Objective To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics. Methods The intracellular metabolites of C. albicans intervened by different drugs including NAM, AmB, and their combination with a proper concentration were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database. Results Compared with the control group, the NAM intervention group was hardly separated from it, while the AmB group and NAM+AmB group showed a clear trend of separation. Under the intervention of AmB, 23 metabolites significantly changed compared with the control group, and 28 metabolites remarkably changed after NAM+AmB intervention, including amino acids, organic acids, sugars and other components. Conclusion NAM, as an endogenous metabolite of C. albicans, combined with AmB could enhance the effects of AmB in the original metabolic pathway and changed it to a certain extent. It was speculated that AmB combined with NAM may pose more antifungal effect on Candida albicans by regulating the tricarboxylic acid cycle，interfering with amino acid metabolism and influencing polyamine synthesis.

ObjectiveTo analyze the epidemiological and etiological characteristics of hand-foot-and-mouth disease (HFMD) in Jinjiang District of Chengdu City from 2014 to 2024, and to provide a reference basis for HFMD prevention and control. MethodsA retrospective study was conducted to collect confirmed and clinically diagnosed cases of HFMD in Jinjiang District from January 1, 2014 to December 31, 2024. Descriptive epidemiological methods were used to analyze the distribution of cases by person, time, and place. Joinpoint regression models were applied to examine trends for incidence and severe case rates, while seasonal patterns were analyzed using the seasonal index method. Chi-square tests were used for comparing rates, Mann-Whitney U tests were applied for comparing two groups with skewed distributions, and Kruskal-Wallis H rank-sum tests were used for multiple groups with skewed distributions. Pathogen characteristics were primarily analyzed using descriptive statistics. ResultsA total of 15 561 HFMD cases were reported from 2014 to 2024. The annual crude incidence rate ranged from 51.32/100 000 to 502.50/100 000, the age-standardized incidence rate ranged from 55.56/100 000 to 721.07/100 000, peaking in 2018, and the overall epidemic intensity generally showed an alternating-year pattern of intensification. A total of 85 severe cases were reported, showing a declining trend in the severe case rate (APC=AAPC=-37.57%, 95%CI∶ -51.49%‒21.33%， P<0.01). Severe cases were most common in the 1‑year‑old age group (43.53%), with a median age of 1.88 years. Recurrent infections accounted for 1 245 cases (8.00%), with 96.73% of these being reinfections. The median age at first infection for recurrent cases was 1.98 years, significantly lower than that of single-infection cases (2.69 years, P<0.001), and the median interval between consecutive infections was 1.19 years. The disease exhibited a bimodal seasonal pattern, with epidemic peaks occurring from May to July and from October to December, however, summer peaks extending into autumn were observed in 2018 and 2023. There were statistically significant differences in age distribution across different years (H=467.51, P<0.001), with the median age increasing from 2.25 years in 2018 to 4.18 years in 2024, and the interquartile range widening from 1.84 to 3.78 years. Since its initial detection in 2017, CVA6 has been identified annually, showing a peak proportion of 87.50% in 2023 and a second peak of 68.18% in 2018. CVA10 was detected during 2021‒2023, peaking at 18.75% in 2021 and decreasing to 14.29% in 2022. Male incidence rates were consistently higher than female rates each year (P<0.05). The proportion of males in the reinfection group was significantly higher than that in the single-infection group (χ²=9.951, P=0.002). Pathogen analyses showed that CVA16 was detected annually, EV71 detection declined fluctuantly and was not detected after 2022. CVA6 was first detected in 2017 and rapidly increased in prevalence, reaching 87.50% in 2023 and becoming the dominant strain. Among severe cases, EV71 accounted for the highest proportion (52.63%), while CVA16 was most common in non-severe cases (41.60%). There was a statistically significant difference in pathogen composition between severe and non-severe cases (χ²=10.402,P=0.011). ConclusionThe epidemiological profile of HFMD undergoes continuous changes over time. It is necessary to strengthen routine surveillance, with particular attention to changes in the pathogen spectrum and age distribution, so as to provide evidence for precise prevention and control measures and the adjustment of vaccination strategies.

With the increase in the obese population and the aging of the society,the incidence rates of type 2 diabetes mellitus(T2DM)and obstructive sleep apnea(OSA)continue to increase,and more than half of the patients with T2DM also suffer from OSA.T2DM patients with OSA have a higher risk of developing macrovascular and microvascular complications,which severely impairs their quality of life,and early identification of T2DM patients with OSA can improve their prognosis.This article summarizes the latest re-search advances in the pathogenesis,biomarkers,and treatment measures of T2DM with OSA,in order to provide insights for the screening,diagnosis,and treatment of T2DM with OSA.

