Common problems and suggestions of biological sample management in drug clinical trials / 中国药房

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Determination of polymyxin B concentration in plasma and its application in critically ill patients / 中国药房

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

Common protocol deviations and improvement methods and precautions in drug clinical trials / 中国药房

OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.

Status quo and countermeasures of job mobility among clinical research coordinator/clinical research associate in Chongqing / 中国药房

OBJECTIVE To investigate the job mo bility of cl inical research coordinators （CRCs） and clinical research associates（CRAs）in Chongqing ，and to explore the feasible methods to improve the job stability of CRCs and CRAs. METHODS Questionnaire survey was conducted to investigate the job mobility of 200 CRCs and CRAs working in 22 drug clinical trial institutions of Chongqing. The contents included basic information ，job mobility ，and reasons for mobility. RESULTS & CONCLUSIONS Totally 178 valid questionnaires were recovered ，with an efficient recovery rate of 89.00％，of which 110 were recovered from CRCs and 68 were recovered from CRAs. Among the surveyed CRCs and CRAs ，the age distribution was mainly 20-30 years old ，accounting for 87.27％ and 82.35％ of the respective population respectively. The overall educational degree of CRAs were slightly higher than those of CRCs. The majors and previous work experience were mainly related to medicine ；the proportion of other non-medicine-related professions who switched to CRCs was higher than that of CRAs. Totally 88.18％ had CRC working experience within 3 years；after having 1-＜3 years of work experience ，50.00％ had worked in 2 or more work units. Totally 64.70％ had CRA working experience within 3 years；after having 1-＜3 years of work experience ，70.37％ had worked in 2 or more work units. CRCs handled 5.38 items of clinical trials and completed 1.22 items on average ；CRAs handled 7.47 items and completes 2.04 items on average. Main reasons of CRCs and CRAs for job-hopping included low salary below expectations，few promotion opportunities ，and too much workload ，accounting for 83.64％/80.88％，45.45％/39.71％，31.82％/ 26.47％，respectively. As an important part of clinical trials ，CRCs and CRAs had high job mobility. It is suggested to establish a unified industry standard ，standardize the management rights and responsibilities of CRCs and CRAs ，optimize the working mode of CRCs and CRAs ，and improve professional identity and sense of belonging ，so as to improve the job stability of relevant

Discussion on the Classification ，Selection and Management of Antibacterial Drugs in Medical Institution ：From the Adjustment of 2019 Edition of National Basic Medical Insurance List / 中国药房

OBJECTIVE：To provi de reference for classification ，selection and management of antibacterial drugs in medical institutions. METHODS ：The adjustment of antibacterial drug list in 2019 edition of National Basic Medical Insurance ，Work Injury Insurance and Maternity Insurance （called“New List ”for short ）was introduced. The politic reference of selection and adjustment of antibacterial drugs and the principle of classification selection in medical institutions were sort out. The challenges which may bring to pharmaceutical administration and clinical use in medical institutions were investigated. RESULTS & CONCLUSIONS： Three new varieties of the antibacterial drugs in the New List have been added ，including Doxycycline injection，Faropenem granules and Metronidazole oral regular-release preparations. Nine product specifications were excluded ，such as Tetracycline oral regular-release preparations ，Dirithromycin oral regular-release preparations ，etc. The limitation of indications and/or indications of 19 regulations was modified ，and some antibacterial requirements were limited to patients with clear evidence of drug sensitivity test or severe infection. When classifying and selecting antibacterial drugs ，medical institutions should take the existing policy documents as the basis ，strictly implement the relevant provisions of antibacterial drug management ，give priority to meeting various national prescription sets and drug list varieties ，select drugs with sufficient evidence-based treatment basis ，drug quality and safety ，and take into account the convenience and economy of drug use ，supply guarantee service capacity of drug production and circulation enterprises and local situation of pathogenic bacteria resistance. The adjustment of New List also brings challenges to use and management of antibacterial drugs in medical institutions. For example ，New List emphasizes“limited drug sensitivity evidence ”for many antibacterial specifications. But if the clinicians choose drugs mechanically according to the drug sensitivity results and ignores the experience treatment in anti-infection treatment ，another type of “abuse”may be abused ；in addition，the indications of myxomycetin B and colistin （sulfate myxomycetin ）are completely different ，which also deserves further study.

