ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

OBJECTIVE: To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient. METHODS: A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)]. RESULTS: The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life. CONCLUSION Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.
Humans ; Blood Grouping and Crossmatching/methods* ; Blood Group Antigens/immunology* ; Blood Transfusion ; Male ; Isoantibodies/blood* ; Female ; Genotype

OBJECTIVE: To explore the regulatory mechanisms underlying the weak expression of ABO blood group antigens due to variants in the non-coding regions of the ABO gene. METHODS: From June 2014 to October 2023, a total of 29 samples from the Taiyuan Blood Center and local hospitals, which were serologically identified as having weak ABO antigen expression without detectable coding region mutations, were selected for this study. Full-length ABO gene sequencing was performed using third-generation long-read sequencing technology (Pacific Biosciences) to obtain complete haplotype sequences of the ABO gene. Variants in the non-coding regions were compared and identified to infer their regulatory effects on weak antigen expression. The procedures followed in this study were in accordance with the ethical standards of the World Medical Association's Declaration of Helsinki (2013 revision). The Medical Ethics Committee of Taiyuan Blood Center has granted an exemption from ethical review. RESULTS: 18 bp deletions in the -35 to -18 region of the promoter were identified in 7 samples. Variants in intron 1 (+5.8 kb) were detected in 7 samples, including ABO*A (28+5792_5793delCT (1 case) and ABO*B (28+5793T>C) located in the GATA binding region; ABO*B (28+5808C>T) (1 case) in the E-box region; and ABO*B (28+5875C>T) (4 cases) in the RUNX1 binding region. Nucleotide variants at splice sites were detected in 2 samples, namely ABO*B (C.98+1G>A) and ABO*B (C.204-2A>C). CONCLUSION Variants in the non-coding regulatory sequences of the ABO gene are a significant factor contributing to weak ABO antigen expression. In clinical ABO sequencing, it is essential to screen not only the conventional coding regions but also the flanking sequences, introns, and splice sites of the ABO gene to facilitate precise blood transfusion.
ABO Blood-Group System/genetics* ; Humans ; Alleles ; Promoter Regions, Genetic ; Haplotypes ; Introns

Objective To identify the most significantly compressed areas and the areas with the best recovery effects by analyzing the changes in vertebral height after percutaneous vertebroplasty(PVP)in patients with osteoporotic vertebral compression fractures(OVCF)through lateral radiographs.Methods A retrospective analysis was conducted on the lateral X-rays of 186 injured vertebrae from 142 patients hospitalized in our hospital's intervertebral disc center.The sagittal height of the vertebrae was measured at five different points before and after surgery,and the collected data were statistically analyzed using SPSS software.Results There were statistically significant differences in the heights of the five measured points before and after surgery within OVCF injured vertebrae(P＜0.05),in the ascending order:central＜mid-anterior＜mid-posterior＜anterior edge＜posterior edge.Comparison of the height parameters of the five measured points before and after surgery showed statistically significant differences(P＜0.01).In comparing the height restoration differences of the five measured points after PVP,the differences between central and mid-anterior,central and anterior edge,and mid-posterior and anterior edge were found not to be statistically significant(P＞0.05).The differences in height restoration for the remaining groups were statistically significant(P＜0.05),with the height restoration differences from highest to lowest being:mid-anterior,central,anterior edge,mid-posterior,posterior edge.Conclusion In patients with OVCF,the compression of the injured vertebra is most pronounced in the central part,followed by the mid-anterior part.PVP surgery can effectively restore the height of various parts of the injured vertebra,especially in the mid-anterior and central parts of the vertebral body,where the recovery effect is particularly significant.

Avian infectious bronchitis(IB),a rapidly spreading and acute disease in chickens,is caused by the infectious bronchitis virus(IBV).IB is characterized by its remarkable genetic varia-bility.IBV has a high degree of mutation,and the existing means of immunization often fail to a-chieve good results,seriously affecting the development of the domestic poultry industry.This ar-ticle offers a comprehensive review of the current understanding of the immune response to IBV,focusing on three key areas:non-specific immunity,mucosal immunity,and specific immunity.By dissecting these aspects,the aim is to provide a theoretical reference for the study of the immune mechanism of IBV.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Objective:This study aims to improve the management level and quality of horizontal scientific research contracts in hospitals, reduce the risk of contract management, and explore an efficient mode of information management of horizontal scientific research contract management.Methods:Taking a Tertiary Grade A hospital as an example, this study described and summarized the management status of horizontal scientific research contracts from 2018 to 2022, sorted out the potential risks and prevention and control nodes of the review, signing, performance, and archiving of horizontal scientific research contracts in the whole cycle management process, and designed an information management model according to the relevant elements of risk prevention and control and the standardized requirements of contract management, thereby developing information platform related functions.Results:The horizontal research contract management function of the clinical research platform based on the integration concept was available to meet the requirements of risk prevention and control of horizontal research contracts, and the contract review and signing cycle of the information management mode was shortened by 33.33% and 31.95% respectively compared with the traditional management mode. The platform realized a standardized whole process management of contract submission, review, repair and revision, signing, performance, and filing.Conclusions:Information management can effectively reduce the risk of horizontal scientific research contract management. It is necessary to strengthen the docking and interaction function with other information platforms and further explore the information auxiliary function to improve the refined management effect of horizontal scientific research contracts.

