Driven by the growing practical need to accelerate drug development and the continuous innovation of trial design in recent years， the number of protocol amendments during clinical trials have gradually increased， and the changed contents have become more flexible and complex， which significantly heightens the difficulty of ethical review on amendments. Against this backdrop， it is of great importance to fully leverage the role and responsibilities of ethics committees， effectively control clinical trial risks， and ensure subject safety. This paper analyzed development trends of protocol amendments in recent years， sorted out requirements for protocol amendments in Chinese regulations and guiding principles， and examined difficulties of amendment ethical review in practical work. Based on these， targeted strategies and recommendations were proposed， namely， strengthening the integration with scientific review， enhancing the formal review， adjusting the scope of review according to approval notifications， and adopting appropriate review methods， with a view to providing insights and references for the management of the amendment ethical review in drug clinical trials.

Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Objective To explore the feasibility and safety of non-anticoagulation veno-venous extracorporeal membrane oxygenation(VV-ECMO)in patients with severe chest trauma.Methods A retrospective cohort study method was used.A total of 19 patients with severe chest trauma who received VV-ECMO with a delayed anticoagulation strategy at Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to October 2021 were included in the delayed anticoagulation group,and 20 patients with severe chest trauma who received VV-ECMO with a non-anticoagulation strategy from November 2021 to October 2024 were included in the non-anticoagulation group.The overall clinical characteristics of the patients were statistically analyzed,including gender,age,injury severity score(ISS),acute physiology and chronic health evaluationⅡ(APACHEⅡ),reason for VV-ECMO,use of vasoactive drugs,oxygenation index(PaO2/FiO2),and interval from injury to VV-ECMO.The primary outcomes were hemorrhagic and thrombotic complications.The secondary outcomes were blood transfusion during VV-ECMO,VV-ECMO time,mechanical ventilation time,intensive care unit(ICU)length of stay,and 28-day mortality.Results There was no significant difference in gender,age,ISS score,APACHEⅡscore,reason for VV-ECMO,use of vasoactive drugs,PaO2/FiO2,and interval from injury to VV-ECMO between the non-anticoagulation group and the delayed anticoagulation group.There was no significant difference in overall incidence of hemorrhagic and thrombotic between the two groups[incidence of hemorrhagic complications:15.0%(3/20)vs.31.6%(6/19),incidence of thrombotic:15.0%(3/20)vs.5.3%(1/19),both P>0.05].The infusion rate of 4 or more paked red blood cell(PRBC)within 24 hours during VV-ECMO in the non-anticoagulation group was significantly lower than that in the delayed anticoagulation group[5.0%(1/20)vs.31.6%(6/19),P<0.05].The amount of PRBC and platelet transfusion and the time on VV-ECMO in the non-anticoagulation group during VV-ECMO were significantly lower than those in the delayed anticoagulation group[PRBC(U):5.8±3.8 vs.8.1±3.1,platelets(U):1(0,1)vs.2(1,3),time on VV-ECMO(hours):71.55±24.37 vs.114.21±34.08,all P<0.05].There were no statistically significant differences in the amount of plasma and cryoprecipitate transfusion during VV-ECMO,mechanical ventilation time,ICU hospitalization time,and 28-day mortality between the two groups.Conclusion For patients with severe chest trauma receiving VV-ECMO withholding routine systemic anticoagulation did not result in thrombotic complications or higher mortality and required less PRBC and platelet transfusions.Non-anticoagulant VV-ECMO is safe and feasible for patients with severe chest trauma with high risk of bleeding.

