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.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.

Na⁺/H⁺ antiporter (NHX) gene subfamily plays an important role in plant response to salt stress. In this study, we identified the NHX gene family members of Chinese cabbage and analyzed the expression patterns of BrNHXs gene in response to abiotic stresses such as high temperature, low temperature, drought and salt stress. The results showed that there were 9 members of the NHX gene family in Chinese cabbage, which were distributed on 6 chromosomes respectively. The number of amino acids was 513-1 154 aa, the relative molecular weight was 56 804.22-127 856.66 kDa, the isoelectric point was 5.35-7.68. Members of BrNHX gene family mainly existed in vacuoles, the gene structure is complete, and the number of exons is 11-22. The secondary structures of the proteins encoded by the NHX gene family in Chinese cabbage had alpha helix, beta turn and random coil, and the alpha helix occurred more frequently. Quantitative real-time PCR (qRT-PCR) analysis showed that the gene family members had different responses to high temperature, low temperature, drought and salt stress, and their expression levels differed significantly in different time periods. BrNHX02 and BrNHX09 had the most significant responses to these four stresses, and their expression levels were significantly up-regulated at 72 h after treatments, which could be used as candidate genes to further verify their functions.
Genome, Plant ; Multigene Family ; Stress, Physiological/genetics* ; Brassica/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism*

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.

OBJECTIVE： To establish the fingerprint of the ethanol e xtract from Melastoma dodecandrum ， to study spectrum-effect relationship of its antioxidant activity. METHODS ：HPLC method and Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）were used to establish the fingerprints of 15 batches of ethanol extracts from M. dodecandrum，and heir similarity was evaluated. The common peaks were identified by comparing with substance control. DPPH free radical scavenging method ，ABTS free radical scavenging method and total antioxidant capacity determination method （FRAP） were used to determine antioxidant activity in vitro of 15 batches of ethanol extracts from M. dodecandrum . Principal component analysis，bivariate correlation analysis and partial least squares regression analysis were used to study the spectrum-effect relationship of the antioxidant activity of the ethanol extracts from M. dodecandrum . RESULTS ：Totally 20 common peaks were identified in HPLC fingerprints of 15 batches of ethanol extracts from M. dodecandrum ；its similarity with the control fingerprint was not less than 0.831；it was identified that peak 3 was gallic acid ，peak 13 was vitexin ，peak 17 was rutin and peak 19 was ellagic acid. The IC 50 values of DPPH radical scavenging method of 15 batches of ethanol extracts from M. dodecandrum were 21.98-57.87 μ g/mL，that of ABTS radical scavenging method were 40.94-101.88 μ g/mL，the results of FRAP method were 0.19-0.48 mg/mL. Principal component analysis showed that the contribution rate of IC 50 variance of DPPH was 80.77％. Bivariate correlation analysis showed that the peak areas of peak 2 （positive correlation ） and peak 11 （negative correlation ） were significantly correlated with antioxidant activity （P＜0.05）；partial least squares regression analysis showed that ，the variable projection importance （VIP）in descending order was peak 11＞peak 2＞peak 16＞peak 15＞peak 12＞peak 13＞peak 18，and their VIP values were greater than 1. Peaks 2，13，15，16 and 18 were positively correlated with antioxidant activity ，and peaks 11 and 12 were negatively correlate d with antioxidant activity ，and the absolute value of standardized regression coefficient were greater than 0.1. CONCLUSIONS ：Fifteen batches of ethanol extracts of M. dodecandrum have antioxidant activity in vitro . The compounds corresponding to common peaks 2，11，12， 13，15，16 and 18 may be the material basis of antioxidant activity of M. dodecandrum .

Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats.Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ,35 mg/kg) in spontaneous hypertensive rats (SHR).Diabetic rats were divided into diabetic group and the Irbesartan treated group.The pathological changes were investigated by fluorescence microscope and electron microscope.The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose.The concentration of angiotensin Ⅱ in the supernatant was detected by radioimmunoassay.Immunofluorescence staining was performed to detect the co-localization of CD31 and FSP1.Results The significant myocardial fibrosis was presented in the diabetic group.Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats.Double staining of HAEC showed co-localization of CD31 and FSP1,which was decreased by the treatment of Irbesartan (P ＜ 0.05).When HAEC was exposed to high glucose,it showed some cells acquired spindle-shaped morphology and lost CD31 staining,and FSP1 and α-SMA protein expression levels were markedly upregulated,which attenuated by the treatment of Irbesartan.Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats.

