ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Diabetes mellitus, characterized by glucose metabolism disorders and marked by insulin deficiency or insulin resistance, has seen a continuous rise in prevalence. In recent years, islet transplantation has matured as a therapeutic approach for diabetes, becoming an important method for glycemic control and the reduction of diabetes-related complications. Donor selection directly influences transplant outcomes, and various research institutions worldwide have proposed multiple scoring systems to optimize donor assessment, such as the University of Alberta scoring system and the North American Islet Donor Score. This article explores the impact of key factors such as donor age, body mass index and ischemia time on islet transplantation. Combining practical experience in pancreatic donor selection from Shanghai Changzheng Hospital, it proposes screening criteria for pancreatic donors suitable for China, aiming to provide new evidence for improving the success rate of islet transplantation.

Objective:This study aims to explore the risk factors of Multi-center Investigator-Initiated Clinical Trials (MIITs), and provide a basis for developing study management strategies.Methods:The original draft of MIIT risk evaluation factors was determined through literature analysis and internal discussions of the research group. Thirty five experts were consulted using the Delphi method, and then the MIIT risk evaluation elements were finally determined. Analytic Hierarchy Process (AHP) was used to calculate the weights of each index.Results:The recovery rates of both rounds of expert consultation were 100%, and the degree of expert authority was 0.856. The study ultimately formed an MIIT risk evaluation framework consisting of three first-class indexes, twelve second-class indexes, and thirty-eight third-class indexes. The weight values of the first-class indexes (start-up period, implementation period, and summary period) were 0.209 8, 0.710 6, and 0.079 6, respectively. Meanwhile, the weight values of the second-class indexes and third-class indexes were determined.Conclusions:Exploring the risk evaluation factors of MIIT provides valuable insights into identifying critical risk points, which, in turn, contributes to enhancing MIIT management efficiency, research progress, and quality.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Objective:This study aims to explore the risk factors of Multi-center Investigator-Initiated Clinical Trials (MIITs), and provide a basis for developing study management strategies.Methods:The original draft of MIIT risk evaluation factors was determined through literature analysis and internal discussions of the research group. Thirty five experts were consulted using the Delphi method, and then the MIIT risk evaluation elements were finally determined. Analytic Hierarchy Process (AHP) was used to calculate the weights of each index.Results:The recovery rates of both rounds of expert consultation were 100%, and the degree of expert authority was 0.856. The study ultimately formed an MIIT risk evaluation framework consisting of three first-class indexes, twelve second-class indexes, and thirty-eight third-class indexes. The weight values of the first-class indexes (start-up period, implementation period, and summary period) were 0.209 8, 0.710 6, and 0.079 6, respectively. Meanwhile, the weight values of the second-class indexes and third-class indexes were determined.Conclusions:Exploring the risk evaluation factors of MIIT provides valuable insights into identifying critical risk points, which, in turn, contributes to enhancing MIIT management efficiency, research progress, and quality.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Missed diagnosis can often be noted in mild traumatic brain injury (mTBI), resulting from atypical symptoms, diverse performances and subjectively dependent report. Blood biomarkers can not only reflect the pathophysiological process of mTBI to a certain extent, but also have important clinical value in assessing brain injury severity and predicting adverse outcomes. This article systematically describes the research progress of blood biomarkers that can assist mTBI diagnosis, distinguish CT manifestations and predict prognoses in recent years, aiming to provide references for clinical application of blood biomarkers in mTBI.

Objective To investigate the changes in serum levels of claudin-5 and Apelin-13 in patients with depression and their relationship with disease progression and sleep disorders.Methods A total of 128 patients with depression admitted to our hospital from June 2021 to July 2023 were selected as the study group,and another 128 patients who underwent physical examinations during the same period were selected as the control group.The correlation between the expression levels of serum claudin-5 and Apelin-13 in patients with depression and the Hamilton Depression Rating Scale(HAMD)score,as well as the diagnostic value of serum claudin-5 and Apelin-13 for the severity of depression in patients were analyzed.Results The expression level of claudin-5 in the serum of patients in study group was higher than that of the control group,which increased with the severity of the disease(P<0.05)and was positively correlated with the HAMD score(r=0.713,P<0.05).In addition,the expression level of claudin-5 in the serum of patients with sleep disorders was higher than that of those without sleep disorders(P<0.05),and the trend of changes in the expression level of Apelin-13 was opposite;Age,age at onset of depression,and claudin-5 were factors for sleep disorders in patients with depression,while Apelin-13 was a protec-tive factor(P<0.05);The combined detection of serum claudin-5 and Apelin-13 is superior to their individual detection(Z combined detection-claudin-5=2.393,Z combined detection-Apelin-13=1.964,P=0.016,0.044).Conclusion The expression levels of claudin-5 and Apelin-13 in serum of patients with depression were related to the progression of disease and the sleep disorders and the combined detection has high diagnostic value for severe depression.

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

ObjectiveTo systematically review the intervention effect of Chinese medicine on the structure and function of testicular Sertoli cells in animal models of impaired spermatogenesis. MethodThe databases， such as China National Knowledge Infrastructure （CNKI），VIP，Wanfang Data，EMbase，and Pubmed，were searched for experimental studies on the effect of Chinese medicine on the structure and function of testicular Sertoli cells in animal models with impaired spermatogenesis. The included studies were evaluated for risks of bias，and the outcome indicators were analyzed with RevMan and Stata software. ResultThirty studies were included，involving 37 randomized controlled trials （RCTs）. As indicated by the Meta-analysis results， compared with the model group，Chinese medicine increased sperm density（SMD=2.42，95% confidence interval（CI）［1.47，3.37］，P<0.000 01）， promoted sperm motility（SMD=2.35，95%CI ［1.70， 2.99］，P<0.000 01）， up-regulated the protein and mRNA levels of Vimentin （related to Sertoli cell cytoskeleton）， elevated the levels of Occludin and Claudin-11 （related to tight junction of blood-testis barrier）， boosted the levels of β-catenin and N-cadherin （related to adherens junction of blood-testis barrier）， raised the level of connexin 43 （Cx43， related to gap junction of blood-testis barrier）， improved the function of Sertoli cells， increased the serum content of Inhibin B （INHB）， and up-regulated the levels of testicular follicle-stimulating hormone receptor （FSHR）， INHB mRNA， androgen-binding protein （ABP） mRNA， transferrin（TF），stem cell factor（SCF），SCF mRNA，glial cell line-derived neurotrophic factor （GDNF），GDNF mRNA，bone morphogenetic protein 4（BMP4），and BMP4 mRNA （P<0.05）. ConclusionChinese medicine can effectively increase sperm density and motility of animal models of impaired spermatogenesis，and improve the structure and function of testicular Sertoli cells. However，affected by the quality of the included studies，the above conclusion needs to be further verified by relevant high-quality studies.