BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

OBJECTIVE To compare the efficacy and safety of different daily doses of aspirin in the prevention of preeclampsia （PE）. METHODS The case-control studies and prospective randomized controlled trials on aspirin with daily dose ≥ 100 mg （trial group） vs. ＜100 mg （control group） in the prevention of PE were retrieved from PubMed， Medline， Embase， the Cochrane Library， CNKI， China Biomedical Literatue Database and Wanfang Data from base-building to January 2025. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 literatures were included， involving 3 052 pregnant women. Meta-analysis showed the incidence of PE [RR＝0.63， 95%CI （0.53，0.76）， P＜0.000 01]， gestational hypertension [RR＝0.69， 95%CI （0.50，0.94），P＝0.02]， preterm birth [RR＝0.56， 95%CI （0.47，0.66）， P＜0.000 01]， and intrauterine growth retardation [RR＝0.73，95%CI （0.61，0.87），P＝0.000 5] in trial groups were significantly lower than control group. The incidence of postpartum hemorrhage between the two groups had no statistically significant difference [RR＝1.17， 95%CI （0.90，1.53），P＝0.25]. Subgroup analysis showed that the incidence of PE in Chinese pregnant women taking 150 mg of aspirin was significantly higher than taking 100 mg of aspirin [RR＝3.40， 95%CI （1.29， 8.93）， P＝0.01]； but there was no significant difference between the two groups in the incidences of postpartum hemorrhage， preterm birth （P＞0.05）. CONCLUSIONS Aspirin with daily dose ≥100 mg is more effective in preventing PE than daily dose ＜100 mg， with lower rates of gestational hypertension， preterm birth， and intrauterine growth retardation. It does not increase the risk of postpartum hemorrhage. For pregnant women in China， daily dose 100 mg of aspirin may be more effective in preventing PE than 150 mg.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

Objective To investigate the status of self-management ability in elderly patients with type 2 diabetes mellitus(T2DM)in community,and to analyze the influencing factors using structural equation model.Methods A convenient sampling method was used to investigate patients aged 65 years and above with T2DM in Hongkou district of Shanghai.The patients were assessed using diabetes self-management questionnaire(DSMQ),Beck depression inventory(BDI),diabetes management self-efficacy scale(DMSES),and diabetes distress scale(DDS).Spearman correlation analysis was conducted to explore the relationship among the variables.A structural equation model was constructed to analyze the effect of depression,self-efficacy,and diabetes distress on self-management levels among the patients.Results A total of 588 elderly patients with T2DM were included in this survey,the DSMQ score was 32.00(28.00,38.00),the DMSES score was 158.50(135.25,172.00),the BDI score was 0.00(0.00,2.00),and the DDS score was 23.00(18.00,31.00).The final model demonstrated good fit to the sample data,self-efficacy had a positive impact on self-management levels(β=0.558,P＜0.001),and depression had a positive impact on diabetes distress(β=0.599,P＜0.001).Conversely,depression had a negative impact on self-efficacy(β=-0.314,P＜0.001),and diabetes distress also had a negative impact on self-efficacy(β=-0.267,P＜0.001).Self-efficacy had the greatest impact on self-management level(the total effect was 0.558),and it was a direct impact.Depression(the total effect was-0.264)and diabetes distress(the total effect was-0.149)had indirect effects.Self-efficacy played a mediating role between depression and self-management,with an indirect effect of-0.175,accounting for 66.3%of the total effect.Self-efficacy and diabetes distress played a chain mediating role between depression and self-management,with an indirect effect of-0.089,accounting for 33.7%of the total effect.Conclusion Self-efficacy has the greatest effect on the self-management level of elderly patients with diabetes mellitus.Depression and diabetes distress indirectly affect self-management levels through the mediating role of self-efficacy.Community and clinical healthcare workers should focus on enhancing the self-efficacy of patients with diabetes mellitus and implementing targeted interventions for their symptoms of depression and diabetes distress,so as to improve their self-management capabilities.

Objective To explore the mediating role of mobile phone dependency and self-rated health in the relationship between adverse childhood experiences(ACEs)and mental health among young adults.Methods A cross-sectional study was conducted using cluster random sampling among 1 611 young adults(mean age 26.30 years)from a region in Hainan Province.Participants completed the childhood trauma questionnaire(short form),the mobile phone addiction index,the depression-anxiety-stress scale(simplified Chinese version),and a self-rated health questionnaire.Pearson correlation analysis and mediation effect analysis were employed to examine the relationships among ACEs,mobile phone dependency,self-rated health,and mental health.Results ACEs,mobile phone dependency,and self-rated health were all significantly correlated with mental health(all P＜0.01).ACEs had a direct negative effect on mental health(direct effect=0.221,95%confidence interval[CI]0.150-0.293).Furthermore,ACEs exerted indirect effects on mental health through 3 pathways:the independent mediation of mobile phone dependency(indirect effect=0.081,95%CI 0.035-0.130),the independent mediation of self-rated health(indirect effect=0.034,95%CI 0.011-0.062),and the chain mediation of mobile phone dependency and self-rated health(indirect effect=0.009,95%CI 0.004-0.015).Conclusion ACEs have a significant impact on the mental health of young adults,with mobile phone dependency and self-rated health serving as key mediators.Interventions aimed at reducing mobile phone dependency and improving health status may help mitigate the negative impact of childhood trauma on mental health,thereby promoting psychological well-being in this population.

Objective To investigate the association between antenatal white blood cell count(WBC)and the risk of histological chorioamnionitis(HCA)in pregnant women with late pregnancy premature rupture of membranes(PROM).Methods A retrospective analysis was performed on totally 118 pregnant women with PROM in late pregnancy from March 2018 to August 2021 in the hospital.They were divided into HCA group and non-HCA group according to the presence or absence of HCA.The general clinical data,laboratory indica-tors and delivery outcomes of the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the association between prenatal WBC and HCA risk.Generalized additive models were used for curve fitting,and segmented regression models were used to further explain the nonlinear relationship between maternal prenatal WBC and HCA risk.Results The prenatal WBC of the HCA group was signifi-cantly higher than that of the non-HCA group(P＜0.001).After adjusting for covariates,elevated prenatal WBC increased the risk of HCA,with an OR of 1.190(95％CI:1.006-1.406,P=0.042).Curve fitting showed that there was a nonlinear relationship between prenatal WBC and HCA risk,and the log-likelihood ratio test of WBC at the inflection point 13.5×109/L(95％CI:11.75-14.56)was statistically significant(P=0.029).For the three groups of prenatal WBC,the risk of HCA in pregnant women gradually increased with the increase of WBC level,which was 0.314(95％CI:0.200-0.456)in the normal group,0.439(95％CI:0.252-0.645)in the high group,and 0.682(95％CI:0.354-0.893)in the elevated group.Conclusion The higher the prenatal WBC of pregnant women with PROM in late pregnancy,the greater the risk of HCA,but there is no simple linear relationship between the two,and there is a threshold effect.