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.

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.

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 application value of tenofovir alafenamide fumarate(TAF)in patients with first-time hepatitis B virus-related decompensated cirrhosis(HBV-DC)and its impact on renal function and lipid metabolism.Methods A total of 57 patients with first-time HBV-DC who were hospitalized and received TAF antiviral therapy in The Affiliated Hospital of Xuzhou Medical University from January 1,2020 to December 31,2022 were enrolled,and all of them received TAF antiviral therapy.Related data were collected at baseline and at weeks 12,24,and 48 of treatment,including virological and serological indicators,liver and renal function,serum phosphorus,and blood lipids.The paired t-test or single group repeated measures ANOVA were used for comparison of normally distributed continuous data,the Friedman test was used for comparison of non-normally distributed continuous data,and the chi-square test or the Fisher's exact test were used for categorical data.Results A total of 52 patients completed the 48 weeks of follow-up.After 12,24,and 48 weeks of treatment,the patients achieving HBV DNA seroconversion accounted for 38.5%,63.5%,and 84.6%,respectively;the alanine aminotransferase normalization rate were 71.2%,82.7%,and 82.7%,respectively;the proportion of the patients with Child-Pugh class A disease increased to 55.8%,73.1%,and 92.3%,respectively.Within the 48 weeks of treatment,there were significant increases in the levels of cystatin C(χ2=35.163,P＜0.001)and serum phosphorus(F=8.600,P＜0.001)and low-density lipoprotein cholesterol(χ2=10.064,P=0.018).The ratio of total cholesterol/high-density lipoprotein cholesterol decreased continuously from 3.61(2.61～5.84)to 3.27(2.70～4.36)(χ2=5.000,P=0.172).Conclusion TAF can rapidly inhibit HBV replication and significantly improve liver function in HBV-DC patients,with no significant impact on renal function.However,blood lipid should be closely monitored.

Objective To investigate the basic situation and occupational health conditions of nuclear medicine radiation workers in Jiangsu Province based on the research protocol developed by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences for the nationwide study on the health effects of nuclear medicine radiation in China, understand the impact of occupational radiation on the physical health of nuclear medicine radiation workers, and provide a basis for improving the occupational protection of nuclear medicine radiation workers and reducing the risk of occupational radiation-related health issues. Methods A census approach was used to collect general data and occupational health information of nuclear medicine radiation workers in Jiangsu Province. The analysis focused on the abnormalities in physical examination indicators among radiation workers of different genders, ages, and working years to evaluate the health effects of occupational radiation exposure. Results The occupational health examination data of 472 nuclear medicine radiation workers were collected from 76 medical institutions in Jiangsu Province. The results showed that the detection rate of abnormal hypothyroidism in female workers (8.90%) was higher than that in male workers (2.54%) (P=0.028). With increasing working years, the detection rates of cataract and continuous decrease in white blood cell count increased (P＜0.001). The multivariate logistic regression identified working years as a risk factor for cataract and continuous decrease in white blood cell count (OR=1.59, 95%CI=1.40-3.35, P=0.0003; OR=4.15, 95%CI=3.11-29.91, P=0.0001). In addition, working years was also a risk factor for hypertension, fatty liver, and tumor (OR=2.28, 95%CI=1.51-3.47, P=8.76 × 10⁻⁵; OR=1.69, 95%CI=1.10-2.58, P=0.0145; OR=2.04, 95%CI=1.00-4.16, P=0.0469). Conclusion The study found that working in nuclear medicine could increase the risk of various radiation-related diseases, and the risk is influenced by factors such as working years.

Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

Objective:To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients.Methods:This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis.Results:A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events ( n=58), stroke ( n=24) and cardiac events ( n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events ( HR=1.73, 95% CI 1.17-2.56, P=0.006) and stroke ( HR=2.81, 95% CI 1.53-5.17, P=0.001). Conclusion:Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.

Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

Objective To explore the protective role of DNA damage induced transcription factor 4(DDIT4)in oxidative stress injury in dermal papilla cells and its underlying mechanisms.Methods Dermal papilla cells were exposed to UVA and H2O2 to establish cellular model of oxidative stress.CCK-8 assay was used to detect cell viability under different treatment conditions,and the production of intracellular reactive oxygen species(ROS)was detected using 2',7'-dichlorofluorescein diacetate(DCFH-DA).Autophagic vesicles were observed with electron microscopy.Western blotting was employed to measure the expression of DDIT4 and autophagy-related molecules,including microtubule-associated protein 1 light chain 3(LC3),ubiquitin-binding protein(P62),mammalian target of rapamycin(mTOR),and p-mTOR.Results UVA and H2O2 resulted in more production of ROS(P＜0.05)and decreased viability of dermal papilla cells(P＜0.05).DDIT4 expression was increased in dermal papilla cells under oxidative stress(P＜0.05),and the antioxidant N-acetyl-L-cysteine(NAC)could effectively inhibit this effect(P＜0.05).After treatment with UVA or H2O2,cell autophagy was enhanced in dermal papilla cells,characterized by an increase in the number of autophagosomes and an increased LC3 Ⅱ/Ⅰ ratio(P＜0.05),a decrease in P62 expression(P＜0.05),and 3-methyladenine(3-MA)blocking autophagy led to further reduced cell viability(P＜0.05)and increased intracellular ROS production(P＜0.05).Conversely,rapamycin(RAPA)increased autophagy level and improved the viability of dermal papilla cells under oxidative conditions(P＜0.05),and reduced the generation of intracellular ROS(P＜0.05).Additionally,down-regulation of DDIT4 weakened autophagy in dermal papilla cells under oxidative stress,reduced LC3 Ⅱ/Ⅰ(P＜0.05),increased p-mTOR/mTOR and P62(P＜0.05),inhibited cell viability(P＜0.05),and enhanced intracellular ROS production(P＜0.05).Conclusion DDIT4 may alleviate oxidative stress injury in dermal papilla cells through autophagy.