA的生物健康效应Cl-PFESA具有较高的生物毒性,认为Cl-PFE-SA的存在潜在健康风险㊂鱼类作为水生环境中的一类脊椎动物已被广泛作毒理学研究的模型㊂Cl-PFESA在斑马鱼胚胎中表现出了高于PFOS的生物浓缩潜力和最强的代谢干扰作用[45]㊂Wang等[5]发现Cl-PFESA和PFOS二者对斑马鱼致死浓度分别为15.5ng㊃L-1和17.0ng㊃L-1㊂将斑马鱼胚胎持续暴露3mg㊃L-1浓度时,Cl-PFESA在斑马鱼胚胎中高度积累,出现了孵化延迟㊁畸形发生率增加和存活率降低,产生心血管系统毒性[46]㊂斑马鱼胚胎在暴露于200μg㊃L-1浓度后,抗氧化基因的活性水平㊁mRNA和蛋白质水平均出现不同程度的下降,触发斑马鱼幼虫的氧化应激[47]㊂Cl-PFESA能够与斑马鱼甲状腺素运载蛋白结合,从而干扰甲状腺激素稳态[48]㊂一定浓度的Cl-PFESA可以使斑马鱼甲状腺素水平升高,破坏甲状腺内分泌系统[49],并且还具有跨代甲状腺干扰能力[50],对中国珍稀鲦鱼也具有相似的甲状腺破坏和跨代影响作用[51]㊂一定浓度Cl-PFESA暴露导致SD小鼠甲状腺激素的血清浓度降低,还诱导滤泡增生,破坏甲状腺功能[52]㊂Pan等[53]指出一定浓度的6:2Cl-PFESA可诱导雌性小鼠损伤和功能障碍㊂Zhang等[48]研究了6:2Cl-PFESA对成年小鼠的亚慢性肝毒性,暴露于剂量高于0.2mg㊃kg-1㊃d-1时相对肝脏质量增加,同时观察到肝脏细胞凋亡和增殖,表现出比PFOS更严重的肝毒性㊂将雌㊁雄性小鼠暴露于10mg㊃L-1的Cl-PFESA,10周后Cl-PFESA在结肠㊁回肠和血清中显著积累,并导致雌性和雄性小鼠的肠道屏障功能障碍和结肠炎症[54]㊂以上结果表明,Cl-PFESA毒性作用与PFOS 相当,甚至更高,在动物体中不断积累会产生胚胎和肝脏发育毒性㊁破坏甲状腺分泌系统和肠道功能㊂3.1.3㊀Cl-PFESA的生态毒性Cl-PFESA浓度达到mg级时,可干扰藻类叶绿素含量和细胞膜通透性,引起线粒体功能异常,对藻类的生长产生不良影响[35]㊂Pan等[55]报道了6:2Cl-PFAES可刺激绿豆根部产生过量的羟基自由基从而抑制绿豆的发育,对绿豆的植物毒性高于PFOS 可能是6:2Cl-PFAES对载体蛋白具有更高的亲和力㊂研究表明Cl-PFAES对藻类和植物的生长也产生抑制作用,当前环境中的污染浓度暂未对植物产生明显的毒性作用,但在植物中Cl-PFAES的富集有助于其在各食物链中放大㊂3.2㊀人体暴露水平及毒性3.2.1㊀人体暴露水平人体中Cl-PFESA的可通过呼吸㊁皮肤接触㊁饮用水和日常饮食摄入等途径积累,Cl-PFESA在中国人体样本的生物监测中也具有较高的出现率㊂在电镀厂工人以及高食用鱼类产品人群的血清中Cl-PFESA浓度为51.5ng㊃L-1和93.7ng㊃L-1,明显高于普通地区(4.78ng㊃L-1)[56]㊂有报道北京采集居民日常食用鱼类和肉质品中均含有一定浓度6:2Cl-PFESA,并且在鱼类样本中6:2Cl-PFESA的浓度水平远高于PFOA[57]㊂中国中部和东部地区普通居民血清中检测到6:2Cl-PFESA中值浓度2.18ng㊃mL-1,是第三高贡献的PFASs,积累浓度与年龄呈正相关性[58]㊂在山东省某氟化工厂附近2所学校学生血液中检测到6:2Cl-PFESA均值浓度分别为1.26 ng㊃mL-1和1.14ng㊃mL-1[59],6:2Cl-PFESA与人类血清蛋白的结合亲和力高于PFOS具有更高的生物积累潜力[60]㊂研究表明6:2Cl-PFESA已成为中国母体和脐带血清中第三大流行的PFASs㊂广州地区母亲血清中PFASs以PFOS(7.15ng㊃mL-1)为主,其次为6:2Cl-PFESA(2.41ng㊃mL-1)[61]㊂天津地区孕妇血清中6:2Cl-PFESA的暴露水平高于PFOS,平均浓度为6.436ng㊃mL-1[62]㊂Cl-PFESA在人类母乳中同样被广泛检测出,杭州女性母乳中6:2Cl-PFESA 含量0.028ng㊃mL-1,远低于血液中浓度[63]㊂但Cl-PFESA可能比传统的PFAS更容易穿过胎盘,而8:2 Cl-PFESA在胎盘上的运输程度高于6:2Cl-PFESA,可能是因为它具有较高的疏水性和较低的血浆蛋白结合亲和力[64]㊂母体体内积累的Cl-PFESA可以通过脐带和胎盘以及母乳喂养等途径转移至新生儿体内[65]㊂一项调查显示,在武汉新生儿样本中6:2Cl-PFESA和8:2Cl-PFESA的检出频率分别为100%和96%[66]㊂在人体中血液已广泛检测出Cl-PFE-SA,其检出浓度与生活环境和饮食习惯相关㊂母乳中也检测出一定浓度的Cl-PFESA,并发现Cl-PFE-SA可以通过脐带㊁胎盘和母乳等途径导致新生儿暴露的风险,因此Cl-PFESA在人体中的累积途径和规律,以及对新生儿健康的影响值得关注㊂3.2.2㊀Cl-PFESA对人体潜在影响Yang等[67]采用基于人类胚胎干细胞的心脏分化系统和全转录组学分析来评估Cl-PFESA和PFOS的潜在心脏发育毒性,发现Cl-PFESA抑制心脏分化并促进心外膜迁移的效果比PFOS更强,是第2期余薇薇等:氯代多氟烷基醚磺酸盐环境污染及治理研究进展231㊀因为Cl-PFESA暴露破坏了更多基因的表达并降低心脏分化效率㊂6:2Cl-PFESA可诱导人肝HL-7 702细胞系的细胞增殖,对细胞活力的毒性作用比PFOS更大,并且对人肝脂肪酸结合具有独特的结合模式与更高的结合能力[68]㊂人体暴露于低剂量的6:2Cl-PFAES后,可促进细胞脂质的积累,还可能加重肝脏代谢紊乱[69]㊂可见Cl-PFAES会对人体心脏㊁肝脏和细胞代谢产生影响,但对人体是否有其他危害还缺少调查,Cl-PFAES的毒性评估值得关注㊂4㊀对Cl-PFESA的去除研究(Study