Analysis of Clinical Distribution and Drug Resistance of Acinetobacter baumannii in a Third-grade Class-A Hospital from Chongqing during 2015 to 2018 / 中国药房

OBJECTIVE：To provide reference for clinical treatment of Acinetobacter baumannii infection and rational use of antibiotics. METHODS ：By retrospective analysis ，64 500 strains of bacteria were isolated from the inpatients of our hospital during Jan. 2015 to Dec. 2018. WHONET 5.6 software was used to analyze the detection rate ，specimen type ，departments of A. baumannii. The resistance of A. baumannii to 18 commonly used antibiotics in 4 years was analyzed by RxC table χ 2 test. RESULTS：A total of 2 072，2 040，2 017 and 2 143 strains of A. baumannii were isolated during 2015-2018，accounting for 12.85％，13.38％，13.60％，11.71％ of positive specimens. The main specimen types of 8 272 strains of A. baumannii were sputum（4 368 strains，52.81％），pus（1 106 strains，13.37％），ascites（804 strains，9.72％）. The main departments were burn department（1 605 strains，19.40％），hepatobiliary department （1 200 strains，14.51％），brain surgery department （977 strains， 11.81％）. The drug resistance rate to 18 kinds of antibiotics showed a wave-like decreasing trend （P＜0.001）. In 2018，drug resistance rate to ampicillin and aztreonam was more than 80％，and that to ampicillin/sulbactam ，ceftazidime，levofloxacin， Compound sulfamethoxazole ，gentamicin，amikacin，tobramycin and tegacyclin was less than 50％ ，among which the drug resistance rate to amikacin and tegacyclin were 14.7％ and 0，respectively. CONCLUSIONS ：There is no significant change in the number of isolates and detection rate of A. baumannii in our hospital between 2015 and 2018. The bacteria mainly cause respiratory tract infection. Amikacin or tegacyclin are recommended for treatment.

Influence and Reflections on the Work of Drug Clinical Trial Institutions in China after Joining in ICH / 中国药房

OBJECTIVE： To summarize the problems and countermeasures which the construction of drug clinical trial institutions face after China Food and Drug Administration （CFDA） join in ICH， and its effects on clinical study management in China. METHODS： Combined with the experience on Good Clinical Practice （GCP） in our hospital during recent years， reviewing related content of ICH-GCP， the differences between China’s GCP （CFDA-GCP） and ICH-GCP， the problems faced by drug clinical trial institutions after joining in ICH， and the thinking of China’s clinical research were discussed. RESULTS & CONCLUSIONS： There were differences between CFDA-GCP and ICH-GCP in the management concept of clinical drug trials， the structure and function of ethical committees， the protection of the rights and interests of subjects， the choice of researchers and research institutions， management requirements of experimental drugs and the management of documents and data. After joining in ICH， the current organization and management structure， system and standard operating procedures， ethics committee， GCP training and continuing education， professional quality control system， experimental drug management， data management and information system construction and upgrading， clinical research coordinator management and other aspects of the drug clinical trial institutions were far from the requirements of ICH. The standardization of drug clinical trial institutions in China can be further promoted by revising regulations and guidelines， formulating standard operating procedures in line with ICH-GCP， building standardized ethics committees， implementing GCP training and continuing education， improving quality control system and drug management in clinical trials， strengthening hardware and software construction and clinical coordinator management， etc. At the same time， problems such as fewer full-time personnel and weak implementation of the system can be improved by strengthening project management， improving the quality of employees and building normal cross-regional cooperation.