Objective:To explore the management strategies of conflicts of interest(COI) by analyzing the definition, manifestations, and implications of COI related to clinical research.Methods:This study summarized the definitions and types, manifestations, and implications of different groups of COI in clinical research. It explored the management response of medical institutions to the COI related to clinical research.Results:Conflicts of Interest could be divided into economic and non-economic conflicts of interest, showing different manifestations in different groups. COI occurs in a variety of links involved in clinical research, and the overall disclosure ratio of COI is low, which might have adverse effects on institutions, investigators, clinical research quality, and subjects.Conclusions:COI management should be implemented by strengthening the construction of the COI management system, strictly following the principle of public disclosure, and strengthening education and training, to improve the quality and credibility of clinical research.

Objective To develop the value of machine learning(ML)models based on contrast-transthoracic echocardiography(cTTE)and transesophageal echocardiography(TEE)combined with clinical and laboratory indicators for predicting patent foramen ovale-associated stroke(PFO-AS).Methods Totally 313 patients with PFO diagnosed with cTTE and TEE were retrospectively enrolled.Among them,65 cases were found complicated with ischemic stroke and confirmed as PFO-AS(PFO-AS group),and the rest 248 cases without ischemic stroke were classified as non-PFO-AS group.The patients were divided into training set(n=219,including 48 cases of PFO-AS and 171 cases of non-PFO-AS)and test set(n=94,including 17 cases of PFO-AS and 77 cases of non-PFO-AS)at the ratio of 7∶3.Univariable and multivariable logistic regression(LR)were used to analyze clinical and laboratory indicators as well as cTTE and TEE parameters in training set to screen independent predictive factors of PFO-AS.ML models,including LR,K-nearest neighbor(KNN),support vector machine(SVM),random forest(RF),decision tree(DT),back propagation neural network(BPNN)and gradient boosting machine(GBM)were constructed,and the predictive efficacy of the models for predicting PFO-AS was evaluated,then the optimal model was selected.Results Patient's age＞49-69 years,with smoking history,plasma albumin≥43.8 g/L,significant right-to-left shunt at rest shown on cTTE and complicated atrial septal aneurysm shown on TEE were all independent predictors of PFO-AS,which were used to construct ML models.The area under the curve(AUC)of LR,KNN,SVM,RF,DT,BPNN and GBM models in training set was 0.779-0.853,while in test set was 0.730-0.877.RF model had relatively high and comparable sensitivity,specificity and AUC in both training and test sets,also higher precision and smaller Brier score in test set,hence was regarded as the optimal ML model.Conclusion RF model based on cTTE and TEE combined with clinical and laboratory indicators could be used to effectively predict PFO-AS.

Objective To investigate the intervention effect of cordycepin on DCM rats and its reg-ulative effect on of AKT/GSK3β signaling pathway.Methods A total of 80 male SD rats were randomly divided into model group,cordycepin group,AKT inhibitor group and cordycepin+AKT inhibitor group,with 20 rats in each group.After the establishment of DCM model,corre-sponding intervention was given to each group.Another 20 healthy rats served as control group.Cardiac function indicators(LVEF,LVFS,LVESD,LVEDD),levels of IL-6,IL-1β,TNF-α,SOD,GSH-Px and MAD,and expression of AKT/GSK3β signaling pathway related proteins were de-termined and compared among the groups blotting.Results The model group had significantly lower LVEF and LVFS,decreased myocardial SOD and GSH-Px contents,and declined p-AKT/AKT and p-GSK3β/GSK3β,but increased LVESD and LVEDD and myocardial IL-6,IL-1β,TNF-αand MAD expression levels when compared with the control group(P＜0.05).Cordycepin treat-ment obtained increased LVEF and LVFS and myocardial tissue SOD,GSH-Px,Bcl-2,p-AKT/AKT and p-GSK3β/GSK3β protein expressions,and decreased LVESD and LVEDD and myocar-dial expression of IL-6,IL-1β,TNF-α,MAD and Bax than the model group(P＜0.05),while AKT inhibitor reversed all the changes induced by modelling(P＜0.05).Combination of cordycepin+AKT inhibitor resulted in lower LVEF,LVFS and myocardial SOD,GSH-Px,Bcl-2,p-AKT/AKT,p-GSK3β/GSK3β protein levels,and increased LVESD,LVEDD and expressions of IL-6,IL-1β,TNF-α,MAD and Bax protein in myocardial tissue when compared with cordycepin group(P＜0.05).And the combination also resulted in increases in LVEF and LVFS[(61.29±5.61)％vs(39.28±4.12)％,(39.05±3.43)％vs(24.47±2.73)％,P＜0.05]and decreases in LVESD and LVEDD(4.36±0.48 mm vs 6.97±0.69 mm,6.07±0.61 mm vs 9.02±0.85mm,P＜0.05)when compared with AKT inhibitor group.Conclusion Cordycepin improves cardiac function,myocar-dial injury,inflammation and oxidative stress in DCM rats probably by activating AKT/GSK3βsignaling pathway,and inhibits the apoptosis of cardiomyocyte.