ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

OBJECTIVE To systematically evaluate the risk factors for ineffective eradication therapy of adult Helicobacter pylori （Hp） infection. METHODS Retrieved from PubMed，Web of Science， the Cochrane Library， Embase， CNKI， VIP and Wanfang Data， cohort studies and case-control studies on the eradication therapy for Hp infection in adult patients were searched from Jan. 2000 to Jul. 2024. After screening literature， extracting data， and evaluating the quality of literature， RevMan 5.3 software was used for meta-analysis， and sensitivity analysis and publication bias analysis were also performed. RESULTS A total of 19 articles were included， all of which were cohort studies， involving 9 931 patients in total. Among them， 1 929 patients were ineffective in eradication therapy， with the ineffective rates ranging from 8.02% to 33.33%. Meta-analysis showed that age＜50 years [OR＝1.33， 95%CI （1.12，1.57）， P＜0.001]， body mass index （BMI）＞25 kg/m2 [OR＝1.87， 95%CI （1.35， 2.59）， P＝ 0.000 2]， a history of smoking [OR＝1.62， 95%CI（1.35， 1.95）， P＜0.001]， a history of drinking [OR＝1.93， 95%CI（1.47， 2.54）， P＜0.001]， living in a rural area [OR＝1.74， 95%CI（1.41， 2.15）， P＜0.001]， having non-peptic ulcer [OR＝3.45， 95%CI （1.75， 6.67）， P＝0.000 3]， a family members’ infection history [OR＝4.72， 95%CI（3.32， 6.74）， P＜0.001]， poor treatment compliance [OR＝4.89， 95%CI （3.07， 7.79）， P＜0.001]， amoxicillin resistance [OR＝3.42， 95%CI （1.95， 6.00）， P＜0.001] and clarithromycin resistance [OR＝8.14， 95%CI（5.00， 13.24）， P＜0.001] had significant impacts on ineffective eradication therapy of Hp infection in adults. Sensitivity analysis and publication bias analysis showed that the result of this study was robust and reliable. CONCLUSIONS Age＜50 years， BMI＞25 kg/m， a history of smoking， a history of drinking， living in a rural area， having non-peptic ulcer， a family members’ infection history， poor treatment compliance， amoxicillin resistance and clarithromycin resistance are risk factors for failure of Hp infection eradication therapy in adults.

Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering characteristics of scarlet fever in Jinhua City, Zhejiang Province from 2005 to 2023, so as to provide a reference for improving the prevention and control strategy of scarlet fever. Methods: The data of scarlet fever cases in Jinhua City from 2005 to 2023 were collected from the China Information System for Disease Control and Prevention, and descriptive epidemiological method was used to analyze the epidemiological characteristics of scarlet fever. The average annual percent change (AAPC) was calculated to analyze the trend of scarlet fever incidence from 2005 to 2023. The spatial-temporal clustering of scarlet fever was identified using spatial autocorrelation analysis and space-time scanning analysis. Results: A total of 1 494 scarlet fever cases were reported in Jinhua City from 2005 to 2023, and the average annual reported incidence rate was 1.41/100 000, with no significant change trend (AAPC=1.706%, P>0.05). There were two incidence peaks, from April to June and from November to January of the next year. There were 937 males and 557 females, with a male to female ratio of 1.68∶1. The age was mainly <10 years (1 391 cases, 93.11%), of which 3-<7 years was the high incidence age group (936 cases, 62.65%). There were 1 466 cases of preschool children, students, and scattered children, accounting for 98.13%. The average annual reported incidence of scarlet fever in Dongyang City, Pujiang County, and Yongkang City was 4.58/100 000, 3.04/100 000, and 1.99/100 000, respectively. The spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of scarlet fever in Jinhua City from 2005 to 2023 (Moran's I=0.579, P<0.05), and the high-high clustering areas were mainly distributed in Dongyang City and Pujiang County. The spatial-temporal scanning analysis showed that there were 8 spatial-temporal clustering areas of scarlet fever in Jinhua City from 2005 to 2023. The class Ⅰ clustering area was 9 towns in Dongyang City, and the clustering period was from August 2013 to December 2022. There were 7 class Ⅱ clusters, covering some streets in Pujiang County, Dongyang City, Yongkang City, Yiwu City, and Pan'an County. Conclusions From 2005 to 2023, the incidence of scarlet fever in Jinhua City was relatively low, and children aged 3-<7 years had a high incidence, and there was a spatiotemporal clustering. The peak incidence was from April to June and from November to January of the next year. Dongyang City, Pujiang County, and Yongkang City had high incidence areas.