Talking about the Key Points and Notices of Drug Management in Clinical Trials / 中国药房

OBJECTIVE： To provide references for improving the standard operating procedures of drug management in clinical trials and drug management in clinical trials. METHODS： According to Good Clinical Practice （GCP）， Data On-site Verification Points of Drugs Clinical Trial， Qualification Examination Rules of Drug Clinical Trial Institution， based on the quality control project carried out in our hospital since July 2016， the matters needing attention in the non-standard operation and key process of drug management in clinical trial were summarized， and the improvement measures were discussed. RESULTS & CONCLUSIONS： Non-standard drug management is a high-incidence link of non-standard operation in the trial process. Among them， the acceptance， distribution and use of drugs are the three links with the highest incidence of non-standard operation of drug management in the trial process. Therefore， when formulating the relevant management system， each institution should pay attention to it according to its own situation； such as， when accepting drugs in clinical trials， attention should be paid to checking the intact degree of drug packaging； drugs transported in cold chain should also be checked for temperature records and rejected in case of over-temperature； the copies of the waybill should be kept in file with the original to avoid fading of the thermosensitive paper； whether the relevant characteristics of the control drugs and placebos meet the requirements. Institutions can standardize the key links of drug management in the trial process， the time of project establishment， project start-up， quality control and supervision， formulate and constantly improve the relevant drug management system and standard operating procedures （SOP）. For example， when starting a project， attention should be paid to the participation of drug administrators in the training and signature of start-up meeting， whether the design of the form is complete， standardized and operable. It is necessary for clinical trial institutions to pay attention to the standardization and precision of drug management and the key links in clinical trials.

Preliminary Discussion on Common Problems of Non-Registered Clinical Research Programs from the Perspective of Ethical Review:An Analysis of Ethical Review Samples in a Third-Class A Hospital in the Past Ten Years / 中国医学伦理学

This paper analyzed the non-registered clinical research program of ethical review in a third-class hospital from 2008 to 2017, and found that the common problems of the program mainly focused on the imprecise standards of inclusion and exclusion, the lack of basis for determining sample size, the unreasonable setting of observation indicators, the insufficient research background, the lack of necessary basis for topic setting, and the lack of privacy and confidentiality provisions. The reasons were as follows: the lack of ethical awareness of researchers, inadequate ability to design clinical research programs, and insufficient attention to program formulation. It is suggested that clinical researchers should pay more attention to the formulation of the program, and properly handle the relationship between scientific research and ethics while consolidating the foundation of scientific research.

Retrospect and Prospect:Analysis of Knowledge Mapping Domain of Ethics Committee Study in China / 中国医学伦理学

Through the development of close to 30 years,ethics committee has become an indispensable part of biomedical research involving human beings.The research into ethics committee is problem-orientated and has made rich research results from theoretical research to practical research.By using software CiteSpace Ⅲ and analytic visualization of CNKI literature as measuring and drawing tool,this paper made the mapping knowledge domain of ethics committee study since 1991 and found that the published articles amount showed a wave upward trend,the quantity increased sharply in recent years and the research focused on ethical review,clinical trial,informed consent,human subjects,etc.The research topics developed from macro level to micro level and fitted with the development of whole ethical practice.The existing research mainly focused on five aspects of the analysis of laws and regulation,multidisciplinary perspective analysis of ethics committees,the management and practice,the review mechanism and supervision and evaluation.The existing research lacked many summaries accordance with China's national condition;the theory was separate from practice;the research on the micro-level was less.With the development of ethics committee in China,the ethics research on micro-level will become the focus of next step.

Verification of analytical measurement range of serum creatinine detected by Roche Cobas 501 Biochemistry Analyzer / 国际检验医学杂志