on removal of Cl-PFESA)㊀㊀自然环境Cl-PFESA的降解过程主要发生在水体,表层海洋,少部分会被沉积物掩埋和迁移至海洋[4],而6:2Cl-PFESA和8:2Cl-PFESA在土壤中的好氧生物降解可忽略不计[19]㊂现阶段工业废水对于Cl-PFESA处理多采用污泥沉淀法,但不同的处理单元对Cl-PFESA的处理效果影响较大,会出现Cl-PFESA的溶解态浓度富集,某电镀废水处理工艺出水中6:2Cl-PFESA平均浓度是进水浓度220ng㊃L-1的3.36倍[11]㊂有关Cl-PFESA降解方法主要有吸附法㊁还原法㊁机械化学法和电化学法㊂4.1㊀吸附法吸附法是常用且经济的方法,层状双金属氢氧化物材料(layered double hydroxide,LDH)对Cl-PFE-SA的吸附去除研究中,发现因为离子交换是主要机制,附加机制为O H/O/F和C F/Cl/H氢键,十二烷基硫酸钠(sodium dodecyl sulfate,SDS)具有更高的比表面积,较高的比表面积和SDS的存在可以分别产生更多的O H/O/F和C F/Cl/H氢键位点,进而增强SDS-LDH对Cl-PFESA的吸收㊂NO-3-LDH和SDS-LDH都能够从水体中快速去除Cl-PFESA,且SDS-LDH具有更高的去除效果[70]㊂有研究发现阴离子交换树脂IRA67对Cl-PFESA的吸附容量为4.2mmol㊃g-1,低pH条件下吸附效果较高,存在静电相互作用㊁疏水作用和胶束和半胶束形成等作用机制[71]㊂吸附法适用广泛,对污染物的去除具有较好的效果,吸附法仅从水环境中将污染物去除,但并未改变污染物的化学性质,无法使其矿化降解㊂4.2㊀还原法氰钴铵素(VB12)在催化还原降解卤代有机污染中具有广泛应用[72],可作为电子载体有效提高卤代有机污染物的降解速率和还原脱卤效果[73-74]㊂研究表明6:2Cl-PFESA对还原脱卤同样具有敏感性,在添加外源VB12的厌氧超还原试验中观察到定量的6:2Cl-PFESA发生快速转变,氢取代的多氟烷基醚磺酸盐(1H-6:2PFESA)确定为主要产物[75]㊂厌氧废水污泥㊁厌氧消化器中微生物和厌氧脱氯微生物可以不同程度下实现6:2Cl-PFESA完全脱氯,但未观察到还原性脱氟,6:2H-PFESA鉴定为唯一的代谢产物[76]㊂金属电镀设施附近2个不同区域的河水和沉积物样品中发现了氢取代的1H-6:2PFESA和1H-8:2PFESA,推测可能是生物降解产物㊂6:2Cl-PFESA在动物体由还原酶介导的生物转化产物为6:2H-PFESA[77]㊂因此氢取代的多氟烷基醚磺酸盐可能是Cl-PFESA降解的一条途径㊂高级还原法产生水合电子(e-aq)具有较高的还原点位(Eq=2.9V),e-aq可实现卤化有机污染物还原脱卤㊂氟原子的强电负性使其具有较强的电子亲和力,e-aq会优先攻氟原子实现还原脱氟,应用于PFASs的降解也是一种有效途径㊂Cao等[78]采用紫外光催化碘化钾产生的大量e-aq降解水溶液中Cl-PFESA,加入0.3mmol碘化钾,在反应45min内Cl-PFESA降解率超过95%㊂降解过程首先是脱氯,随后以醚键左侧的CF2基团为单元不断剥离,最后形成HOC2F4SO-3或HC2F4SO-3㊂UV/KI体系对Cl-PFESA具有较高的降解效果,但Cl-PFESA并没有被完全矿化,依旧存在中间产物和残留物,推测降解路径如图2所示㊂e-aq主导的还原降解对水体中的PFASs表现出有效的化学破坏,但降解过程会产生惰性的盐残留物(碘化物和硫酸盐),会增加出水中的总溶解固体含量,以及含氟副产物的鉴定和毒性需要考虑,并且水体中pH和溶解氧含量对还原降解效果具有较大的影响,要控制pH和溶解氧浓度会较大的增加处理成本[79]㊂4.3㊀机械化学法机械化学法通过机械力改变固体反应物的物理化学性质,可增强其反应活性,具有高效环保降解有机污染物的优势[80]㊂Yan等[81]采用机械化学法,使用过硫酸钠(sodium persulfate,PS)为研磨剂,加入碱活化剂时,在比例为PSʒNaOHʒCl-PFESA=4.17ʒ1.75ʒ0.05研磨8h后,88%的Cl-PFESA被破坏且实现较大矿化,氟化物回收率为54%,破坏效率也与研磨时间密切相关㊂通过球磨装置用氢氧化钾(KOH)研磨,Cl-PFESA被迅速破坏并高度矿化,有机232㊀生态毒理学报第18卷图2㊀UV /KI 降解Cl-PFESA 路径图[78]Fig.2㊀UV/KI degradation pathway of Cl -PFESA [78]C F 键断裂,生成甲酸盐和无机氟化物,最终产品为氟化钾(KF)㊁氯化钾(KCl)㊁过硫酸钾(K 2S 2O 8)和甲酸钾(HCOOK),降解路径如图3所示[82]㊂表明机械化学处理是一种有前途的Cl -PFESA 处理方法,可消除其持久性㊁生物累积性和毒性,但机械化学法仅适用于降解固体污染物,对于水环境中Cl -PFESA 的去除存在局限性㊂4.4㊀电化学法Zhuo 等[83]研究改性硼掺杂金刚石(boron -dopeddiamond,BDD)的4种阳极:BDD ㊁BDD/SnO 2㊁BDD/PbO 2和BDD/SnO 2-F 对Cl -PFESA 的电化学氧化降解中,BDD/PbO 2阳极在前10min 内对Cl -PFESA 去除率保持在较高水平,而BDD/SnO 2-F 具有更高的电催化能力,主要是阳极的析氧电位最高,F 的引入增加了氧化锡(SnO 2)的电导率,且F 的电负性较强,增加了阳极上的活性位点,使得更多的Cl -PFE -SA 