OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

Cultivating and inspiring students’ interests in performing experiments and improving students’ diagnostic skills and scientific research capability for infectious diseases like malaria are critical to comprehensive experimental teaching of morphology. Consequently, Soochow University initiated a problem-based hands-on inquiry-based comprehensive experiment program of blood-borne protozoa infections and diagnosis, which took students in the “5 + 3” integrated program of clinical medicine as the teaching targets, and it consisted of three parts: pre-class, in-class, and post-class. Before the experimental curriculum, students learned the theoretical knowledge and the process of modeling Plasmodium berghei and Babesia microti infections in mice through online course and virtual simulation experiments, and during the experimental curriculum, students performed exploratory experiments on differential diagnosis of P. berghei and B. microti infections with pathogenic and serological tests. After the experimental curriculum, students performed molecular biological testing and extracurricular scientific research project training through open experiments. A questionnaire survey was conducted among 99 students in the “5 + 3” integrated training program of clinical medicine in batch 2021, and a total of 93 valid questionnaires were retrieved, with a questionnaire recovery rate of 93.94%. Questionnaire survey showed that 70.97% (66/93), 70.97% (66/93), 77.42% (72/93), 70.97% (66/93), and 83.87% (78/ 93) of the students strongly agreed with the five statements in the questionnaire respectively, namely “high interest in learning during the experiment”, “reasonable experimental content settings and good classroom atmosphere”;, “teachers were good at guiding students’ practice and thinking”, “students were the main body of the classroom during the experiment” and “Comprehensive experiments had better teaching effects than traditional verification experiments”, indicating that the problem-based hands-on inquiry-based comprehensive experiment teaching has enhanced students’ learning interest, spirit of inquiry, innovative thinking, and teamwork ability.

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

Objective:To investigate the risk of falls in patients with Parkinson's disease and establish and validate a prediction model.Methods:We selected 372 patients with Parkinson's disease at Sichuan Nanchong Mental Health Centre from January 2022 to Septem-ber 2023.The patients were divided in a 7:3 ratio into model group(260 cases)and validation group(112 cases).According to previ-ous literature and suspected factors found in clinical practice,we collected general information(sex,age,etc.)and disease-related factors(the duration of Parkinson's disease,the type of medications taken,etc.)that may be associated with falls in patients with Parkinson's disease.In the model group,between patients with and those without falls within 1 year as reported by the patients or their family members,potential predictors for falls were determined through comparison of general information and disease-related factors,least absolute shrinkage and selection operator(LASSO)regression,and multivariable logistic regression.Based on the significant factors,a nomogram model was established and validated.Results:In the model group,81(31.15%)of the 260 patients experienced falls.According to the LASSO regression and multivariable logistic regression results,alcohol consumption,the type of medications,the score of the Unified Parkinson's Disease Rating Scale part Ⅲ(UPDRS-Ⅲ),the Berg Balance Scale score,the presence of arthritis,and the presence of osteoporosis were independent factors influenc-ing falls in patients with Parkinson's disease.The area under curve(AUC)of the receiver operator characteristic curve(ROC)for pre-dicting the risk of falls in patients with Parkinson's disease was 0.896(95%CI=0.856-0.935)in the model group and 0.883(95%CI=0.840-0.926)in the validation group.The calibration curve analysis results showed that the prediction curves of the model and valida-tion groups closely fitted the standard curves.The decision curve analysis results indicated that when the probability threshold for pre-dicting the fall risk in Parkinson's disease using the nomogram was 0.10-0.90,the net benefit rate of the patients was greater than 0.Conclusion:The risk of falls in patients with Parkinson's disease are mainly influenced by factors such as alcohol consumption and the type of medications.The nomogram model established in this study can be used to predict the fall risk in patients with Parkinson's disease.

