Retinopathy of prematurity(ROP)is a leading cause of childhood blindness, with extremely preterm and very-low-birth-weight infants now constituting the main high-risk group. ROP progresses in two stages: early retinal microvascular degeneration and progressive vascular arrest, followed by abnormal neovascularization in the avascular area. Early oxidative and nitrosative stress—amplified by oxygen fluctuations and immature antioxidant defenses—drives the two-phase pathogenesis via hypoxia-inducible factor/vascular endothelial growth factor(HIF/VEGF), NOX/STAT3, and nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE)pathways, mediating apoptosis of endothelial cells, damage to barrier and pathological angiogenesis. This review systematically analyzes different oxygen-induced retinopathy(OIR)models, elucidates key signaling pathways including Notch, Wnt in physiological and pathological vascularization, with particular emphasis on the biphasic effects of Nrf2 and the differential roles of NOX signaling between phases. We also discuss the limitations of anti-VEGF therapy and oxygen management principles. Reactive oxygen species(ROS)play context-dependent roles across vaso-obliteration and neovascularization phases. Based on mechanistic insights, we propose future directions including combined/sequential interventions, ferroptosis and lipid peroxidation targeting, nano-delivery systems for enhanced bioavailability, and perinatal safety assessment strategies, aiming to provide translatable mechanistic basis for reducing pathological neovascularization while promoting physiological vascular development.

Objective: To investigate the association between childhood obesity and type 2 diabetes mellitus (T2DM) as well as coronary artery heart disease (CHD). Methods: Genome-wide association study (GWAS) data for childhood obesity were collected from the ECG consortium, encompassing information on children aged 2 to 18 years, including 18 613 cases and 12 696 controls. GWAS data for T2DM were collected from the DIAGRAM consortium, including 242 283 cases and 1 569 734 controls. GWAS data for CHD were collected from the CARDIoGRAMplusC4D consortium, including 10 801 cases and 137 371 controls. Pleiotropic genes associated with both T2DM and CHD were analyzed using the MAGMA, PLACO and conditional false discovery rate (cFDR) methods. Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) method, exploring the causal relationships among childhood obesity, T2DM and CHD. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. The mediating variables among the three diseases were investigated by using a mediation analysis. Results: The results of MAGMA, PLACO and cFDR analyses identified 80 pleiotropic genes associated with both T2DM and CHD, primarily distributed on chromosomes 3, 17 and 19. The MR analysis revealed that childhood obesity increased the risk of T2DM (OR=1.151, 95%CI: 1.033-1.283) and CHD (OR=1.158, 95%CI: 1.068-1.255), T2DM increased the risk of CHD (OR=1.182, 95%CI: 1.139-1.227), and CHD increased the risk of T2DM (OR=1.124, 95%CI: 1.055-1.198). The MR-Egger regression analysis showed no horizontal pleiotropy, and the MR-PRESSO test did not identify any outliers (all P>0.05). Mediation analysis indicated that childhood obesity directly increased the risk of CHD (effect value=0.096, 95%CI: 0.012-0.180) and indirectly increased the risk of CHD through T2DM (effect value=0.023, 95%CI: 0.005-0.041), with the mediation effect accounting for 15.65% of the total effect. Conclusions There are potential causal associations between childhood obesity and T2DM as well as CHD, with a bidirectional causal relationship between T2DM and CHD. T2DM also plays a mediating role in the association between childhood obesity and CHD.