能够吸附在阳极上直接发生电化学氧化,最大去除率达到95.6%㊂降解产物及其路径如图2~4所示㊂室内实验研究中,电化学法对污染物表现出较高的去除和矿化效果,今后方向应考虑对更优的阴/阳极材料的选择㊁对实际应用的适用性和经济问题㊂5㊀展望(Future )(1)Cl -PFESA 目前在中国环境中的检出率较高,水环境㊁沉积物㊁土壤㊁空气㊁动物甚至人体中被检测出,较高浓度检出主要集中在地表水以及沿海水域,已成为水环境甚至动物体中的主要全氟污染物,其在水体和动物体的含量分别在ng ㊃L -1和ng ㊃mL -1水平,其浓度仍不断积累和增加㊂但Cl -PFE -SA 在土壤和地下水中的污染数据缺乏,且在各介质中的迁移规律和环境归趋还未明确,因此系统探究Cl -PFESA 在环境的排放分布㊁迁移和转化规律对于评估其环境污染具有很大意义㊂(2)研究表明Cl -PFESA 表现出比PFOS 更严重的生物毒性,对水生鱼类具有肝毒性,影响胚胎发育,诱导性雌激素紊乱㊁甲状腺激素分泌紊乱并具有跨代干扰作用㊂对哺乳动物小鼠产生肝脏毒性㊁破坏甲状腺系统和肠道功能,对藻类和植物生长产生抑制作用㊂Cl -PFESA 在各环境介质中的污染浓度可能对动植物并未直接产生毒性作用,但在动植物体中的生物持久性和高积累性可以使其在各食物链中进行生物放大,累积到mg ㊃L -1水平时对动植物产生明显的毒性甚至致死作用㊂Cl -PFESA 在人体血液以及母乳中的检测含量达ng ㊃mL -1级别,可以通过胎盘㊁脐带和母乳传递而导致新生儿暴露的危险,目前的研究表明Cl -PFESA 对人类健康存在潜在危害,但相关数据还不足以对Cl -PFESA 进行系统的毒性评估,应对Cl -PFESA 在人体和动物各组织的分布㊁毒性作用机理和消除规律等进一步研究,以完善对Cl -PFESA 的风险评估㊂(3)Cl -PFESA 同样表现出难降解性㊁脱氟率低㊂污水处理工艺不能稳定有效降解Cl -PFESA ,由于其自身特殊化学结构使其对常规高级氧化降解具有一定抗性,而电化学氧化对Cl -PFESA 去除效果较好,但降解产物的鉴定㊁更多新材料和较优条件的选择还需更多的研究,对于实际大规模的应用也需考虑㊂VB 12等金属辅酶作为电子载体参与还原降解以及高级还原法对卤代有机污染物具有较好的还原脱卤效果,用于Cl -PFESA 的还原降解也可能是一种有效的降解方法,降解效果及其还原降解机制的进一步研究有利于环境Cl -PFESA 污染修复㊂机械化学法可实现固态Cl -PFESA 的去除和矿化,但对于水环境中Cl -PFESA 的去除具有局限性,吸附法目前是快速有效的水环境修复方法,但并没有改变污染。
右佐匹克隆片作用机理
右佐匹克隆片作用机理1. 引言右佐匹克隆片（Risperidone）是一种抗精神病药物，属于第二代抗精神病药物。
它主要用于治疗精神分裂症、双相情感障碍和自闭症等精神障碍。
本文将详细介绍右佐匹克隆片的作用机理，包括其药理学特点、受体亲和性以及对大脑功能的影响。
2. 药理学特点右佐匹克隆片是一种多巴胺D2受体拮抗剂，同时也具有5-羟色胺2A（5-HT2A）受体拮抗作用。
它通过调节多巴胺和5-羟色胺的水平来产生治疗效果。
2.1 多巴胺D2受体拮抗作用多巴胺是一种神经递质，与精神分裂症的发生密切相关。
在正常情况下，多巴胺通过与多巴胺D2受体结合，传递信号并调节神经活动。
而在精神分裂症患者中，多巴胺水平过高，导致神经传递过程异常增强。
右佐匹克隆片通过与多巴胺D2受体结合并拮抗其作用，降低多巴胺信号的传递效果。
这种拮抗作用可以减少多巴胺的过度活跃，从而改善精神分裂症的症状。
2.2 5-羟色胺2A受体拮抗作用5-羟色胺是另一种重要的神经递质，与情绪调节和认知功能密切相关。
在精神分裂症患者中，5-羟色胺水平也存在异常。
右佐匹克隆片具有5-羟色胺2A受体拮抗作用，可以调节5-羟色胺信号的传递。
这种拮抗作用有助于恢复5-羟色胺系统的平衡，从而改善情绪和认知功能。
3. 右佐匹克隆片的受体亲和性右佐匹克隆片对不同受体具有不同程度的亲和力，在临床上起到了治疗精神障碍的效果。
3.1 多巴胺D2受体右佐匹克隆片对多巴胺D2受体具有高亲和力，这是其主要的作用机制之一。
通过拮抗多巴胺D2受体，右佐匹克隆片可以减少多巴胺信号的传递，从而改善精神分裂症的阳性症状。
3.2 5-羟色胺2A受体右佐匹克隆片对5-羟色胺2A受体也具有高亲和力。
这种亲和力使得右佐匹克隆片能够调节5-羟色胺系统的功能，并改善情绪和认知功能。
3.3 其他受体除了多巴胺D2受体和5-羟色胺2A受体，右佐匹克隆片还对其他多巴胺和5-羟色胺受体具有一定的亲和力，如多巴胺D1、D3、D4、5-羟色胺1A、1B、6等。
文献医疗综述撰写模板
• 结语 参照文件（共25篇）
二、文件综述旳内容与形式
• 内容能够是对一种领域，一种学术分支、 一种专题、一种学说、一种措施甚至一 种仪器旳综述。篇幅可大可小，要根据 题目旳主要性，文件资料旳多少和作者 旳能力而定。一般为参照文件十几至几 十篇，不超出一万字。
• 形式:
一般首先简要概述本题目旳来龙去脉。 正文一般将内容分列小标题，注明引用旳 文件出处（在引文末尾右上用角标注明该文件 在本综述旳文件目录中旳序号）。在篇尾要有 一简短总结性文字（涉及某些展望性意见、值 得进一步研究旳方面、今后旳趋势等）。 文末，按顺序附一种全部引用了旳文件旳 目录，一文件至少要列出第一作者旳姓名，论 文题目，期刊名（用缩写），年份、卷、页。
6．所列参照文件书写格式：
文件类型标识符 专著[M], 期刊[J] ，学位论文[D]，专利[P]
专著[M]
[序号] 编著者. 专著名称[M]. 版次（第1版可省略）. 出版地： 出版者，出版 年. 起页~止页.