Objective To explore the underlying mechanisms by which time-restricted feeding(TRF)attenuates dextran sodium sulfate(DSS)-induced colitis in mice via modulation of regenerating islet-derived protein 3 gamma(Reg3γ)expression and gut microbiota.Methods Six-week-old C57BL/6 mice were stratified by body weight and randomized into ad libitum feeding(AL)and TRF groups(n=7).The AL mice were given unrestricted food access,whereas the TRF mice were allowed feeding only during 00:00 and 08:00 daily,for totally 4 weeks.Mouse colitis model was induced at the fourth week by adding 2.5%dextran sodium sulfate(DSS)in drinking water for 6 d.Disease severity and the effects of TRF were assessed with disease activity index(DAI)scoring,colon length measurement,HE staining and histopathological scoring,and mRNA expression levels of regenerating islet-derived 3 gamma(Reg3g)and inflammatory cytokines in colonic tissues.Another 14 mice were randomized into AL plus antibiotic cocktail(AL+ABX)and TRF plus antibiotic cocktail(TRF+ABX)groups,with 7 animals in each group.ABX was administered to deplete gut microbiota and evaluate the microbiota dependence of TRF in attenuating colitis.Fecal samples from AL and TRF mice were analyzed by 16S ribosomal RNA sequencing(16S rRNA-seq),and serum lipopolysaccharide(LPS)level was measured.The colonic epithelial cells were collected for RNA-seq.Results After modeling,the AL mice exhibited typical colitis symptoms,such as weight loss,diarrhea,and hematochezia.TRF intervention significantly attenuated these above symptoms,with lower DAI scores from day 4 post-modeling(P<0.001),reduced colon shortening(P<0.01),preserved tissue architecture,and decreased inflammation.RT-qPCR analysis showed that TRF down-regulated colonic mRNA expression levels of Reg3g and pro-inflammatory cytokines(IL-1 β,IL-6,TNF-α)(P<0.05)while up-regulated that of anti-inflammatory factor IL-10(P<0.000 1)when compared with the corresponding levels in AL mice.ABX treatment led no significant differences between the AL+ABX and TRF+ABX groups in term of DAI score,colon length,or histopathology.Obviously down-regulated Reg3g was observed in the TRF+ABX group than the AL+ABX group(P<0.05),whereas L-1β,IL-6,TNF-α and IL-10 showed no notable changes.16S rRNA-seq revealed that TRF markedly reshaped gut microbiota composition,with increased Gram-positive bacterial abundance,reduced Gram-negative bacteria,with concomitant lower serum LPS level(P<0.001).RNA-seq also indicated significant suppression of NF-κB and other inflammation-related signaling pathways in the TRF group.Conclusion TRF attenuates DSS-induced colitis in mice by downr-egulating Reg3γ expression,reshaping gut microbiota,and reducing serum LPS level,and thereby suppressing NF-κB-mediated inflammatory signaling pathways.

Objective To explore the predictive value of combined detection of serum CXC chemokine lig-and 12(CXCL12),caspase-cleaved cytokeratin 18(CCCK-18)and matrix metalloproteinase-9(MMP-9)for short-term poor prognosis in patients with acute hemorrhagic stroke.Methods A total of 138 patients with a-cute hemorrhagic stroke admitted to a hospital from October 2021 to March 2023 were selected as the study objects.Serum CXCL12,CCCK-18 and MMP-9 levels were detected after admission and before treatment.Pa-tients were followed up for 6 months after treatment and were divided into good prognosis group and poor prognosis group according to the modified Rankin scale score.Clinical data and serum CXCL12,CCCK-18 and MMP-9 levels of the two groups were compared to analyze the factors affecting the short-term poor prognosis of patients with acute hemorrhagic stroke.Receiver operating characteristic(ROC)curve was drawn to evalu-ate the predictive value of single and combined detection of serum CXCL12,CCCK-18 and MMP-9 in patients with acute hemorrhagic stroke.Results Among 138 patients,there were 52 cases in the poor prognosis group and 86 cases in the good prognosis group,and the poor prognosis rate was 37.68%.Serum CXCL12,CCCK-18 and MMP-9 levels,age,blood loss at admission,National Institutes of Health Stroke Scale(NIHSS)score at admission,systolic blood pressure and diastolic blood pressure at admission in the poor prognosis group were higher than those in the good prognosis group.The score of Glasgow Coma Scale(GCS)at admission was lower than that of good prognosis group,and the difference was statistically significant(P<0.05).Multivari-ate Logistic regression analysis showed that high level of serum CXCL12,high level of CCCK-18,high level of MMP-9,older age,large amount of blood loss upon admission,high NIHSS score and high systolic blood pres-sure were all risk factors for short-term poor prognosis of acute hemorrhagic stroke(P<0.05).High GCS score on admission was a protective factor(P<0.05).ROC curve analysis showed that the area under the combined prediction curve of serum CXCL12,CCCK-18 and MMP-9 was higher than that of the single and pairwise combined prediction of each index(P<0.05).Conclusion The combined detection of serum CX-CL12,CCCK-18 and MMP-9 has a good value in predicting the short-term poor prognosis of patients with a-cute hemorrhagic stroke.

