ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To analyze the clinical efficacy of laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope.Methods:The clinical data of 96 patients with cholecystolithiasis and choledocholithiasis who were admitted to the Department of Hepatobiliary Surgery, the Third Hospital of Nanchang from September 2021 to November 2024 were retrospectively analyzed. There were 49 male and 47 female patients, aged (59.2±13.9) years. The 96 patients were randomly divided into two groups according to the surgical methods: the flexible ureteroscope group ( n=48) and the choledochotomy group ( n=48), patients who underwent laparoscopic cholecystectomy plus flexible ureteroscope for common bile duct exploration and stone removal via the cystic duct were included in the flexible ureteroscope group; patients who underwent laparoscopic cholecystectomy plus choledocholithotomy and T-tube drainage placement were included in the choledochotomy group. Clinical data including operation time, intraoperative blood loss, postoperative intestinal function recovery time, abdominal drainage tube removal time, postoperative hospital stay and postoperative complications were compared between the two groups. Results:Compared with the choledochotomy group, the operation time [150 (120, 176) min vs. 197 (165, 240) min], intraoperative blood loss [20 (10, 30) ml vs. 30 (20, 50) ml], postoperative intestinal function recovery time [2 (1, 2) d vs. 3 (2, 4) d], abdominal drainage tube removal time [6 (4, 7) d vs. 7 (6, 8) d], and postoperative hospital stay [8 (6, 9) d vs. 16 (13, 17) d] in the flexible ureteroscope group were all reduced, and the differences were statistically significant (all P<0.05). The incidence of postoperative complications in the choledochotomy group was 10.4% (5/48), compared with 2.1% (1/48) in the flexible ureteroscope group. There was no statistically significant difference ( χ2=1.60, P=0.206). Conclusion:Compared with laparoscopic choledocholithotomy plus T-tube drainage, laparoscopic common bile duct exploration and stone removal via the cystic duct with a flexible ureteroscope can shorten the hospital stay of patients with choledocholithiasis, offering a minimally invasive, safe and effective treatment method.

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.