[1] Pocock SJ. Clinical Trials[M]. 2nd ed. New York: John Wiley & Sons Ltd, 1984. 110~22
• 4. 拟出写作提要：
提要应该有主要旳小标题，以及在相应小标 题下拟论述或讨论旳详细方面和问题，准备引用 旳文件，总结与展望等。
• 5．再次查阅文件：
• 6．下笔写作：
可先一气呵成，不必在写作中间过分推敲用词 等。到全文写毕，再去逐段推敲较为合适。
四、写文件综述时旳注意事项
• 1. 所引用旳文件应该亲自读过原著全文，不可 只根据摘要即加以引用，更不可间接引用（即 引用由文件引用旳内容而并未见到被引用旳原 文），
氨法烟气脱硫工程中环境检测分析方法标准的思考与建议
化学工艺领域脱硫，氨法脱硫工程中控制环保及性能指标为二氧化硫、氮氧化物、颗粒物、氨、硫酸雾等，主要环境检测分析方法如表1所示。
表1 氨法脱硫工程中主要环境检测分析方法标准颗粒物固定污染源排气中颗粒物测定与气态污染物采样方法固定污染源废气低浓度颗粒物的测定重量法GB/T 16157—1996HJ 836—20172 氨法脱硫工程中环境检测分析方法标准存在的问题2.1 测试方法争议和问题汇总在氨法脱硫工程实施过程中，现有检测方法是否能较好地反映污染物排放情况，环境监测部门和相关被监测企业也发现一0 引言国内外主流烟气脱硫技术为石灰石-石膏湿法脱硫[1]，而氨法脱硫具有反应速率快，吸收剂利用率高，脱硫效率高，原料丰富，副产品经济价值高且运行稳定等优点，有一定市场占有率。
氨法烟气脱硫工艺应用工程中普遍存在在吸收塔出口气溶胶颗粒物排放浓度大的缺陷[2-3]，这些气溶胶颗粒会随着烟气排入大气，危害了环境和人身的健康，针对氨法脱硫烟气中气溶胶排放的问题，国内学者进行了实验室与实践中研究[4-6]，以往研究重点主要关注脱硫性能及性能研究测试，而针对检测方法及检测指标间相互影响的研究较少。
本文根据氨法脱硫尾气特点及检测标准内容进行探讨，分析氨法烟气脱硫工程中主要检测分析方法标准存在的问题和不足，针对存在的问题，建议从加快标准修订，合理增加检测指标，使标准更具有实用性和指导性，以推动氨法脱硫工程及检测分析方法标准的建设与发展。
1 氨法脱硫工程中主要环境检测分析方法标准氨法脱硫最早从硫酸工业尾气处理上发展而来，20世纪70年代，Krou Kroers 公司开发出氨-硫酸铵法脱硫工艺[7]。
随后这种工艺被不断改进和完善，进入20世纪90年代，氨-硫酸铵法脱硫工艺逐步得到推广应用，2010年我国发布了第一个氨法脱硫工程技术规范《火电厂氨法脱硫工程技术规范氨法》，2014年发布了《冶金烧结团球烟气氨法脱硫设计规范》，2016年发布了《铝电解烟气氨法脱硫脱氟除尘技术规范》，2018年发布了《氨法烟气脱硫工程通用技术规范》，氨法脱硫主要应用于氨法烟气脱硫工程中环境检测分析方法标准的思考与建议徐广标(云南佳测环境检测科技有限公司，云南 昆明 650032)摘要：文章研究了氨法烟气脱硫工程环境检测分析方法标准的现状，结合当前氨法烟气脱硫工程特点及检测标准内容，分析氨法烟气脱硫工程中主要检测分析方法标准存在的问题和不足，针对存在的问题，建议加快标准修订，合理增加检测指标，使标准更具有实用性和指导性，以推动环境检测分析方法标准的建设与发展。
民族药理学作者须知
JOURNAL OF ETHNOPHARMACOLOGYAn Interdisciplinary Journal Devoted to Indigenous DrugsAUTHOR INFORMATION PACK TABLE OF CONTENTS• Description• Audience• Impact Factor• Abstracting and Indexing • Editorial Board• Guide for Authors p.1p.2p.2p.2p.2p.4ISSN: 0378-8741DESCRIPTIONThe Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people's use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.In recent years the preservation of local knowledge, the promotion of indigenous medical systems in primary health care, and the conservation of biodiversity have become even more of a concern to all scientists working at the interface of social and natural sciences but especially to ethnopharmacologists. Recognizing the sovereign rights of States over their natural resources, ethnopharmacologists are particularly concerned with local people's rights to further use and develop their autochthonous resources.Accordingly, today's ethnopharmacological research embraces the multidisciplinary effort in the:• documentation of indigenous medical knowledge,• scientific study of indigenous medicines in order to contribute in the long-run to improved health care in the regions of study, as well as• search for pharmacologically unique principles from existing indigenous remedies.The Journal of Ethnopharmacology publishes original articles concerned with the observation and experimental investigation of the biological activities of plant and animal substances used in the traditional medicine of past and present cultures. The journal will particularly welcome interdisciplinary papers with an ethnopharmacological, an ethnobotanical or an ethnochemical approach to the study of indigenous drugs. Reports of anthropological and ethnobotanical field studies fall within the journal's scope. Studies involving pharmacological and toxicological mechanisms of action are especially welcome. Clinical studies on efficacy will be considered if contributing to the understanding of specific ethnopharmacological problems. The journal welcomes review articles in the above mentioned fields especially those highlighting the multi-disciplinary nature of ethnopharmacology. Commentaries are by invitation only.AUDIENCEEthnopharmacologists, Medicinal Chemists, Pharmacologists, Toxicologists, Anthropologists, Pharmacognosists, Ethnobotanists, Economic Botanists, EthnobiologistsIMPACT FACTOR2014: 2.998 © Thomson Reuters Journal Citation Reports 2015ABSTRACTING AND INDEXINGAGRICOLABIOSISCambridge Scientific AbstractsChemical AbstractsCurrent Contents/Life SciencesMEDLINE®International Pharmaceutical AbstractsEMBASENAPRALERT (Natural Products Alert)Science Citation IndexCAB AbstractsScopusEMBiologyEDITORIAL BOARDEditor-in-Chief:R. Verpoorte, Gorlaeus Lab., Universiteit Leiden, Einsteinweg 55, 2333 CC, Leiden, NetherlandsDeputy Editor-in-ChiefA.M. Viljoen, Tshwane University of Technology, Pretoria, South