Based on the core collection retrieval of the Web of Science database,researches related to the medicinal field of plant-derived vesicles(PDVs)were retrieved.The research hotspots and their changes in the pharmaceutical field of PDVs are visually analyzed by using bibliometric software VOSviewer and CiteSpace.A detailed discussion is held around the author,institution,country,key research hotspots and annual develop-ment hotspots,revealing the current research status of PDVs in the pharmaceutical field and predicting future trends,which provides valuable perspectives for researchers to understand the current research status of PDVs in the pharmaceutical field and discover possible unexplored areas in this field.

Radiotherapy is a crucial component of the treatment of tumors. In addition to directly causing DNA damage in tumor cells and inducing cell apoptosis, radiotherapy is also involved in the regulation of systemic immune status. Increasing evidence indicates that radiotherapy can remodel the tumor immune microenvironment (TIME) and reverse the immunosuppressive state, thereby enhancing anti-tumor effects and demonstrating stronger immune responses and therapeutic benefits when combined with immune checkpoint inhibitors. Taking lung cancer as an example to explore the impacts and potential mechanisms of radiotherapy on the TIME and anti-tumor immunity, which can provide a scientific basis for optimizing the treatment strategies of lung cancer.

Objective To explore the effect of Osthole on neuroinflammation in Alzheimer's disease(AD)by regulating the lactylation of pyruvate kinase M2(PKM2).Methods(1)Animal experiments:18 mice were divided into three groups,namely wild-type(WT)group,APP/PS1 group and APP/PS1+Osthole group.Learning-and memory-related biobehavioral indicators were compared among the three groups.Immunohistochemistry was used to detect the positive expression of Iba1 in brain tissue,enzyme-linked immunosorbent assay(ELISA)was employed to detect the levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β in brain tissue,and Western Blot was used to detect the protein expression levels of Pan lactylation(Pan-kla)and PKM2 lactylation(PKM2-kla)in brain tissue.(2)Cell experiments:an in vitro AD model was constructed by treated in mouse microglia(BV2 cells)with LPS/Aβ1-42,and followed by treatment with Osthole.Cell viability was detected by methyl thiazolyl tetrazolium(MTT),expression of Iba1(a marker of microglial activation)was detected by Western Blot,nitric oxide(NO)production was assessed by Griess reagent,and levels of IL-6,TNF-α and IL-1β were detected by ELISA.BV2 cell-conditioned medium(CM)was co-cultured with neuroblastoma cells(Na2 cells)to assess the protective effect of Osthole on Na2 cells.(3)Molecular docking was performed between Osthole and PKM2,and experimental verification was conducted.Results In animal experiments,deficits of learning and memory in mice were aggravated in APP/PS1 group compared with that in WT group,which were improved upon treatment with Osthole.Furthermore,the APP/PS1 group mice showed an increase in Iba1 positive cells in brain tissue,an increase in the levels of pro-inflammatory factors IL-6,TNF-α and IL-1β,as well as an increase in the levels of Pan-kla and PKM2-kla compared with the WT group,while the above indexes were inhibited by the Osthole treatment.In cell experiments,Osthole had no significant effect on BV2 cell viability at concentrations up to 100 μmol/L.Treatment with LPS/Aβ1-42 upregulated the expression of Iba1,NO production,and levels of pro-inflammatory factors IL-6,TNF-α,and IL-1β in BV2 cells,while Osthole significantly inhibited the expression of these LPS/Aβ1-42-induced indicators.Meanwhile,Osthole attenuated the damage of BV2-CM on Na2 cells.The molecular docking results indicated a good binding affinity between Osthole and PKM2.Treatment with Osthole can down-regulated the levels of lactate,Pan-kla and PKM2-kla in the AD cell model.Conclusion Osthole can improve the condition of AD and reduce neuroinflammation by inhibiting the lactylation of PKM2.