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.

Medical humanities consistently run through the entire process of medical development and educational reform. However， with the increasingly prominent dominance of evidence-based medicine in clinical practice， the medical humanities have gradually been weakened in both medical education and clinical practice. Narrative medicine， through telling and listening to patients’ stories， enhances healthcare professionals’ empathy， fosters doctor–patient communication， and facilitates a return to the humanistic essence of medical education and clinical practice. By sorting out and reviewing related literature and developmental trends both at home and abroad， this paper pointed out the existing structural problem of an imbalance between technological priority and humanistic care in medical education， focusing on how to achieve an effective integration of medical humanities and narrative medicine in medical education. This paper also systematically analyzed the significance of both medical humanities and narrative medicine in the medical education system and proposed promoting the deep embedding of narrative medicine in medical education from three entry points， namely， curriculum integration， interdisciplinary collaboration， and the construction of teaching evaluation systems. The aim was to provide theoretical support and practical experience for medical education reform， foster the coordinated development of professional competence and humanistic spirit among medical talents， and truly achieve the goal of cultivating well-rounded medical talents.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

ObjectiveTo investigate the impact of hepatocellular carcinoma （HCC） on the prognosis of patients with liver cirrhosis undergoing emergency endoscopic therapy for esophagogastric variceal bleeding， as well as independent influencing factors for the prognosis of liver cirrhosis patients without HCC after emergency endoscopic therapy for esophagogastric variceal bleeding. MethodsA total of 117 liver cirrhosis patients without HCC and 119 liver cirrhosis patients with HCC who underwent emergency endoscopic therapy for esophagogastric variceal bleeding in Renmin Hospital of Wuhan University from January 2017 to July 2023 were enrolled. Basic information including age and sex was collected from all patients， as well as the presence or absence of chronic diseases such as hypertension， diabetes， and coronary heart disease， the time of emergency endoscopy after admission， and liver function parameters including international normalized ratio， albumin， creatinine， sodium， total bilirubin， alanine aminotransferase， and aspartate aminotransferase （AST）. The independent-samples t test was used for comparison of normally distributed continuous variables between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous variables between two groups； the chi-square test was used for comparison of categorical variables between groups. The covariance analysis and the multivariate logistic regression analysis were used for comparison of outcome variables after control of baseline variables， and the Kaplan-Meier survival curve was plotted for each group. The univariate and multivariate Cox regression analyses were performed for survival time in the non-HCC group to investigate the independent influencing factors for survival time， and then the Kaplan-Meier curve analysis and the log-rank test were performed to validate such independent influencing factors and analyze the independent influencing factors for secondary outcomes. ResultsCompared with the non-HCC group， the HCC group had significantly higher red blood cell transfusion units （6.00［2.00～9.00］ vs 4.00［1.75～7.00］， Z=-2.050， P=0.040， F=4.869， adjusted P=0.028）， a significantly shorter survival time （29.77±16.01 days vs 38.07±11.43 days， t=4.574， P<0.001， F=17.294， adjusted P<0.001）， and a significantly higher 5-day rebleeding rate （22.69% vs 6.84%， χ²=11.736， P<0.001， adjusted P=0.021）. The Kaplan-Meier curve analysis showed that the risk of 42-day mortality in the HCC group was 3.897 （95% confidence interval ［CI］： 2.338 ‍— 6.495， P<0.001） times that in the non-HCC group. The multivariate Cox regression analysis of the non-HCC group showed that the total length of hospital stay （hazard ratio ［HR］=0.793， 95%CI： 0.644 ‍— ‍0.976， P=0.029） was an independent protective factor for 42-day survival. The Kaplan-Meier curve analysis showed that a length of hospital stay of >9 days was beneficial for the prognosis of patients （HR=4.302， 95%CI： 1.439 — 12.870， P=0.037）. Blood sodium level （odds ratio ［OR］=0.523， 95%CI： 0.289 ‍— ‍0.945， P=0.032） and MELD-Na score （OR=0.495， 95%CI： 0.257 ‍— ‍0.954， P=0.036） were independent protective factors against 5-day rebleeding， while AST level was an independent risk factor for 5-day rebleeding （OR=1.023， 95%CI： 1.002 ‍— ‍1.043， P=0.028） and in-hospital death （OR=1.036， 95%CI： 1.001‍— ‍1.073， P=0.045）. ConclusionLiver cirrhosis patients with variceal bleeding and HCC tend to have a worse prognosis， and for the non-HCC group， in-hospital mortality rate increases with the increase in AST level. The total length of hospital stay is an independent protective factor for survival time in the non-HCC group， and it is recommended to appropriately prolong the length of hospital stay for such patients.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

ObjectiveTo investigate the prevalence of cardiovascular diseases and their influencing factors in community-based schizophrenia patients in Shanghai, and to provide a scientific basis for the early identification and prevention of cardiovascular disease in this population. MethodsBased on the Shanghai community cohort with severe mental disorders in 2022, a total of 3 954 community-based schizophrenia patients were identified and included in this study through a stratified cluster sampling method. Basic information and relevant clinical data (including metabolic index data) were collected through questionnaire survey, physical examination and laboratory testing. Univariate analyses were performed using the chi-square tests, and multivariate logistic regression analyses were employed to identify influencing factors of comorbid cardiovascular diseases. ResultsA total of 3 954 community-based schizophrenia patients were included, of which a total of 1 237 (31.28%) patients had comorbid cardiovascular diseases. Multivariate logistic regression analyses showed that age 60 years old or above (OR=5.524, 95%CI: 3.716‒8.214), smoking behavior (OR=1.328, 95%CI: 1.042‒1.692), overweight (OR=1.900, 95%CI: 1.046‒3.451) or obesity (OR=2.678, 95%CI: 1.439‒4.985), elevated blood pressure (OR=1.546, 95%CI: 1.294‒1.846), abnormal fasting blood glucose (OR=1.552, 95%CI: 1.322‒1.823) and high-density lipoprotein cholesterol abnormalities (OR=1.283, 95%CI: 1.025‒1.606) were positively associated with the risk of comorbid cardiovascular diseases in patients with schizophrenia, while educational attainment of college/bachelor’s degree or above (OR=0.640, 95%CI: 0.450‒0.910) and being unmarried (OR=0.552, 95%CI: 0.457‒0.667) were negatively associated with the risk of cardiovascular diseases comorbidity. ConclusionAdvanced age, unhealthy behaviors and lifestyles, as well as abnormalities in blood pressure, blood glucose, and blood lipids, could all increase the risk of comorbid cardiovascular diseases in community schizophrenia patients. It is suggested to strengthen the monitoring and management of these risk factors in this population in the future, so as to achieve early detection, early diagnosis and early intervention of cardiovascular diseases.