Objective Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA)guidelines,to obtain precise and reliable comprehensive effect conclusions by quantitatively combining pharmacodynamic results from animal experiments investigating Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for treatment of acute pancreatitis(AP)in literature reports through meta-analysis.Methods Databases including China National Knowledge Infrastructure(CNKI),VIP Database for Chinese Technical Periodicals(VIP),Wanfang Data Knowledge Service Platform,China Biomedical Literature Database(CBMdisc),PubMed,and Web of Science(WOS)were searched from inception to March 2025 for animal studies related to Astragali Radix(single-entity Astragali Radix preparation)or its ingredients for AP treatment.Risk of bias for included studies was assessed with SYRCLE tool.Heterogeneity among studies was evaluated according to Cochrane Handbook using Cochrane's Qtest and/2statistic.Sensitivity analysis was performed using the leave-one-out method,and publication bias risk was detected using Egger's test.Results A total of 297 articles were retrieved,and after screening and evaluation,19 animal studies were finally included for meta-analysis.These 19 publications cover SD rats,as well as three breeds of mice:C57BL/6 mice,BALB/c mice,and Kunming mice.SYRCLE scores ranged from 3 to 4.The results of the sensitivity analysis showed that no study significantly affected the heterogeneity index.The results of Egger's test showed a significant publication bias with P＜0.05.Cochrane's Qtest and I2statistic indicated substantial heterogeneity among studies.Meta-analysis results of 19 animal studies showed that single-entity Astragali Radix preparation(Astragali Radix injection)could reduce serum amylase(AMY)levels,an AP-specific indicator.The Astragali Radix ingredients could decrease both AMY and lipase(LPS)levels.Astragali Radix injection or its ingredients could reduce serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β,while increasing IL-10 levels;could increase serum levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and decrease malondialdehyde(MDA)levels.High-dose groups of Astragali Radix injection or Astragali Radix ingredients were more effective than low-dose groups in reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels,but dosage effect on MDA levels was not demonstrated.Conclusion Evidence-based analysis of animal experiment results shows that in various animal models including SD rats,C57BL/6 mice,BALB/c mice,and Kunming mice,Astragali Radix injection or its ingredients can effectively reduce expression or secretion levels of AP-specific indicators(AMY and LPS).The mechanisms may be related to some inflammatory mediators,including reducing TNF-α,IL-6,and IL-1 β levels and increasing IL-10 levels;They may also intervene in oxidative/antioxidative equilibrium,such as increasing SOD and GSH-Px levels and reducing MDA levels.Except for MDA,dose-response relationships are shown for reducing AMY,TNF-α,and IL-6 levels and increasing SOD levels with Astragali Radix injection or its ingredients.However,due to high heterogeneity,potential publication bias risk,and species differences between animal models and human diseases in existing studies,further high-quality clinical trials or animal experiments are still needed in the future.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Objective To explore the efficacy and underlying mechanism of Astragalus in the treatment of viral pancreatitis using network pharmacology,with confirmation of its efficacy and mechanism in cell experiments.Methods Astragalus and viral pancreatitis targets obtained from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)and GeneCards databases were combined to obtain intersection targets.GO functional enrichment and KEGG signaling pathway enrichment analyses of therapeutic targets were conducted using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)database.The interactions between therapeutic targets were analyzed using the STRING database and Cytoscape 3.10.2,and the core therapeutic targets were screened.Molecular docking between the most effective therapeutic components and the core targets was performed using PyMOL 3.0 and AutoDock Tools 1.5.7.CVB3 was used to construct a viral pancreatitis cell model for verification of the core targets.Results Seventy-eight therapeutic targets were identified.Enrichment analyses revealed the possible involvement of pathways related to cancer,lipids and atherosclerosis,and PI3K-AKT signaling.AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9 were identified as possible core targets.The result of cell experiments showed that the expression level of AMY was significantly increased in the model group(P＜0.05).The Astragalus injection group exhibited significantly decreased expression levels of AMY,AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9 compared with the model group(P＜0.05).Conclusions Astragalus injection effectively treated viral pancreatitis,and its therapeutic mechanism may involve reduced expression levels of AKT1,TP53,HIF1A,CASP3,IL-6,and MMP9.