Objective To investigate how the clinical laboratory conducting the verification of analytical measurement range (AM R) of quantitative items detected by the biochemical analyzer according to the requirements of the international standards by verifying the serum creatinine AMR for ensuring the accuracy and reliability of detection results .Methods The enzyme method was adopted to detect the 7‐concentration levels test specimens of CAP linear range proficiency test on the Roche Cobas 501 biochemical analyzer .These 7 specimens target values covered the low ,middle and high values of creatinine AMR marked by the manufacturer′s instructions .Each specimen was detected twice and the mean value was taken ,then the bias between the mean value and target value was calculated .In addition ,referring to the requirements of CLSI guiding document EP6‐P ,the patients′fresh serum contai‐ning high value creatinine was collected ,then mixed with certain proportion and centrifuged .The mixture concentration was calcu‐lated and served as the high value specimen(H) ,and the low value specimen was obtained by the same treatment .Then the high and low value specimens were dispensed with the relations of 5L ,4L+1H ,3L+2H ,2L+3H ,1L+4H and 5H and formed the series specimens .The creatinine levels in each specimen was detected on the Roche Cobas 501 biochemical analyzer ,each specimen was de‐tected 4 times .The obtained data were performed the regression analysis .Results The bias of 7‐level CAP specimen and target val‐ue was less than the allowable error ± 7 .5% [(1/2 × TE)% ] set by the clinical laboratory of the Beijing Sanfine Hopsital .The re‐gression equation of fresh mixed serums from patients was Y =0 .988 6X+16 .614 ,b=0 .988 6 ,between 0 .97 -1 .03 ,intercept a and 0 ,ta 0 .05 ,which showed no significant difference between intercept and 0 ,the regression line was through 0 point in fact .Conclusion The verification of creatinine AMR marked by the manufacturer′s instructions is passed ,which can be adopted by the clinical laboratory .

Meta-analysis of Stroke Efficacy and Bleeding Risk of Edoxaban versus Warfarin in the Prevention of Pa-tients with Atrial Fibrillation / 中国药房

OBJECTIVE:To systematically review the effect of stroke efficacy and bleeding risk of edoxaban versus warfarin in the prevention of patients with atrial fibrillation,and provide evidence-based reference for clinical treatment. METHODS:Re-trieved from Cochrane Library,Medline,EMBase,CJFD,Wangfang Database and VIP Database,randomized controlled trials (RCT)about the stroke efficacy and bleeding risk of edoxaban versus warfarin in patients with atrial fibrillation were collected. Me-ta-analysis was performed for the incidences of stoke and excessive hemorrhage by using Rev Man 5.3 software after data extract. RESULTS:Totally 13 RCTs were included,involving 24 950 patients. Results of Meta-analysis showed,compared with warfarin group,there were no significant differences in the incidences of stoke [RR=0.97,95%CI(0.88,1.08),P=0.60] and excessive hem-orrhage [RR=0.84,95%CI(0.59,1.19),P=0.33] in edoxaban group. But the subgroup analysis showed,when daily dose of edoxa-ban was more than 30 mg,the incidence of stroke in edoxaban group was significantly lower than warfarin group [RR=0.84,95%CI(0.72,0.97),P=0.02];when it was 30 mg,the incidence of excessive bleeding in edoxaban group was significantly lower than warfarin group [RR=0.46,95%CI(0.35,0.61),P30 mg/d)of edoxaban can more effectively prevent the occurrence of stroke and low doses(30 mg/d) can reduce the risk of excessive bleeding.

