ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Background and aims Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide, with no currently effective treatment. ALD is caused by excessive lipid buildup, which eventually triggers inflammation and fibrosis in the liver. Activation of hepatic Kupffer cells (KCs) and macrophages drives liver inflammation, which can worsen alcohol-induced liver injury. The autophagy-lysosome system is crucial for macrophages to support their innate immune functions. Transcription factor EB (TFEB) is a key regulator of autophagy and lysosomal biogenesis, but the role of macrophage TFEB in ALD development is unknown. The aim of this study was to evaluate the effects of Gao-binge alcohol consumption on myeloid cell TFEB and elucidate the role of myeloid TFEB in ALD. Methods Two-to-three-month-old male and female LysM Cre− (WT) and LysM Cre+ Tfeb Flox/Flox (f/f) (myeloid-Tfeb KO) mice were subjected to chronic alcohol feeding plus an acute binge following the Gao-binge model. Serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol content were determined using biochemical assays. Total hepatic protein content and messenger RNA (mRNA) levels of autophagy-related proteins and inflammatory markers were determined using immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). Isolated hepatic infiltrating macrophages and KCs from mice given intragastric ethanol infusions were analyzed by Western blot for TFEB and autophagy-related protein content. Raw 264.7 macrophages were treated with ethanol, lipopolysaccharide (LPS), and LPS plus ethanol to examine nuclear TFEB translocation using immunofluorescence. Results We found that TFEB levels were higher in macrophage/KC cells than in hepatocytes and cholangiocytes. While ethanol feeding increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as hepatic triglyceride levels, no significant differences were observed between WT and myeloid-Tfeb KO mice. The number of F4/80-positive KCs/macrophages was similar in all four experimental groups, but hepatic neutrophil infiltration increased in alcohol-fed myeloid-Tfeb KO mice. LPS or ethanol alone induced nuclear TFEB translocation only moderately in Raw 264.7 macrophages. Conclusions Our findings suggest that myeloid TFEB is dispensable for alcohol-induced liver injury in mice.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

There is a complex biological mechanism in the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which plays a key role in the development and development of lymphoma.In this review,the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed,and found that the research and development,application,efficacy,and adverse reactions of PI3K inhibitors are the current research hotspots,and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma.In order to maximize the clinical benefits,a variety of strategies need to be explored,including novel drugs with better selectivity and safety,and related combination therapies.

Objective:To explore the clinical characteristics and prognosis risk factors of aggressive NK-cell leukemia(ANKL).Methods:The clinical and laboratory data of 34 patients with ANKL and 15 patients with chronic lymphoproliferative disorders of NK cells(CLPD-NK)admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2024 were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,and the Cox proportional hazards regression model was used to analyze prognostic factors.Results:Compared with CLPD-NK patients,ANKL patients had a younger median age of onset,a higher proportion patients with EBV-DNA≥500 copies/ml,hepatosplenomegaly and hemophagocytic syndrome.They also presented with a higher peak of fever,a shorter median survival time,lower WBC count,PLT count,ALB and Fib values,while having higher LDH,AST,TG,ferritin,CRP and PCT levels.There were statistically significant differences in the morphology and expression of HLA-DR,CD56,CD57,CD16 and CD158 on abnormall cells between ANKL patients and CLPD-NK patients.Multivariate survival analysis revealed that combined with asparaginase treatment could improve patients' survival,and CRP≥ 15 mg/L and Fib＜2.0 g/L were independent risk factors affecting the overall survival of patients with ANKL.Conclusion:The differences in clinical features and laboratory tests between patients with ANKL and CLPD-NK aid in the diagnosis of ANKL.CRP and Fib levels can be used to predict the prognosis of patients,and combined asparaginase therapy can enhance the overall survival of patients.

Sheep and goats are important tuberculosis hosts found predominantly in plateau and mountainous regions.In recent years,the number of reported tuberculosis cases in sheep and goats has increased.The tuberculosis pathogen can spread among vari-ous animal species and even infect humans,thus further complicating disease prevention and control,and posing a serious threat to the health of both humans and livestock.This article summarizes the global prevalence of tuberculosis in sheep and goats,and specifi-cally analyzes the epidemic status in China.Frequently used tuberculosis detection methods in sheep and goats are described,and the shortcomings of each method are briefly introduced.Additionally,on the basis of frequently applied methods for monitoring,handling,and controlling tuberculosis in sheep and goats worldwide,suggestions are offered to provide a reference for tuberculosis control in sheep and goats in China.

mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

Objective:To investigate the iodine nutrition status of children aged 8 to 10 in Hefei City, Anhui Province, and to provide a theoretical basis for scientific supplementation of iodine for children.Methods:Using multi-stage stratified cluster random sampling method, from 2020 to 2023, in 9 counties (cities and districts) of Hefei City, each counties (cities and districts) were divided into 5 sampling areas according to east, west, south, north and center each year, with one township (street) selected from each area, and one primary school was selected from each township (street), forty non-boarding students aged 8 to 10 years old (half male and half female, with balanced age distribution) were selected from each primary school. Household edible salt samples and one random urine sample were collected for iodine level testing. B-ultrasound method was used to examine the thyroid of children and goiter rate was calculated.Results:A total of 7 200 children's household edible salt were tested, the salt iodine level [ M( Q1, Q3)] was 22.6 (20.6, 24.5) mg/kg, the coverage rate of iodized salt was 98.0% (7 057/7 200), the qualified rate of iodized salt was 96.1% (6 784/7 057), and the qualified iodized salt consumption rate was 94.2% (6 784/7 200). The qualified iodized salt consumption rate was 87.7% (1 578/1 800) in 2023, which did not meet the standard for eliminating iodine deficiency disorders. A total of 7 200 urine samples were tested, the urinary iodine level was 236.0 (161.0, 327.0) μg/L. There were statistically significant differences in the urinary iodine levels among children from different years ( H = 57.96, P < 0.001), ages ( H = 10.01, P = 0.007), and gender ( Z = - 9.01, P < 0.001). A total of 7 200 children were tested for goiter, of which 135 had goiter, with a goiter rate of 1.9%. Conclusions:From 2020 to 2023, the iodine nutrition of children aged 8 - 10 years in Hefei City is generally at an appropriate level. The urinary iodine and goiter rate of children have reached the standard for eliminating iodine deficiency disorders, but the qualified iodized salt consumption rate has not reached the standard for eliminating iodine deficiency disorders, which should be highly valued.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.