OBJECTIVE To explore the molecular characteristics of small colony variants(SCVs)of Staphylococcus aureus isolates so as to provide theoretical bases for clinical control of the persistent and recurrent infections in-duced by the SCVs.METHODS The clinical blood specimens that were collected from the First Affiliated Hospital of Traditional Chinese Medicine University of Guangzhou were cultured to acquire 1 strain of SCV S.aureus S2.The colonial morphology,growth rate,catalase,plasma-coagulase,production capability of biofilm and antimi-crobial susceptibility of the strain SCVs were observed,the growth curve and autolysis curve were drawn,the whole genome sequencing was performed for the S2,the phylogenetic evolution of the genome and the single nu-cleotide polymorphism(SNP)were analyzed.RESULTS The S2 was identified as S.aureus,with the catalase and plasma-coagulase tested positive.The strain was resistant to various types of antibiotics,including macrolides like erythromycin and azithromycin,fluroquinolones such as levofloxacin and ciprofloxacin,and penicillin.The forma-tion of pigment was reduced,the formation of hemolytic rings was low;the growth rate of the strain was slower than that of ATCC 25923(quality control strain)and ZC1(the normal control strain),the autolytic activity of the strain was higher than that of the ATCC 25923 and ZC1,and the biofilm production of the strain was remarkably less than that of the ATCC 29213(P＜0.05).The whole genome sequencing demonstrated that the molecular typ-ing of the S2 was ST239-t030 clone,which harbored a variety of drug resistance genes and virulence genes,and the menB gene had missense mutation.CONCLUSION The formation of SCVs may be associated with the inhibited synthesis of menadione caused by the missense mutation of menB gene.

OBJECTIVE To analyze the epidemiological characteristics of hospital-associated infections(HAIs)in a large scale three-A hospital and assess the occurrence and development trends of HAIs before and after COVID-19 epidemic and during different stages of prevention and control strategies so as to provide scientific bases for HAIs management.METHODS The surveillance data were collected from the patients who were hospitalized in a large scale three-A hospital by nosocomial infection real-time surveillance system from Jan.2018 to Dec.2023.The prevalence trend,infection sites and distribution of pathogens were analyzed.The study period was divided into the pre-epidemic stage and the epidemic stage,the epidemic stage was divided into the strict infection prevention and control phase and the loose infection prevention and control phase.The epidemiological characteristics of HAIs were observed and compared.RESULTS From 2018 to 2023,the prevalence rate of HAIs was decreased from 3.39％to 2.21％,and there was significant difference in the prevalence rate of the infections among the years(x2=105.00,P＜0.001).During the six years,the prevalence rate of HAIs was highest in the internal medicine wards of critical care medicine department(54.91％),and the gram-negative bacteria(56.61％)were dominant among the pathogens.Lower respiratory tract(41.85％),bloodstream(20.93％)and urinary tract(20.50％)ranked the top 3 infection sites;the lower respiratory tract infection ranked the first place before the COVID-19 epidemic and the different stages of epidemic.The overall prevalence rate of HAIs was 3.26％during the epidemic period,remarkably lower than 3.91％before the COVID-19 epidemic(P＜0.001);the overall prevalence rate of HAIs was 2.21％in the loose prevention and control phase of 2023,remarkably lower than 3.78％in the strict prevention and control phase(P＜0.001).CONCLUSIONS The prevalence of HAIs generally shows a downward trend during the six years.The lower respiratory tract is the major infection site,and the gram-negative bacteria are dominant among the pathogens,especially Klebsiella pneumoniae.The prevention and control strategies for the COVID-19 epidemic may facilitate the reduction of incidence of HAIs,and the prevalence rate is remarkably reduced even in the loose prevention and control phase.It is necessary for the hospital to take targeted prevention and control measures based on the departments,carry out rigid surveillance of the major infection sites and patho-gens,and conduct multidisciplinary coordinated prevention and control so as to control the HAIs.

Objective:To investigate the expression of lysosome-associated membrane protein 3(LAMP3)and activating transcription factor 4(ATF4)in cervical cancer and their correlation with clinicopathological parameters.Methods:The expression of LAMP3 and ATF4 in normal cervical tissues,cervical intraepithelial lesions,and cervical cancer tissues was detected by SP immunohistochemistry.The relationships between the expression of these two proteins and patient clinicopathological parameters were analyzed,as well as the correlation between LAMP3 and ATF4 expression.Results:LAMP3 was negative or lowly expressed in both normal cervix tissues and high-grade squamous intraepithelial lesions,but highly expressed in cervical cancer tissues(38.3%),showing a statistically significant difference(χ2=14.113,P=0.001).ATF4 was highly expressed in 26.7%of the normal cervix tissues,10.0%of the high-grade squamous intraepithelial lesions,and 58.3%in the cervical cancer tissues,also showing a significant difference(χ2=11.078,P=0.004).In cervical cancer,LAMP3 expression was significantly associated with FIGO stage(χ2=10.139,P=0.006)and lymph node metastasis(χ2=8.475,P=0.004);ATF4 expression was significantly associated with tumor size(χ2=4.578,P=0.032),FIGO stage(χ2=8.971,P=0.009),and lymph node metastasis(χ2=7.881,P=0.005).There was a positive correlation between the expression of LAMP3 and ATF4 in cervical cancer tissues(r=0.388,P=0.002).Conclusion:LAMP3 and ATF4 are highly expressed in cervical cancer tissues and are positively correlated.Both of them play important roles in the development and progression of cervical cancer and could serve as potential therapeutic targets for cervical cancer treatment.