Objective: To investigate the epidemiological characteristics of hepatitis E in Shaoxing City, Zhejiang Province from 2006 to 2024, so as to provide the evidence for the prevention and control of hepatitis E. Methods: Data on hepatitis E incidence in Shaoxing City from 2006 to 2024 were collected through the Surveillance System of China Information System for Disease Control and Prevention. The epidemiological characteristics were analyzed using descriptive epidemiological methods. The trend in hepatitis E incidence was analyzed using the average annual percent change (AAPC) and annual percent change (APC). The spatial-temporal clustering characteristics of hepatitis E incidence were identified using spatial-temporal scanning analysis. Results: A total of 2 408 hepatitis E cases were reported in Shaoxing City from 2006 to 2024, with an average annual reported incidence of 2.55/100 000. The overall trend was not statistically significant (AAPC=3.181%, P>0.05). Specifically, it showed an upward trend from 2006 to 2011 (APC=17.371%, P<0.05), a downward trend from 2011 to 2019 (APC=-12.497%, P<0.05), and an upward trend from 2019 to 2024 (APC=18.076%, P<0.05). The epidemic season of hepatitis E was from January to May, with seasonal indices of 122.09%, 118.60%, 145.02%, 129.57%, and 106.15%, respectively. The top three average annual reported incidences were identified in Zhuji City, Xinchang County, and Shengzhou City, with rates of 4.18/100 000, 2.85/100 000, and 2.74/100 000, respectively. The average annual reported incidence of hepatitis E was higher in males than in females (3.52/100 000 vs. 1.56/100 000, P<0.05). A relatively large number of hepatitis E cases were reported among individuals aged 40-<70 years, with 1 639 cases (68.06%). Among them, the group aged 60-<70 years had the highest average annual reported incidence of hepatitis E, at 4.92/100 000. Farmers constituted the predominant occupational group, accounting for 1 515 cases (62.92%). Spatial-temporal scanning analysis identified two clusters in Shaoxing City from 2006 to 2024. The class Ⅰ cluster was located in Shengzhou City, with aggregation time from January 1, 2011 to May 1, 2014. The class Ⅱ cluster was located in Xinchang County, with aggregation time from December 1, 2012 to March 31, 2013. Conclusions The reported incidence of hepatitis E in Shaoxing City from 2006 to 2024 exhibited a pattern of an initial increase, followed by a decrease, and then a subsequent rise. The disease demonstrated higher prevalence during the winter and spring seasons. Key populations for targeted control and prevention include males, individuals aged 40-<70 years, and farmers. Shengzhou City and Xinchang County were identified as high-risk areas.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective: To prepare an inactivated hepatitis A vaccine using a attenuated strain of hepatitis A virus (HAV) H2 and to analyze its immunizing dose, so as to provide the reference for development and production of inactivated hepatitis A vaccines. Methods: Human embryonic lung diploid cells (KMB17) were infected with attenuated HAV H2 strain to proliferate the virus, then the cells containing viruses were harvested, extracted and purified. The obtained virus concentrate was prepared into vaccine bulk and test vaccines with 1 280 EU/mL antigen content. Vaccine testing was carried out according to the inactivated hepatitis A vaccine standards specified in the Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). A total of 110 mice were randomly divided into 11 groups, including 5 dose groups (80, 160, 320, 640 and 1 280 EU/dose) of the test vaccine and the reference vaccine, as well as the adjuvant control group. Mice were immunized twice by intraperitoneal injection, their serum HAV antibodies were detected, and the geometric mean titer (GMT) and positive conversion rate of antibodies were analyzed to evaluate the immunising dose of the vaccine. Results: The antigen content and viral titer of the virus harvest solution were 5 120 EU/mL and 8.33 lgCCID50/mL, respectively. The removal rate of foreign protein reached 98.05% and the recovery rate of antigen was 66.25%. The test vaccine met the requirements of Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). The GMTs of HAV antibodies in the test vaccine and the reference vaccine dose groups after the second immunization were more than twice higher than those after the first immunization. Regardless of primary immunization or secondary immunization, the GMTs (log2) of HAV antibodies in the test vaccine groups with doses of 160 EU/dose and above were higher than those in the 80 EU/dose group (all P<0.05), while there was no statistically significant differences between the dose groups of 160 EU/dose and above (all P>0.05). The antibody positive conversion rate of 160 EU/dose and above of the test vaccine was 100.00% after the secondary immunization. Conclusions The inactivated hepatitis A vaccine of attenuated H2 strain tested in this study demonstrates strong immunogenicity in mice, suggesting its potential as a candidate vaccine. The preliminary analysis indicates an immunizing dose of 320 EU/dose for children and 640 EU/dose for adults.

Secondary caries is one of the main reasons that affect the service life of the restoration. Compared with primary caries, secondary caries have some particularities in etiology, disease progression, clinical manifestation, clinical diagnosis, treatment and prevention. Starting from the above aspects, combined with the latest basic and clinical research on secondary caries, this paper summarizes and analyzes its pathogenesis and prevention strategies, which will lay a certain foundation for in-depth understanding of secondary caries and promoting its clinical prevention and treatment.

Objective:To explore the mediating role of mentoring function between proactive personality and transition shock in new nurses, with the aim of providing reference and basis for managers to develop effective intervention measures for new nurses during their transformational period.Methods:Convenience sampling method was used to select 280 new nurses from the Second Affiliated Hospital of Zhejiang University School of Medicine, and a cross-sectional survey was conducted by applying the General Information Questionnaire, Transition Shock Scale, Proactive Personality Scale, and Mentoring Function Scale. The mediating role of mentoring function between new nurses′ proactive personality and transition shock was evaluated by constructing structural equation modelling.Results:265 valid questionnaires were ultimately collected. Among 265 nurses, there were 25 males and 240 females, with an age of (22.88 ± 2.12) years. The score of transition shock, proactive personality, and mentoring function of new nurses were (83.45 ± 18.95), (58.66 ± 9.96) and (81.72 ± 14.46) respectively; transition shock was negatively correlated with proactive personality and mentoring function ( r=-0.379, -0.340, both P<0.01), and proactive personality was positively correlated with mentoring function ( r=0.452, P<0.01); the mediating effect of mentoring function between proactive personality and transition shock was significant (95% CI -0.085 - -0.015, P<0.01), accounting for 29.14% of the total effect. Conclusions:New nurses' transition shock is at a moderately high level, and proactive personality can affect transition shock directly or indirectly through mentoring function. Managers can mitigate new nurses′ transition shock by improving the quality of mentoring.