AfricaAssociate Editor:D. Guo, Chinese Academy of Sciences (CAS), Shanghai, ChinaA.K. Jäger, University of Copenhagen, Copenhagen O, DenmarkG. Lin, Chinese University of Hong Kong, Hong Kong, Hong KongP.K. Mukherjee, Jadavpur University, Kolkata, IndiaG. Schmeda Hirschmann, Universidad de Talca, Talca, ChileA. Shikov, Saint Petersburg Institute of Pharmacy, Kuzmolovo P 245, Russian FederationE. Yesilada, Yeditepe University, Erenkoy-Istanbul, TurkeyReviews Editor (including Commentaries and Book Reviews):M. Heinrich, The School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK If you want to suggest a review, please provide a structured abstract and include an annotated table of contents and a short CV of the lead author(s).Managing Editor:B. Pomahacova, Leiden University, Leiden, NetherlandsI. Vermaak, Tshwane University of Technology, Pretoria, South AfricaM. Sandasi, Tshwane University of Technology, Pretoria, South AfricaL.J. McGaw, University of Pretoria, Pretoria, South AfricaEditorial Board:S. Alban, Kiel, GermanyM.J. Balick, Bronx, New York, USAR. BauerG. Bourdy, Cayenne, French GuianaJ.B. Calixto, Florianópolis, BrazilC-T. Che, Hong Kong, Hong KongG.A. Cordell, Evanston, Illinois, USAV.S. da Silva Bolzani, Araraquara, BrazilJ. Ding, Shanghai, ChinaV.M. Dirsch, Vienna, AustriaE. Elisabetsky, Porto Alegre, BrazilJ. Fleurentin, Metz, FranceB.L. Furman, Glasgow, UKM.P. Germano, Messina, ItalyJ. Gertsch, Bern, SwitzerlandA.H. Gilani, Karachi, PakistanM.P. Gupta, Panama City, PanamaA. Hensel, Münster, GermanyP.J. Houghton, London, UKZ. Ismail, Penang, MalaysiaW. Jia, Kannapolis, North Carolina, USAT. Johns, Ste. Anne de Bellevue, Quebec, Canada A.K. Jäger, Copenhagen O, DenmarkG. Kavalali, Istanbul, TurkeyH-S. Kim, Cheongju, South KoreaJ. Kim, Seoul, South KoreaY. Kimura, Ehime, JapanM.A. Lacaille-Dubois, Dijon, FranceM. Leonti, Cagliari, ItalyE. Matteucci, Pisa, ItalyI. Merfort, Freiburg, GermanyJ.J.M. Meyer, Pretoria, South AfricaD.E. MoermanD.A. Mulholland, Guildford, England, UKA. Panthong, Chiang Mai, ThailandX. Peigen, Beijing, ChinaA. Pieroni, Pollenzo/Bra, ItalyD.D. Soejarto, Chicago, Illinois, USAE. Speroni, Bologna, ItalyA.J. Vlietinck, Antwerpen, BelgiumH. Wagner, München, GermanyC.S. Weckerle, Zurich, SwitzerlandC.W. Wright, Bradford, UKS. Zacchino, Rosario, ArgentinaFounding Editors:J.G. BruhnL. Rivier, Lausanne, SwitzerlandGUIDE FOR AUTHORSINTRODUCTIONThe Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people's use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people, confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.Please note that figures and tables should be embedded in the text as close as possible to where they are initially cited. It is also mandatory to upload separate graphic and table files as these will be required if your manuscript is accepted for publication.Classification of your paperPlease note that upon submitting your article you will have to select at least one classification and at least three of the given keywords. You can preview the list of classifications and keywords (here). This information is needed by the Editors to more quickly process your article. In addition to this, you can submit free keywords as described below under "Keywords".The "rules of 5"The Editors and Editorial Board have developed the "Rules of 5" for publishing in JEP. 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Outlines for potential reviews need to include: A detailed abstract using the structure provided in the guidelines An annotated table of contents A short CV of the lead author5. Book reviews - Books for review should be sent to the Reviews Editor.6. Commentaries - invited, peer-reviewed, critical discussion about crucial aspects of the field but most importantly methodological and conceptual-theoretical developments in the field and should also provide a standard, for example, for pharmacological methods to be used in papers in the Journal of Ethnopharmacology. The scientific dialogue differs greatly in the social / cultural and natural sciences, the discussions about the common foundations of the field are ongoing and thepapers published should contribute to a transdisciplinary and multidisciplinary discussion. The length should be a maximum of 2-3 printed pages or 2500 