Effects of inhibitory peptide of Staphylococcus epidermidis biofilm on adhesion and biofilm formation of this bacterium / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the effects of inhibitory peptide of Staphylococcus epidermidis (SE) biofilm (briefly referred to as inhibitory peptide) on adhesion and biofilm formation of SE at early stage.</p><p><b>METHODS</b>By using peptide synthesizer, the inhibitory peptide was synthesized with purity of 96.8% and relative molecular mass of 874.4. (1) Solution of SE ATCC 35984 (the same below) was cultivated with inhibitory peptide in the final concentrations of 1-256 µg/mL, and the M-H broth without bacteria solution was used as blank control. The MIC of the inhibitory peptide against SE was determined (n=3). (2) Solution of SE was cultivated with trypticase soy broth (TSB) culture solution containing inhibitory peptide in the final concentrations of 16, 32, 64, 128, and 256 µg/mL (set as inhibitory peptide groups in corresponding concentration), and solution of SE being cultivated with TSB culture medium was used as negative control group. Growth of SE was observed every one hour from immediately after cultivation (denoted as absorbance value), and the growth curve of SE during the 24 hours of cultivation was drawn, with 3 samples in each group at each time point. (3) Solution of SE was cultivated with TSB culture solution containing inhibitory peptide in the final concentrations of 16, 32, 64, 128, and 256 µg/mL (set as inhibitory peptide groups in corresponding concentration), and solution of SE being cultivated with TSB culture medium was used as negative control group. Adhesive property of SE was observed after cultivation for 4 hours (denoted as absorbance value, n=10); biofilm formation of SE was observed after cultivation for 20 hours (denoted as absorbance value, n=10). (4) Solution of SE was cultivated with TSB culture solution containing inhibitory peptide in the final concentration of 128 µg/mL (set as 128 µg/mL inhibitory peptide group), and solution of SE being cultivated with TSB culture medium was used as negative control group. Adhesive property of SE and its biofilm formation were observed with confocal laser scanning microscope (CLSM), and the sample numbers were both 3. Data were processed with one-way analysis of variance, LSD test, and Dunnett T3 test.</p><p><b>RESULTS</b>(1) The MIC of inhibitory peptide against SE exceeded 256 µg/mL. (2) There was no significant difference in the growth curve of SE between inhibitory peptide groups in different concentrations and negative control group. (3) After 4 hours of cultivation, the absorbance values of adhesive property of SE in 256, 128, 64, and 32 µg/mL inhibitory peptide groups were respectively 0.20 ± 0.04, 0.27 ± 0.03, 0.35 ± 0.04, and 0.40 ± 0.04, which were significantly lower than the absorbance value in negative control group (0.53 ± 0.10, P<0.05 or P<0.01); the absorbance value of adhesive property of SE in 16 µg/mL inhibitory peptide group was 0.47 ± 0.09, which was close to the absorbance value in negative control group (P>0.05). After 20 hours of cultivation, the absorbance values of biofilm formation of SE in 256, 128, and 64 µg/mL inhibitory peptide groups were respectively 0.49 ± 0.10, 0.68 ± 0.06, and 0.93 ± 0.13, which were significantly less than the absorbance value in negative control group (1.21 ± 0.18, P<0.05 or P<0.01); the absorbance values of biofilm formation in 32 and 16 µg/mL inhibitory peptide groups were respectively 1.18 ± 0.22 and 1.15 ± 0.26, which were close to the absorbance value in negative control group (with P values above 0.05). (4) CLSM showed that more adhering bacteria and compact structure of biofilm were observed in negative control group, but less adhering bacteria and loose structure of biofilm were observed in 128 µg/mL inhibitory peptide group.</p><p><b>CONCLUSIONS</b>The inhibitory peptide can inhibit adhesion and biofilm formation of SE at early stage, but its structure still needs to be further modified.</p>

Study on Preparation and Release in vitro of Zuojin Gastric-mucoadhesive Tablets / 中国药房

OBJECTIVE:To prepare Zuojin gastric-mucoadhesive tablets and evaluate their drug release properties in vitro. METHODS:Zuojin gastric-mucoadhesive tablets were prepared with hydroxypropyl methyl cellulose K15M(HPMC-K15M),car-bomer 934P and HPMC-E50 as the bioadhesive and matrix materials,and basic magnesium carbonate(foaming material),95% al-cohol solution(adhesive)and aerosil(glidant and lubricant)as the adjuvants. With the accumulative release of total alkaloids from Coptis chinensis Franch. at 2,6 and 10 h(Q2 h,Q6 h and Q10 h)as the indexes,orthogonal design test was conducted to optimize the amounts of HPMC-K15M,carbomer 934P,HPMC-E50 and basic magnesium carbonate,and verification was carried out. Drug re-lease properties in vitro of the preparation and Zuojin conventional tablets were observed and in vitro adhesion thereof determined. RESULTS:The optimal formulation was as follows as that for 50 tablets,HPMC-K15M of 0.7 g,carbomer 934P of 0.2 g, HPMC-E50 of 3.5 g and basic magnesium carbonate of 0.4 g. The Q2 h,Q6 h and Q10 h of three batches of prepared samples were 24.32%,56.10% and 77.04% respectively. 1-12 h drug release in vitro of prepared samples was in conformity with Ritger-Peppas equation. The Q2 h of Zuojin conventional tablets and Zuojin gastric-mucoadhesive tablets were 80.46% and 24.04%,Q12 h thereof 92.15% and 95.83% and gastric adhesion thereof 24.2 and 74.0 g/cm2,respectively. CONCLUSIONS:Zuojin gastric-mucoadhesive tablets which have sustained-release effect and adhesive property have been prepared successfully.