Objective:To investigate the association between high-risk human papillomavirus (hrHPV) persistent infection and vaginal microecology.Methods:A total of 53 women were enrolled in the gynecological clinic of Beijing Obstetrics and Gynecology Hospital from January 2020 to January 2021, including 7 women without HPV and 46 women with hrHPV infection. Among the hrHPV infected women, 24 woemn who did not use any drugs were classified as the observation group and the other 22 women who were given standardized interferon vaginal administration for 3 months were regarded as the treatment group. Vaginal secretions of all women were taken for Gram-stained microecological test at the time of enrollment and at the 4, 8, and 12 month follow-up. HPV turning negative was taken as the end point of follow-up.Results:(1) Women of hrHPV persistent infection in the observation and treatmnet groups had more times of abortions ( P=0.180). (2) The hrHPV negative conversion rate was 17% (4/24) in the observation group and 36% (8/22) in the treatment group, but the difference was not significant ( P=0.183). The median hrHPV negative conversion time were 11.0 months and 7.5 months in the observation and treatment groups, respectively, and the difference was statistically significant ( P=0.001). (3) Vaginal microecology was generally normal at the time of enrollment and at the end of follow-up in women with HPV natural negative conversion in the observation group. While vaginal microecological disorders were more common in women with hrHPV persistent infection in the observation and treatmnet groups, including high vaginal pH value, poor vaginal cleanliness, poor grade of Lactobacillus and increased vaginal clutter bacteria, and the vaginal microecological situation did not improve after the 12-month follow-up. (4) In the treatment group, women who turned HPV negative within six months all had normal vaginal microecology when enrollment (5/5). While those who turned negative six months later had a higher proportion of vaginal clutter bacteria (2/3), a poor grade of Lactobacillus (2/3) and a higher proportion of vaginal dysbiosis (2/3). Conclusions:(1) Interferon therapy could shorten the negative turning time of hrHPV. (2) Women with normal vaginal microecology have the ability to naturally clear hrHPV. (3) The vaginal microecological Gram-stain test has limited value in predicting hrHPV clearance, perhaps due to its inability to detect Lactobacillus subtypes.

Objective:To establish a rat model of vulvovaginal candidiasis (VVC) and to directly observe the histopathological and ultrastructural characteristics of vaginal mucosal barrier after Candida albicans infection and treatment with Lactobacillus crispatus.Methods:Female unmated SD rats were used to establish the VVC model and divided into three groups (normal group, VVC group, and Lactobacillus group; n=6 per group). Lactobacillus group received intravaginal administration of Lactobacillus crispatus suspension, while rats in VVC group and normal group were infused with phosphate buffered solution instead. Vaginal tissues were collected on day 4 post-treatment for HE staining and transmission electron microscopy (to observe ultrastructural pathological changes). Results:The results of HE staining revealed the disruption and desquamation of vaginal epithelium, necrotic epithelial tissues, neutrophil infiltration in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal structure (mucosal layers and thickness) to normal levels, mucosal layers of Lactobacillus group and normal group were 9.50±1.38 vs 10.67±1.03 ( P=0.226), mucosal thickness of Lactobacillus group and normal group were (116.50±12.14) vs (130.33±13.91) μm ( P=0.211). The results of transmission electron microscopy revealed intercellular desmosome rupture, loss of microvilli and glycocalyx on superficial cells, and mitochondrial swelling in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal ultrastructures (mitochondria and intercellular connections, etc.) to normal levels. Conclusions:Fungal infection severely disrupte the vaginal mucosal barrier in rats. Lactobacillus crispatus could restore the vaginal mucosal barrier and epithelial ultrastructures.