words. Please contact the Reviews Editor j.ethnopharmacol@ with an outline.7. Conference announcements and news.BEFORE YOU BEGINEthics in publishingFor information on Ethics in publishing and Ethical guidelines for journal publication see /publishingethics and /journal-authors/ethics. Policy and ethicsIn the covering letter, the author must also declare that the study was performed according to the international, national and institutional rules considering animal experiments, clinical studies and biodiversity rights. See below for further information. The ethnopharmacological importance of the study must also be explained in the cover letter.Animal and clinical studies - Investigations using experimental animals must state in the Methods section that the research was conducted in accordance with the internationally accepted principles for laboratory animal use and care as found in for example the European Community guidelines (EEC Directive of 1986; 86/609/EEC) or the US guidelines (NIH publication #85-23, revised in 1985). 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有机化学实验中关于过柱的实验方法和技巧
关于过柱的实验方法和技巧(注意：有机溶剂对身体特有害别是心肺；肝脏等所有过柱操作都要在通风橱里进行！！常说的过柱子应该叫柱层析分离，也叫柱色谱。
我们常用的是以硅胶或氧化铝作固定相的吸附柱。
由于柱分的经验成分太多，所以下面我就几年来过柱的体会写些心得，希望能有所帮助。
1、柱子可以分为：加压，常压，减压压力可以增加淋洗剂的流动速度，减少产品收集的时间，但是会减低柱子的塔板数。
所以其他条件相同的时候，常压柱是效率最高的，但是时间也最长，比如天然化合物的分离，一个柱子几个月也是有的。
减压柱能够减少硅胶的使用量，感觉能够节省一半甚至更多，但是由于大量的空气通过硅胶会使溶剂挥发（有时在柱子外面有水汽凝结），以及有些比较易分解的东西可能得不到，而且还必须同时使用水泵抽气（很大的噪音，而且时间长）。
以前曾经大量的过减压柱，对它有比较深厚的感情，但是自从尝试了加压后，就几乎再也没动过减压的念头了。
加压柱是一种比较好的方法，与常压柱类似，只不过外加压力使淋洗剂走的快些。
压力的提供可以是压缩空气，双连球或者小气泵（给鱼缸供气的就行）。
特别是在容易分解的样品的分离中适用。
压力不可过大，不然溶剂走的太快就会减低分离效果。
个人觉得加压柱在普通的有机化合物的分离中是比较适用的。
2、关于柱子的尺寸，应该是粗长的最好柱子长了，相应的塔板数就高。
柱子粗了，上样后样品的原点就小（反映在柱子上就是样品层比较薄），这样相对的减小了分离的难度。
试想如果柱子十厘米，而样品就有二厘米，那么分离的难度可想而知，恐怕要用很低极性的溶剂慢慢冲了。
而如果样品层只有厘米，那么各组分就比较容易得到完全分离了。
当然采用粗大的柱子要牺牲比较多的硅胶和溶剂了，不过这些成本相对于产品来说也许就不算什么了（有些不环保的说，不过溶剂回收重蒸后也就减小了部分浪费）。
现在见到的柱子径高比一般在1：5～10，书中写硅胶量是样品量的30～40倍，具体的选择要具体分析。
如果所需组分和杂质分的比较开（是指在所需组分rf 在～，杂质相差以上），就可以少用硅胶，用小柱子（例如200毫克的样品，用2cm×20cm的柱子）；如果相差不到，就要加大柱子，我觉得可以增加柱子的直径，比如用3cm的，也可以减小淋洗剂的极性等等。
急性胰腺炎实验室诊断相关指标对病情评估及诊治意义
急性胰腺炎实验室诊断相关指标对病情评估及诊治意义研究生伊力亚斯·托合提尼亚孜指导教师亚力坤.赛来副教授专业学位领域急诊医学（急诊外科学）研究方向急危重症病研究2019年3月Singificance of laboratory diagnostic indicators in ptients with acute pancreatitisＡDissertation Submitted toXinjiang Medical UniversityIn Partial Fullfillment of the Requirementsfor the Degree ofMaster of MedicineByYiliyasi TuohetiniyaziEmergency MedicineDissertation Supervisor:A/Prof.Yalikun SailaiMarch,2019中英文缩略词对照表英文缩写英文全名中文译名AP acute pancreatitis急性胰腺炎APACHEIIacute physiology andchronic health evaluationII急性生理和慢性健康状况评分CRP C-Reactive ProteiH：C反应蛋白MAP mild acutepancreatitis轻症急性胰腺炎MSAP moderately severeacute pancreatitis中重症急性胰腺炎SAP severe acutepancreatitis重症急性胰腺炎SIRSsystemicinflammatory responsesyn-drome全身炎症反应综合征目录1摘要……………………………………………………………………………………2 ABSTRACT………………………………………………………………………………3前言……………………………………………………………………………………4研究内容与方法………………………………………………………………………………4 1研究对象.…………………………………………………………………………………2内容与方法………………………………………………………………………44 3统计学方法.…………………………………………………………………………6结果……………………………………………………………………………………………8讨论……………………………………………………………………………………19小结……………………………………………………………………………………20致谢……………………………………………………………………………………21参考文献……………………………………………………………………………………综述 (22)攻读硕士学位期间发表的学位论文 (36)导师评阅表 (37)急性胰腺炎实验室诊断相关指标对病情评估及诊治意义研究生：伊力亚斯.托合提尼亚孜导师：亚力坤.赛来副教授/主任医师摘要目的：通过文献研究比较血清学指标，探讨急性胰腺炎（AP）实验室诊断和评价急性胰腺炎患者临床评价和临床价值的理想指标。
演示文稿精细化工产品导论药物与中间体
R1
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主要的强心苷类心血管药物
名称 洋地黄毒苷 异羟基洋地黄毒苷
毛花苷C 毒毛旋花子苷-K
羊角拗苷 铃兰毒苷
有机硝酸酯
有机硝酸酯类属于一氧化氮供体药物(NO donors drug),是经典的血管扩张剂 包括有机硝酸酯类、亚硝酸酯类及亚硝酸硫醇酯类 作用:主要用于治疗心绞痛，药物代谢动力学特点是 吸收快，起效快。
N *
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R-构型：镇静剂，无致畸作用 S-构型：无镇静作用，致畸变
图13：沙利度胺的另一个对映体可 导致 严重的致畸性。
沙利度胺的S-异构体可导
1957年～1962年，造 成数万名婴儿严重畸形。
进一步研究表明，其 致畸作用是由沙利度胺其 中的一个异构体（S-异构 体）引起的，而R-构型即 使大剂量使用，也不会引 起致畸作用
药效团基本概念的提出，指导通过简化、改造天然 药物的化学结构，发展了作用相似、结构简单的合 成药物。如对古柯碱的结构改造，1890年发现了具 有局麻作用的苄佐卡因（对氨基苯甲酸乙酯），进 一步结构改造，导致了普鲁卡因的发现。
本世纪初，德国Ehrlich（1909年）发现胂凡钠 明能治疗锥虫病和梅毒，从而开始用合成药物治 疗传染病；
本类药物主要包括硝酸酯类的硝酸甘油和硝酸异山 梨醇酯及硝酸异戊四醇酯，亚硝酸类的亚硝酸异戊 酯等
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世界卫生组织儿童标准处方集