Clarifying the Responsibilities of Drug Clinical Trial Institution and Ethics Committee in China / 中国药房

OBJECTIVE:To clarify the responsibilities of drug clinical trial institution and ethics committee in China,and to provide reference for the improvement of drug clinical trial management. METHODS:The responsibility conflicts between drug clinical trial institution and ethics committee were summarized,and its reasons were analyzed to provide suggestions. RESULTS &CONCLUSIONS:The responsibility conflicts have been found between drug clinical trial institution and ethics committee,mainly manifesting as the essential person who submits protocol is not clear;the responsibilities in multicenter ethics investigation are con-troversial;the management of their track issues are not connected enough. 3 aspects of measures can be adopted,including reach-ing an agreement of responsibility assignment learning from foreign advanced ideas,improving laws and regulations;enhancing the management,promoting the implementation of policy and agreement. So,the responsibilities of drug clinical trial institution and ethics committee can be further clarified to improve the management of drug clinical trial.

Value of neutrophil CD64 in diagnosis of sepsis in adult patients:a meta-analysis / 中华临床感染病杂志

Objective To evaluate the application of neutrophil CD 64 in diagnosis of sepsis in adult patients.Methods Literature retrieval from PubMed, EMBASE, ISI Web of Knowledge, Cochrane Library, CBM, CNKI, CQVIP, Wanfang Data from the establishment of database to the year 2015 was conducted to identify all studies on CD 64 in diagnosis of sepsis .The quality of the literature was evaluated with the quality assessment of diagnostic accuracy studies ( QUADAS).Meta-Disc 1.4 and STATA 12.0 were used for meta analysis . Fixed-effects or random-effects model was performed based on the heterogeneity.The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were calculated .Summary receiver operating characteristic curves ( SROC ) and area under the curve (AUC) were used to evaluate the diagnostic performance of CD 64 for sepsis.Results A total of 24 studies involving 3 198 patients were included for systemic review .The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of CD 64 for diagnosis of sepsis were 0.79 (95 %CI:0.77-0.81), 0.86 (95 %CI:0.84-0.88), 7.40 (95 %CI:5.02-10.91), 0.15 (95 %CI:0.10-0.22) and 60.07 (95%CI: 29.19-123.60), respectively.The area under SROC of CD64 in diagnosis of sepsis was 0.95, and the Q* value was 0.88.Conclusion CD64 can be used to diagnose sepsis in adult patients , but it needs to be further confirmed by large multicenter studies .

Pharmacokinetics and Relative Bioavailability of Gliquidone Tablet in Volunteers / 中国药房

0.05) among these pharmacokinetic parameters. The relative bioavailability of the test preparation was(107.8?30.0)%. CONCLUSION: The test and the reference preparation are bioequivalent.

Cloning, sequencing and positioning of the encoding gene of TEM-1 ?-lactamase in Klebsiela pneumoniae / 第三军医大学学报

Objective To analyse the encoding gene of ? lactamase of the clinically isolated Klebsiela pneumoniae 99 799 and to identify its subtype. Methods The gene of ? lactamase derived from a stain of Klebsiela pneumoniae 99 799 named as was amplified by PCR. The purified PCR product was cloned into pUCm T vector and sequenced by Sanger's dideoxy chain termination composition method. Results The encoded gene of the bacterium was identified as TEM by PCR. It had the same sequence as the gene encoding TEM 1 and positioned at the 150 bp and 80 bp plasmids. Conclusion The TEM 1 ? lactamase exists in Chongqing area.