Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

Objective:To evaluate the immunogenicity and immune persistence of human rabies vaccine (Vero cell) in healthy people aged 10-17 years and compare it with a group of adults aged 18-60 years.Methods:This study was conducted between July 2021 and November 2022 with Shangyu district and Shengzhou city of Shaoxing city, Zhejiang Province selected as the research sites. Zagreb regimen (2-1-1 schedule) and Essen regimen (1-1-1-1-1 schedule) were used for rabies vaccine administration. Serum samples were collected at different time points before and after immunization to compare the differences in seropositivity rates and geometric mean concentrations (GMC) between the 10-17 age group and the 18-60 age group.Results:A total of 1 200 healthy participants aged 10-60 were included, with 157 individuals (13.1%) in the 10-17 age group and 1 043 individuals (86.9%) in the 18-60 age group. Both groups displayed a nearly 100% seropositivity rate at 3, 6 and 12 months, and the participants in the same age group had similar antibody levels. The GMC of antibodies gradually increased after vaccination and peaked on 14 d. The 10-17 age group showed higher GMC of antibodies than the 18-60 age group at 14 d after the first dose (Zagreb regimen: 81.85 IU/ml vs 63.15 IU/ml, t=2.411, P=0.018; Essen regimen: 86.61 IU/ml vs 69.24 IU/ml, t=3.906, P<0.001). Similar differences were observed in the GMC of antibodies at 14 d and 3 months after the full vaccination course, but these differences gradually decreased and disappeared at 6 and 12 months after vaccination. Conclusions:Human rabies vaccine (Vero cell) has lasting immune protection in all participants within one year after vaccination, with no significant differences between the two vaccination regimens. Participants aged 10-17 have higher antibody levels compared to adults aged 18-60, but there is no significant difference in immune persistence between the two age groups.

Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.

Objective:To investigate the prognostic factors of elderly patients with epithelial ovarian cancer(EOC),construct and validate a nomogram prediction model,and provide a basis for clinical diagnosis and treat-ment.Methods:A total of 13128 elderly patients pathologically diagnosed with EOC from 2010 to 2019 in the U.S.SEER database(version 8.4.1)were selected as internal validation data.They were randomly divided in a 7∶3 ratio,with 9138 cases in the training set and 3990 cases in the validation set.All factors were subjected to univari-ate Cox regression analysis;multivariate Cox regression analysis was performed for factors with P＜0.05 to ob-tain their independent prognostic risk factors,and a nomogram model for evaluating 1-,3-,and 5-year overall sur-vival rates was constructed,followed by internal validation.At the same time,the clinical data of 73 elderly EOC patients treated in the First Department of Gynecology at the Affiliated Hospital of Chengde Medical University from January 1,2016 to December 31,2022 were selected for external validation of the nomogram.After construc-ting the nomogram model,by obtaining the risk scores of each independent prognostic factor,the training set,vali-dation set,and external validation set were divided into low-and high-risk groups according to comparison of indi-vidual risk scores and the overall median,the K-M curves for different risk groups were plotted based on the medi-an survival time.Results:①Univariate and multivariate Cox regression analyses showed that,age,marital status,histological type,International Federation of Gynecology and Obstetrics(FIGO)stage,differentiation degree,ser-um tumor carbohydrate antigen 125(CA125)level,unilateral of bilateral tumor,tumor size,positive lymph nodes,residual disease size after cytoreductive surgery,postoperative chemotherapy and surgical treatment were inde-pendent influencing factors for elderly women with EOC(P＜0.05).②According to the drawn column line dia-gram model,the C index values of the training set,the verification set and the external verification set were:0.750,0.732 and 0.798 respectively;the 5-year Area under the curve(AUC)in the Receiver Operating Characteristic(ROC)curve of the external verification set in the three groups was 0.669,while the AUC values for 1-,3-,and 5-year(except the 5-year of external validation)were all greater than 0.700.③Based on the plotted K-M curves,the median survival time of the high-risk groups in the training set,validation set,and external validation set was 31,32 and 39 months respectively,and more than half of the patients in the low-risk group were still alive.The a-bove results all suggested that the column chart model had a high clinical application value for the prediction the 1-,3-,and 5-year overall survival rates of elderly patients with EOC.Conclusions:The nomogram model in this study can accurately evaluate the overall survival rate of elderly with EOC,and provide a basis for individualized treatment.

ObjectiveTo analyze the protective effect of different types of influenza vaccines (InfV) against influenza A among the individuals aged between 3‒17 years old, and to provide a scientific basis for the prevention and control of influenza in the future. MethodsA retrospective cohort study was conducted to collect data on the incidence and InfV vaccination of the individuals aged between 3‒17 years during the influenza epidemic season from 2022 to 2023. Vaccine effectiveness (VE) was calculated, and a log-binomial regression model was used to calculate the corrected VE. ResultsThe incidence rate of influenza in InfV vaccinated and un-vaccinated groups was 7.32% (1 937/ 26 446) and 9.65% (4 421/45 837), respectively. After adjusting for age and gender factors, the unadjusted VE (95%CI) was 54.57% (52.24%‒56.78%). The unadjusted VE (95%CI) was 53.66% (50.36%‒56.74%) for males and 55.60% (52.24%‒58.72%) for females, respectively. The unadjusted VE (95%CI) for the age group of 3‒ years, 6‒ years, 9‒ years, 12‒ years, and 15‒17 years were 64.08% (60.89%‒67.01%), 57.40% (53.71%‒60.80%), 57.77% (52.49%‒62.47%), 24.36% (9.49%‒36.79%), and 24.09% (-17.59%‒51.00%), respectively. The unadjusted VE (95%CI) for quadrivalent split-virion inactivated influenza vaccine, trivalent split-virion inactivated influenza vaccine, trivalent subunit influenza vaccine, and trivalent live attenuated influenza vaccine were 53.84% (51.32%‒56.24%), 62.17% (56.28%‒67.26%), 79.83% (69.94%‒86.46%), and 31.59% (19.07%‒42.18%), respectively. ConclusionThe InfV used during the 2022‒2023 influenza season had a good protective effect against influenza A among the individuals aged between 3‒17 years old, especially in those aged between 3‒11 years old.

Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P＜0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P＜0.05),decreased in SOD activity and GSH content(P＜0.01),and increased in the levels of ROS,LDH,and MDA levels(P＜0.01).In all SA dose,cell apoptosis reduced(P＜0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P＜0.05).In high dose group,the S-phase cells ratio increased(P＜0.05).And in medium/high dose groups,ROS(P＜0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P＜0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P＜0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P＜0.05);and Cytochrome C reduced in all SA groups(P＜0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.

Objective:To understand the current situation of the ability to screen health information of the elderly in rural areas and analyze its influencing factors, so as to provide a basis for taking targeted measures.Methods:A cross-sectional survey was adopted, and rural elderly people in Yonghe Town, Dahu Town and Dayao Town of Liuyang City, Hunan Province were selected as the survey subjects by the convenience sampling method. The investigation was conducted using the general information Questionnaire, the Health Information Discrimination Ability Scale, the filial Piety Expectation Scale and the two-way Social Support Scale.Results:A total of 228 questionnaires were distributed, and 215 valid questionnaires were retrieved, with an effective recovery rate of 94.30%. Among the 215 rural elderly people surveyed, 86 were male and 129 were female. The ability to discriminate health information was (69.19 ± 13.41) points, the expectation of filial piety was (37.67 ± 6.12) points, and the two-way social support was (46.82 ± 8.11) points. The ability of rural elderly people to discriminate health information was positively correlated with filial piety expectations and two-way social support ( r = 0.340, 0.456; both P<0.01). The results of hierarchical regression analysis showed that educational level, filial piety expectations and two-way social support were the influencing factors of the current status of health information discrimination ability of rural elderly people ( t values were 2.60 to 5.35, all P<0.05). Conclusions:The ability of discriminating health information of the elderly in rural areas is affected by the educational level, filial piety expectation and two-way social support. The health information of rural elderly people with low education level should be screened and targeted, so as to enrich their cultural life and combine education with fun. Actively build a filial piety culture to promote children′s attention to their parents. In addition to providing social support for the elderly, we should promote their interpersonal and social communication and exert their self-value, so as to improve the health information screening ability of the elderly in rural areas.

Objective:To investigate the prognostic factors of elderly patients with epithelial ovarian cancer(EOC),construct and validate a nomogram prediction model,and provide a basis for clinical diagnosis and treat-ment.Methods:A total of 13128 elderly patients pathologically diagnosed with EOC from 2010 to 2019 in the U.S.SEER database(version 8.4.1)were selected as internal validation data.They were randomly divided in a 7∶3 ratio,with 9138 cases in the training set and 3990 cases in the validation set.All factors were subjected to univari-ate Cox regression analysis;multivariate Cox regression analysis was performed for factors with P＜0.05 to ob-tain their independent prognostic risk factors,and a nomogram model for evaluating 1-,3-,and 5-year overall sur-vival rates was constructed,followed by internal validation.At the same time,the clinical data of 73 elderly EOC patients treated in the First Department of Gynecology at the Affiliated Hospital of Chengde Medical University from January 1,2016 to December 31,2022 were selected for external validation of the nomogram.After construc-ting the nomogram model,by obtaining the risk scores of each independent prognostic factor,the training set,vali-dation set,and external validation set were divided into low-and high-risk groups according to comparison of indi-vidual risk scores and the overall median,the K-M curves for different risk groups were plotted based on the medi-an survival time.Results:①Univariate and multivariate Cox regression analyses showed that,age,marital status,histological type,International Federation of Gynecology and Obstetrics(FIGO)stage,differentiation degree,ser-um tumor carbohydrate antigen 125(CA125)level,unilateral of bilateral tumor,tumor size,positive lymph nodes,residual disease size after cytoreductive surgery,postoperative chemotherapy and surgical treatment were inde-pendent influencing factors for elderly women with EOC(P＜0.05).②According to the drawn column line dia-gram model,the C index values of the training set,the verification set and the external verification set were:0.750,0.732 and 0.798 respectively;the 5-year Area under the curve(AUC)in the Receiver Operating Characteristic(ROC)curve of the external verification set in the three groups was 0.669,while the AUC values for 1-,3-,and 5-year(except the 5-year of external validation)were all greater than 0.700.③Based on the plotted K-M curves,the median survival time of the high-risk groups in the training set,validation set,and external validation set was 31,32 and 39 months respectively,and more than half of the patients in the low-risk group were still alive.The a-bove results all suggested that the column chart model had a high clinical application value for the prediction the 1-,3-,and 5-year overall survival rates of elderly patients with EOC.Conclusions:The nomogram model in this study can accurately evaluate the overall survival rate of elderly with EOC,and provide a basis for individualized treatment.

Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P＜0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P＜0.05),decreased in SOD activity and GSH content(P＜0.01),and increased in the levels of ROS,LDH,and MDA levels(P＜0.01).In all SA dose,cell apoptosis reduced(P＜0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P＜0.05).In high dose group,the S-phase cells ratio increased(P＜0.05).And in medium/high dose groups,ROS(P＜0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P＜0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P＜0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P＜0.05);and Cytochrome C reduced in all SA groups(P＜0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.