WHO Model Formulary for ChildrenBased on the Second Model List of Essential Medicines for Children 2009世界卫生组织儿童标准处方集基于2009年儿童基本用药的第二个标准目录WHO Library Cataloguing-in-Publication Data:WHO model formulary for children 2010.Based on the second model list of essential medicines for children 2009.1.Essential drugs.2.Formularies.3.Pharmaceutical preparations.4.Child.5.Drug utilization. I.World Health Organization.ISBN 978 92 4 159932 0 (NLM classification: QV 55)世界卫生组织实验室出版数据目录：世界卫生组织儿童标准处方集基于2009年儿童基本用药的第二个标准处方集1．基本药物 2.处方一览表 3.药品制备 4儿童 5.药物ISBN 978 92 4 159932 0 (美国国立医学图书馆分类：QV55)World Health Organization 2010All rights reserved. Publications of the World Health Organization can be obtained fromWHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: ******************). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the aboveaddress(fax:+41227914806;e-mail:*******************).世界卫生组织2010版权所有。
食管癌早癌内镜黏膜下剥离术后发生食管狭窄的危险因素分析及预测模型建立
第 44 卷第 9 期 2023 年 9 月安徽医学Anhui Medical Journal食管癌早癌内镜黏膜下剥离术后发生食管狭窄的危险因素分析及预测模型建立苏娇娇 谢园园 孙全静 刘晓燕［摘 要］ 目的 分析食管癌早癌内镜黏膜下剥离术（ESD ）后发生食管狭窄的危险因素并建立相应的预测模型。
方法 回顾性分析六安市人民医院消化内科于2018年6月至2021年12月收治的52例符合标准的早期食管癌患者病理和临床资料，根据患者术后是否发生食管狭窄分为狭窄组（n =15例）与非狭窄组（n =37例）。
比较两组患者基线资料，分析筛选获得与术后发生食管狭窄有关的指标，再将有关指标纳入多因素logistic 回归分析中得出影响术后发生食管狭窄的独立因素，并基于上述因素对应系数构建线性回归模型，采取受试者工作特征（ROC ）曲线评估模型的预测价值，选择拟合优度检验评判预测值与实际值的一致性情况。
结果 两组患者固有肌层损伤、病变环周范围、肿瘤浸润深度、剥离的纵径长度比较，差异有统计学意义（均P <0.05）。
多因素logistic 回归分析结果提示有固有肌层损伤（OR =4.310，95%CI ：2.307～8.055）、病变环周范围>3/4环周（OR =12.820，95%CI ：3.781～43.470）、肿瘤浸润深度进展至M3～SM1期（OR =6.482，95%CI ：2.747～15.294）、长剥离的纵径长度（OR =1.091，95%CI ：1.037～1.148）均为影响ESD 术后发生狭窄的独立危险因素（P <0.05）。
根据多因素分析结果得出的常量与各个危险因素对应的相关系数构建预测模型：Logit （P ）=1.461×固有肌层损伤（0表示无固有肌层损伤，1表示有固有肌层损伤）+2.551×病变环周范围（0表示病变环周范围≤3/4环周，1表示病变环周范围>3/4环周）+1.869×肿瘤浸润深度（0表示肿瘤浸润深度为M1～M2期，1表示肿瘤浸润深度为M3～SM1期）+0.087×剥离的纵径长度（实测值）-2.637。
卡达尔健康肾上腺素产品说明书
R e a g e n t sALT/GPT ReagentTHERMO SCIEnTIFIC - AlT is found primarily in the liver and kidneys . Increased levels of AlT are generally a result of liver disease associated with some degree of hepatic necrosis such as cirrhosis, carcinoma, viral or toxic hepatitis and obstructive jaundice . Slight to moderate elevations have been observed after administration of medications such as nSAIDS, antibiotics, antiepileptic drugs, statins or opiates .ūIntended for the in vitro quantitative determination of Alanine Aminotransferase in serumūReagent is suitable for manual use or on automated clinical chemistry analyzersūApplications for a wide range of automated analyzers are available on requestSpecifications:linearity . . . . . . . . . . . . . . . . . . . . . . .0 - 450 U/l (TR71121)Stability . . . . . . . . . . . . . . . . . . . . . . .12 Stable liquid (TR71121)Cat. No.Mfr. No.DescriptionQty.B5358-178TR71121Infinity AlT/GPT 2 x 125ml2/eaAmmonia ReagentTHERMO SCIEnTIFIC - Excess ammonia exerts toxic effects on the central nervous system . Elevated levels of ammonia may be either due to inborn errors of metabolism or secondary to other conditions . Elevated ammonia may be observed in advanced liver disease caused by Reye’s syndrome, viral hepatitis or cirrhosis .Cat. No.Mfr. No.DescriptionQty.B5358-170TR60101Ammonia 2 x 28ml2/eaAST/GOT ReagentTHERMO SCIEnTIFIC - AST is widely distributed with high concentrations in the heart, liver, skeletal muscle and kidney . Damage or disease to any of these tissues such as myocardial infarction, viral hepatitis, liver necrosis, cirrhosis and muscular dystrophy may result in raised serum levels of AST .ūIntended for the in vitro quantitative determination of aspartate aminotransferase in serum or plasmaūReagent is suitable for manual use or on automated clinical chemistry analyzersūApplications for a wide range of automated analyzers are available on requestSpecifications:linearity . . . . . . . . . . . . . . . . . . . . . . .0 - 450 U/lStability . . . . . . . . . . . . . . . . . . . . . . .Stable liquid (TR70121)Cat. No.Mfr. No.DescriptionQty.B5358-175TR70121Infinity AST/GOT 2 x 125ml2/eaCalcium ReagentTHERMO SCIEnTIFIC - Thermo Scientific Calcium Reagent is intended for the in vitro quantitative determination of calcium in serum or plasma .Cat. No.Mfr. No.DescriptionQty.–1265-250Infinity Calcium Arsenazo 2 x 125ml2/ea– To order, call your customer service representative and provide them with Mfr. No.。
国内中国期刊的英文缩写
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我国人群有机磷阻燃剂暴露评估及其健康风险
