In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism. METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins. RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention. CONCLUSION The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Hydroxychloroquine/pharmacology* ; Receptors, CXCR4/metabolism* ; Apoptosis/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Chemokine CXCL12/metabolism* ; Interleukin-8/metabolism* ; Interleukin-6/metabolism* ; Receptors, CXCR/metabolism* ; Mesenchymal Stem Cells ; THP-1 Cells

Objective： Varicocele (VC) induces male infertility by mediating changes in the testicular microenvironment, in which testicular hypoxia and high-pressure are important pathological conditions. This study aims to compare the mouse spermatogenesis (GC-2spd) cells and Sertoli (TM4) cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling, and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model. Methods： On the basis of cell hypoxia induced by CoCl2, the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution. After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model, the cells were divided into normal group, hypoxia model group and composite model group. And the levels of OS, programmed cell death, inflammatory factors, and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods. Results： The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L, respectively, and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg (P<0.05). Compared with the normal group, the SOD levels of GC-2 and TM4 cells decreased (all P<0.05), CAT level decreased (all P<0.05), and MDA level increased (all P<0.01), and the OS level of GC-2 and TM4 cells was more obvious than that of the hypoxia model group (all P<0.05). Compared with the normal group, apoptosis occurred in GC-2 and TM4 cells after composite modeling (all P<0.05). Compared with the normal group, the mRNA expressions of IL-1β, IL-18, TNF-α and COX-2 in GC-2 and TM4 cells significantly increased (P<0.01) and higher than those in hypoxia model group (P<0.05) and induced pyroptosis (P<0.01). The expression level of GSDMD increased (P<0.05). Conclusion： The cell model with hypoxia and high pressure combined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone, but also further cause inflammatory response damage and pyroptosis, which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC. This cell model can be used for studying the pathogenesis of VC-associated male infertility, evaluating drug efficacy, and exploring pharmacological mechanisms.
Male ; Animals ; Varicocele/pathology* ; Mice ; Testis/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Hypoxia ; Cobalt ; Sertoli Cells/metabolism* ; Osmotic Pressure ; Spermatogenesis ; Cellular Microenvironment ; Infertility, Male ; Disease Models, Animal

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To observe the effects of matrine on the proliferation,migration,and invasion of human neuroblastoma cells,and to investigate its potential mechanism.Methods This study was divided into AS experimental group(SK-N-AS cells treated with IC50 concentration of matrine),AS blank group(SK-N-AS cells cultured under normal conditions),AS control group(SK-N-AS cells treated with an equal amount of dimethyl sulfoxide),DZ experimental group(SK-N-DZ cells treated with IC50 concentration of matrine),DZ blank group(SK-N-DZ cells cultured under normal conditions),and DZ control group(SK-N-DZ cells treated with an equal amount of dimethyl sulfoxide).Scratch assay and Transwell chamber were used to measure the effect of matrine on the migration and invasion.The expression of E-cadherin,N-cadherin and Vimentin were tested by Western blot.Results After different intervention,the migration percentages of AS blank group,AS control group,AS experimental group,DZ blank group,DZ control group and DZ experimental group were(66.32±3.12)％,(65.27±3.44)％,(23.73±0.79)％,(46.25±4.68)％,(44.15±5.60)％and(16.77±3.52)％,respectively;the number of invasive cells were 870.45±19.32,865.32±23.39,492.74±16.81,1 198.10±43.71,1 203.03±71.91 and 891.69±42.62,respectively;the expression levels of E-cadherin protein were(100.00±11.72)％,(105.65±13.11)％,(477.20±29.71)％,(100.00±12.54)％,(97.78±12.77)％and(240.53±12.23)％,respectively;the expression levels of N-cadherin protein were(100.00±15.44)％,(103.90±10.76)％,(43.52±9.96)％,(100.00±10.12)％,(104.95±10.49)％and(38.39±8.70)％,respectively;Vimentin protein expression levels were(100.00±9.51)％,(97.39±11.33)％,(59.13±10.25)％,(100.00±13.20)％,(96.27±11.01)％and(47.67±9.48)％,respectively.There were statistically significant differences in the above indexes between the AS group and the AS blank group(P＜0.01,P＜0.001),and there were statistically significant differences between the above indexes in the DZ group and the DZ blank group(P＜0.01,P＜0.001).Conclusion Matrine inhibits the proliferation,migration,and invasion of neuroblastoma SK-N-AS and SK-N-DZ cells,potentially through suppressing epithelial-mesenchymal transition.

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.001 2)and the 13-year-old group(P<0.000 1);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.000 1).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.000 1).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.

Objective To construct trajectory models of care-seeking patterns for type 2 diabetes mellitus(T2DM)patients,analyze the influencing factors of different trajectories,and explore the fasting blood glucose control levels of T2DM patients with different trajectories.Methods A retrospective cohort study was carried out on 18088 T2DM patients who had health records and been involved in the diabetic management in Community Health Service Center of Minhang District,Shanghai from 2006 to 2009.Starting from Jan 1,2010,participants were followed up until Dec 31,2019,with complete follow-up information.Group-based trajectory modelling(GBTM)was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients.Bayesian information criterion(BIC),average posterior probability(AvePP)and other evaluation indicators were used to select the optimum subgroup number model.Then the differences in demographic characteristics,health status,family history,fasting blood glucose,BMI,etc were compared among different categories.Multinational logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories.Cox regression analysis was used to examine the relationship between the long-term trajectories of care-seeking patterns and fasting blood glucose control level.Results Using GBTM analysis,we constructed the optimal Model 4 to categorize 18088 T2DM patients with community health records into five distinct trajectory subgroups:continuous non-attendance group(22.29%),low-level increasing group(15.09%),high-level slowly decreasing group(14.18%),high-level rapidly decreasing group(14.90%),and continuous regular attendance group(33.54%).With the continuous regular attendance group serving as the reference,gender,age,place of residence,baseline comorbidity of hypertension,baseline fasting plasma glucose level,and BMI were found to influence the community attendance trajectories of T2DM patients(P<0.05).After adjusting for confounding factors,Cox regression analysis revealed that compared to the continuous non-attendance group,the low-level increasing group,high-level slowly decreasing group,and continuous regular attendance group had better glycemic control,with HRs of 0.37(95%CI:0.34-0.39),0.72(95%CI:0.67-0.78),and 0.78(95%CI:0.73-0.84),respectively.The glycemic control level in the high-level rapidly decreasing group was comparable,with an HR of 1.06(95%CI:0.99-1.12).Conclusion Based on the optimal model,the community medical treatment trajectories of T2DM patients showed different dynamic characteristics.Factors such as gender,residence,hypertension,and weight loss may influence these varying trajectories.Regular community visits and follow-up may help control blood glucose levels.