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.

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.

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.

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.

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.

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.

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.

Objective:This study sought to examine the clinicopathological features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and to discuss its differential diagnosis.Methods:A total of 36 MEITL cases, collected between June 2015 and January 2024 from the Fourth Affiliated Hospital of Soochow University and the First Affiliated Hospital, College of Medicine, Zhejiang University, were analyzed. Patients underwent immunohistochemistry, in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER), and T-cell receptor (TCR) gene rearrangement testing. Clinical data, laboratory results, and follow-up information were collected for correlation analysis.Results:The cohort included 36 patients (20 males and 16 females) aged 17-76 years (median: 57 years). Tumors outside the intestine were observed in 22 cases (61%). A total of 32 patients (89%) underwent surgical intervention and/or chemotherapy, and one patient received auto-HSCT. The median follow-up duration was 11.5 months (range: 8-73 months), with a median overall survival of 6 months (range: 1-67 months) ; 34 patients died during the follow-up period. Morphologically, nine cases (25%) exhibited significant pleomorphism. Immunohistochemical analysis revealed that high expression levels of both P53 and c-Myc were correlated with atypical morphology ( P=0.003 and P=0.016, respectively). Notably, patients with high P53 expression had significantly shorter survival times than those with low P53 expression ( χ2=4.922, P=0.027), whereas survival did not differ significantly based on c-Myc expression levels ( χ2=0.034, P=0.854). Furthermore, a PD-L1 CPS score ≥10 was observed in 22 cases (68.8%). Scattered EBER positivity in background cells was identified in four cases. All tested cases (17/17, 100.0%) showed clonal TCR gene rearrangements. Conclusions:MEITL is a rare but highly aggressive lymphoma with distinct clinical and pathological features. A subset of cases may exhibit atypical morphological patterns, complicating the diagnostic process. Improving awareness of this neoplasm is helpful for early and precise diagnosis as well as the estabolishment of novel therapy regimen.