Chronic cerebral hypoperfusion (CCH) plays an important role in the occurrence and development of vascular dementia (VD). Recent studies have indicated that multiple stages of immune-inflammatory response are involved in the process of cerebral ischemia, drawing increasing attention to immune therapies for cerebral ischemia. This study aims to identify potential immune therapeutic targets for CCH using bioinformatics methods from an immunological perspective. We identified a total of 823 differentially expressed genes associated with CCH, and further screened for 9 core immune-related genes, namely RASGRP1, FGF12, SEMA7A, PAK6, EDN3, BPHL, FCGRT, HSPA1B and MLNR. Gene enrichment analysis showed that core genes were mainly involved in biological functions such as cell growth, neural projection extension, and mesenchymal stem cell migration. Biological signaling pathway analysis indicated that core genes were mainly involved in the regulation of T cell receptor, Ras and MAPK signaling pathways. Through LASSO regression, we identified RASGRP1 and BPHL as key immune-related core genes. Additionally, by integrating differential miRNAs and the miRwalk database, we identified miR-216b-5p as a key immune-related miRNA that regulates RASGRP1. In summary, the predicted miR-216b-5p/ RASGRP1 signaling pathway plays a significant role in immune regulation during CCH, which may provide new targets for immune therapy in CCH.
Humans ; Computational Biology/methods* ; Brain Ischemia/therapy* ; Immunotherapy ; MicroRNAs/genetics* ; Signal Transduction ; Dementia, Vascular/genetics* ; Chronic Disease

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) Zihua Wenfei Zhisou Granule (ZWZG) in postinfectious cough (PIC) patients with CM syndrome of wind-cold invading Fei (Lung, WCIF). METHODS: This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase II clinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory Departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A (ZWZG-matched placebo 15 g), group B (active ZWZG 15 g), and group C (active ZWZG 10 g plus ZWZG-matched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score (CSS), cough Visual Analog Scale (VAS) value, Cough-Specific Quality of Life Questionnaire (CQLQ) score, and CM syndrome score from baseline (day 0) to post-treatment (day 14). Adverse events (AEs) in each group were recorded. RESULTS: A total of 198 patients were included in the full analysis set (FAS) and safety analysis set (SS), while 183 were enrolled in the per-protocol analysis set (PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85% in groups A, B, and C, respectively; while the cough disappearance rate was 31.34%, 72.31% and 68.18%, respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A (P<0.0001). Both the median time to cough relief and cough disappearance in groups B and C were shorter than group A (P<0.0001). Compared with group A, groups B and C showed significantly greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS (P<0.05). There were no significant differences in changes from baseline to post-treatment in CQLQ and CM syndrome scores among 3 groups (P>0.05). Results in the PPS population were consistent with those in the FAS population. Groups B and C showed lower incidence in AEs than group A (P<0.05), while there was no significant difference between groups B and C (P>0.05). No drug-related severe AEs were reported. CONCLUSIONS ZWZG can increase cough disappearance rate and cough relief rate; and it is beneficial in shortening cough duration and reducing cough severity and frequency in patients suffering from PIC. It is safe and generally well tolerated. (Registration No. ChiCTR1900022078).
Humans ; Cough/drug therapy* ; Double-Blind Method ; Male ; Female ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Treatment Outcome ; Adult ; Aged ; Quality of Life

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Objective To investigate the effects of acetylshikonin on proliferation,invasion and migration of oxaliplatin-resistant human colon cancer HCT116 cells(HCT116/L-OHP).Methods HCT116/L-OHP cells were divided into blank group,control group,experimental-L group,experimental-M group and experimental-H group.The control group was treated with 10 μmol·L-1 oxaliplatin.The experimental-L,experimental-M,experimental-H groups were treated with 1.25,2.50 and 5.00 μmol·L-1 acetylshikin and 10 μmol·L-1 oxaliplatin,respectively.The blank group was given routine culture.The changes of HCT116/L-OHP cell proliferation were detected by cell counting kit-8(CCK-8)method;flow cytometry was used to evaluate the apoptosis of cells;Transwell assay was used to detect the changes of cell migration and invasion ability;Western blot was used to detect the expressions of P-glycoprotein(P-gp),matrix metallo-proteinases 2(MMP2),nuclear factor kappa-B(NF-κB)/and hypoxia induced factor-1 α(HIF-1α)proteins.Results The cell inhibition rates of the blank group,control group and experimental-L,-M,-H groups were 0,(8.27±0.01)％,(10.53±0.02)％,(34.17±0.01)％and(48.47±0.05)％;cell apoptosis rates were(0.13±0.02)％,(1.37±1.04)％,(9.73±0.87)％,(26.71±4.26)％and(40.75±4.70)％;invading cells were 130.70±9.81,127.10±9.21,71.83±3.57,28.83±1.87 and 19.63±6.11;the number of migration cells was 150.50±10.17,148.40±8.13,94.58±4.09,63.98±5.09 and 31.85±5.50;the relative expression levels of P-gp protein were 0.91±0.01,0.89±0.02,0.75±0.04,0.61±0.07 and 0.25±0.03;the relative expression levels of MMP2 protein were 1.24±0.01,1.22±0.02,0.96±0.01,0.53±0.01 and 0.16±0.02;the relative expression levels of NF-κB-p65 were 1.12±0.12,1.07±0.01,0.78±0.01,0.64±0.02 and 0.31±0.03;the relative expression levels of HIF-1 α were 0.65±0.04,0.52±0.03,0.41±0.02,0.35±0.03 and 0.09±0.01,respectively.The above indicators in the experimental-L,-M,-H groups showed statistically significant differences compared to those of blank group(all P＜0.05).Conclusion Acetylshikonin combined with oxaliplatin can significantly inhibit the proliferation,invasion and migration of HCT116/L-OHP cells,and induce cell apoptosis,which may be related to the inhibition of P-gp and MMP2 expression and the activation of NF-κB/HIF-1 α signal.

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.