Objective: To analyze the epidemiological characteristics of leptospirosis in Jinhua City, Zhejiang Province, from 2007 to 2024, so as to provide a basis for improving the prevention and control strategies of leptospirosis. Methods: Data pertaining to leptospirosis cases in Jinhua City from 2007 to 2024 were collected through the Monitoring and Reporting Management System of the Chinese Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the distribution characteristics of leptospirosis in terms of time, region, population, interval from the onset of the disease to diagnosis and the outbreak of the epidemic. Results: A total of 81 cases of leptospirosis were reported in Jinhua City from 2007 to 2024, with an average annual reported incidence of 0.08/100 000. The peak incidence occurred from August to September, with 57 cases accounting for 70.37%. Leptospirosis cases were reported in 9 counties (cities, districts) in Jinhua City. Pan'an County reported the most cases, with 52 cases accounting for 64.20%. There were 54 male cases and 27 female cases, with a male-to-female ratio of 2∶1. The majority of cases were aged over 40 years, with 73 cases accounting for 90.12%. The average reported incidence of leptospirosis showed an upward trend with the increase of age (P<0.05), and the highest incidence of leptospirosis was at the 60-<80 age group (0.21/100 000). The majority of patients were farmers, with 77 cases accounting for 95.06%. The median interval from onset to diagnosis was 4.00 (interquartile range, 6.00) days. There were significant differences in the interval from onset to diagnosis among cases in Dongyang City compared with Pan'an County, Wuyi County, and Wucheng District, between Pan'an County and Jindong District, Wucheng District, and between Wuyi County and Wucheng District (all P<0.05). In 2007, one outbreak of leptospirosis was reported, which occurred in Jiuhe Township, Pan'an County, with 36 reported cases. Conclusions The reported incidence of leptospirosis in Jinhua City from 2007 to 2024 is generally low. The high-incidence period is from August to September, and Pan'an County is the high-incidence area. Males over 40 years and farmers are the key populations for prevention and control. It is recommended to strengthen epidemic surveillance and health education for high-risk populations.

The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans ; Point-of-Care Testing ; Critical Care ; Blood Coagulation Tests/methods* ; Male ; Blood Coagulation ; Female ; Middle Aged ; Reproducibility of Results ; Prothrombin Time ; Aged ; Adult ; Point-of-Care Systems

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective To analyze the detection situation and variation tendency of volatile components of organic solvents in enterprises in Longgang District, Shenzhen City. Methods A total of 368 enterprises using organic solvents in Longgang District, Shenzhen City from 2019 to 2022 were selected as the research subjects using judgment sampling method. And its 2 086 reports of occupational hazards monitoring on volatile components of organic solvents in workplaces from 2019 to 2022 were collected for analysis. Results Among the 2 086 organic solvent samples, the top 10 chemical substances in terms of detection rates were toluene, methanol, xylene, n-hexane, ethylbenzene, dimethoxymethane, dichloromethane, acetone, ethyl acetate and cyclohexane, with detection rates ranging from 16.73% to 29.72%. The detection rate of benzene in organic solvent samples from 368 enterprises decreased from 13.84% to 5.13% from 2019 to 2022 (P<0.01). The detection rate of trichlorethylene decreased from 3.58% to 0.45% (P<0.01), and the detection rate of dichloroethane decreased from 4.53% to 1.81% (P<0.01). However, the reduction in the detection rate of n-hexane was not significant (from 28.88% to 23.08%, P>0.05). Benzene had relatively high detection rates in yellow glue, super glue, and thinner (10.94%, 10.00%, and 8.45%, respectively). The detection rate of n-hexane was relatively high in super glue, cleaning agent and car wash liquids (90.00%, 61.84%, and 46.81%, respectively). The detection rate of trichlorethylene was relatively high in cleaning agent (3.95%), and the detection rate of dichloroethane was relatively high in super glue (40.00%). Conclusion From 2019 to 2022, the detection rates of traditional occupational hazards such as benzene, trichloroethylene, and dichloroethane in the volatile organic components used in Longgang District enterprises showed a downward trend.