Objective To investigate the effects of low density lipoprotein receptor (LDLr) pathway on podocyte injury in diabetic nephropathy (DN) under inflammatory stress.Methods Male db/db mice and db/m mice were randomly divided into four groups (8 mice in each group):db/m group (control),casein injected db/m group (db/m + casein),db/db group (db/db),and casein injected db/db group (db/db + casein).An inflamed model of DN was established according to our previous study.24-hour urinary protein was measured every week.The plasma lipid profile was detected by clinical biochemistry assay.Podocyte changes were evaluated by electron microscope and immunofluorescent staining.Lipid accumulation in the kidney was evaluated by oil red O staining and intracellular cholesterol quantitative assay.The protein expression of Wilm's tumor-1 (WT-1),nephrin,α-smooth muscle actin (t-SMA),and molecules correlated with LDLr pathway were examined by immunohistochemical staining or Western blotting.The colocalized protein expression of LDLr with WT-1 was examined by immunofluorescent staining and laser confocal microscopy.Results There were no differences in plasma levels of LDL and HDL among four groups.Compared with db/db group,the db/db+ casein group showed markedly increased 24-hour urinary protein,more significant podocyte foot process effacement and podocyte damage,increased lipid droplet accumulation in kidneys,increased protein expressions of LDLr,SCAP and SREBP-2 in kidneys (all P ＜ 0.05).Interestingly,increased LDLr protein expression in kidneys of db/db mice was negatively correlated with decreased nephrin protein expression (r =-0.855,P ＜ 0.01) and positively correlated with increased α-SMA protein expression (r=0.768,P ＜ 0.01).Conclusions The disruption of LDLr pathway induced by inflammation contributes to podocyte injuries in diabetic nephropathy.

Objective A preliminary study was conducted on the measuring tool for teachers' attitude in the medical schools towards curriculum integration of medical program.Methods Literature review and expert interview were conducted to design a questionnaire which comprised 56 items to investigate teachers' attitude towards medical curriculum integration.The method of factor analysis and Pearson correlation coefficient were used to evaluate structure validity,the content validity index I-CVI and S-CVI were used to evaluate the content validity and Cronbach's alpha coefficient and split-half reliability were used to evaluate the reliability of the questionnaire.Results Three principal components were extracted by factor analysis,which explained 59.219％ of the total variance.After rotation,the factors 1-3 were respectively defined as value recognition,participation initiative and emotional tendency.Cronbach's alpha coefficient of the three factors and all the items is 0.922,0.903,0.728 and 0.862 respectively.Conclusion The reliability and validity of the measurement tool is acceptable,and can be used as a reference for similar domestic survey

Obj ective To compare yhe effecys of ywo enyeral nuyriyion payhways in Geriayric ICU payienys receiving mechanical venyilayion as well as adopyion of effecyive care measures in order yo provide a basis for implemenyayion of enyeral nuyriyion feeding in yhese payienys.Methods A case-conyrol syudy was used.Fifyy ICU payienys receiving mechanical venyilayion were randomly divid-ed inyo nasogasyric yube group and nasoinyesyinal yube group,25 cases for each.Boyh group received proper nursing measures.The yime of achieving yargey dose of nuyriyion,nuyriyion improvemeny in 2,3,4 weeks and yhe incidence of complicayions were analysed.Results The yime of achieving yargey dose in nasoinyesyinal yube group was significanyly less yhan yhose in nasogasyric yube group (P<0.05).Afyer 4-weeks yreaymeny,yhe levels of yoyal proyein,serum prealbumin and yransfer-rin were improved in boyh groups wiyh a significanyly greayer degree in nasoinyesyinal yube group (P<0 .05 ).The incidence of complicayions in nasoinyesyinal yube group is significanyly less yhan yhose in nasogasyric yube group (P<0 .05 ).Conclusion Nasoinyesyinal yube feeding combined wiyh proper nursing measures in elderly ICU payienys receiving mechanical venyilayion makes yhe yargey dose of nuyriyion easily achieved and reduces yhe incidence of complicayions of mechanical venyilayion such as aspirayion and abdominal disyension.

Obj ective To compare yhe effecys of ywo enyeral nuyriyion payhways in Geriayric ICU payienys receiving mechanical venyilayion as well as adopyion of effecyive care measures in order yo provide a basis for implemenyayion of enyeral nuyriyion feeding in yhese payienys.Methods A case-conyrol syudy was used.Fifyy ICU payienys receiving mechanical venyilayion were randomly divid-ed inyo nasogasyric yube group and nasoinyesyinal yube group,25 cases for each.Boyh group received proper nursing measures.The yime of achieving yargey dose of nuyriyion,nuyriyion improvemeny in 2,3,4 weeks and yhe incidence of complicayions were analysed.Results The yime of achieving yargey dose in nasoinyesyinal yube group was significanyly less yhan yhose in nasogasyric yube group (P<0.05).Afyer 4-weeks yreaymeny,yhe levels of yoyal proyein,serum prealbumin and yransfer-rin were improved in boyh groups wiyh a significanyly greayer degree in nasoinyesyinal yube group (P<0 .05 ).The incidence of complicayions in nasoinyesyinal yube group is significanyly less yhan yhose in nasogasyric yube group (P<0 .05 ).Conclusion Nasoinyesyinal yube feeding combined wiyh proper nursing measures in elderly ICU payienys receiving mechanical venyilayion makes yhe yargey dose of nuyriyion easily achieved and reduces yhe incidence of complicayions of mechanical venyilayion such as aspirayion and abdominal disyension.