基准剂量为 0.21 ng·mL-1(5-OH-EHDPP)及 0.93 ng·mL-1(4-OH-TPHP),我国人群暴露 EHDPP 和 TPHP 导致血液总胆固醇浓度 升高的健康风险分别为 2.72% 和 0.80% 。 关键词: 有机磷阻燃剂;血液总胆固醇升高;内暴露评估;健康风险分析 文章编号: 1673-5897(2021)3-155-11 中图分类号: X171.5 文献标识码: A
我国人群有机磷阻燃剂暴露评估及其健康风险
张晓华, 赵繁荣, 胡建英*
地表过程分析与模拟教育部重点实验室,北京大学城市与环境学院,北京 100871
收稿日期:2021-04-12 录用日期:2021-04-13
摘要: 有机磷阻燃剂的使用量呈现不断增加的趋势,但目前对我国人群有机磷阻燃剂的暴露特征及其健康风险研究甚少。 为 评估有机磷阻燃剂的暴露水平,本研究采集了全国 8 个城市中共 600 名普通成年人的尿液样本,用 LC-MS-MS 检测了 11 种有 机磷酸酯代谢产物的浓度。 研究表明,11 种代谢产物均在尿液当中检出,磷酸二(2-氯乙基)酯(BCEP)的检出率及检出浓度最 高,我国人群尿液样品中有机磷酸酯代谢产物浓度及组成特征呈现区域性差异,8 个城市的总浓度范围在 5.80 ~ 26.28 ng· mL-1 之间,深圳市以磷酸二丁酯(DnBP)为主要检出物质,其余地区以 BCEP 为主要检出物质,芳香类有机磷酸酯的代谢产物 在深圳市的浓度比例高于其他 7 个城市。 对 8 个城市检出率>60% 的 6 种有机磷酸酯代谢产物尿液浓度数据的归一化处理表 明,2-乙基-5-羟基己基二苯基磷酸酯(5-OH-EHDPP)、4-羟基苯基二苯基磷酸酯(4-OH-TPHP)、磷酸二(2-氯乙基)酯(BCEP)、磷酸 二(1,3 -二氯异丙基)酯(BDCIPP)、磷酸二丁酯(DnBP)和磷酸二苯酯(DPHP)的全国浓度几何均值分别为(0 .03 ± 2 .75 )、(0 .08 ± 2 .77 )、
环磺酮原药专题研究报告 (一)
环磺酮原药专题研究报告 (一)环磺酮原药专题研究报告一、引言环磺酮，又称硫呋嘌呤，是用于治疗类风湿性关节炎等炎症疾病的重要药物。
据悉，环磺酮原药在我国市场上的销售量居于前列。
然而，在环磺酮原药的生产过程中，存在一系列的问题，这些问题极大地限制了环磺酮原药的质量和效果。
为了深入了解环磺酮原药的存在问题和解决方案，本文撰写了一份环磺酮原药专题研究报告。
二、环磺酮原药的生产流程环磺酮原药的生产流程主要包含以下几个环节：1、原料采购环磺酮的原料多为蒜苷，山葵甙等植物提取物，而这些提取物的品质对环磺酮的质量和效果有着重要的影响。
因此，原料采购要求原料的产地、生长环境、采收时间、提取方法等方面必须符合国家相关标准。
2、制备硫代醛硫代醛是环磺酮原料中的重要中间体，合理制备硫代醛有利于提高环磺酮的产率和纯度。
目前硫代醛的主要制备方法是采用硫与烯烃反应制备而成。
但由于反应条件难以控制，不少厂家采用的是经验性操作，导致硫代醛含量低、杂质多的情况。
3、环磺酮的合成环磺酮的合成是环磺酮原药生产中的重要环节，其关键点在于硫代醛的选择性氧化。
目前大多数厂家采用的氧化剂是氯代苯钠，但氯代苯钠的制备方法要求严格，不少生产企业无法保证氯代苯钠的含量和质量。
4、提纯和包装环磺酮在合成后需要进行多次提纯，使其达到目标纯度。
在提纯过程中，厂家需掌握一系列复杂的操作参数，如温度、相对湿度、压力、流速等。
而在包装环节，厂家也需注重环保问题，不能使用对环境有害的材料。
三、环磺酮原药存在的问题1、原材料挑选不确信由于环磺酮原料大多数来源于植物提取物，而这些提取物的含量、品质因原料选取、制造公司使用技术而有很大差异性。
2、硫代醛制备不规范硫代醛的生产需要精密的反应控制，厂家往往难以掌控反应过程，从而导致硫代醛含量低、杂质多的情况。
3、氧化剂品质不稳定氯代苯钠，作为环磺酮原药生产中的重要氧化剂，其制备和使用过程中容易受到环境等因素的影响，品质不稳定。
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Euthyphro
What is piety?
Universal – a abstract concept, category such as piety, justice.
Particular – individual cases that may be classified as a part of a universal.
“Dog” refers to all species that fall into this category. They may be identified by s pecific properties that make them a dog.
“My dog” is a particular thing that can be classified as a dog, a creature, a mammal, a poodle. All of these categories are abstracts or universals.
Attempt 1 (p. 5):
Euthyphro is trying to define a universal such as piety in terms of a particular. A pious thing is to prosecute somebody for murder and an impious thing is not to.
Attempt 2 (p.7):
What is pleasing to the gods is pious.
Attempt 3 (p. 11):
What is pleasing to all the gods is pious.
Please know the refutation of the first two attempts.
The main issue:
(1) Do the gods love piety because it is pious,
or
(2) is it pious because the gods love it?
Euthyphro Question rephrased: Does God like morality because it is good or is morality good because God says so?
(1) Objective Moral Theory – moral values exist outside of God(s) and humans, where both God(s) and humans are subject to it.
Ex: Murder is wrong for both humans and God(s).
(2) Divine Command Ethics – moral values are determined by God(s).
Ex: If God(s) says murder is right, it is right.
A. Piety is pious
B. The gods love it.
C. Piety is loved by the gods
B is a necessary premise for C.
From here it follows:
If A then B.
If B then C
Therefore, If A then C, i.e. If Piety is pious then the gods love it. Hence, gods love piety because it is pious.
Piety is pleasing to the gods is one of the things that are pleasing to them. There are other things that are pleasing to them that are not pious.
Still this is not a definition but only an attribute or a characteristic of piety; that is that the gods love it.
Attempt 4 (p. 14):
∙Piety is a part of justice.
∙All things that are pious are just but not all things that are just pious.
∙Piety is that part of justice that has to do with the gods, and the other part of justice has to do with people.
∙Euthyphro’s 4th attempt restated, “…if any man knows that his words and actions in prayer and sacrifice are acceptable to the gods, that is what is pious; and it
preserves the state , as it does private fam ilies.” (p. 18)
∙Piety is a science of prayer and sacrifice.
∙Piety is a science of asking of the gods and giving to them.
∙The gifts that the gods receive from humans are honor and praise in the course of prayer and sacrifice.
∙These gifts are loved by the gods.
∙Piety means that which is loved by the gods.
Hence, piety is pious because the gods love it.。