Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

This study was aimed at tracing the molecular typing and drug resistance characteristics of a suspected food poi-soning event caused by Clostridium perfringens in a district of Wuhan City.The FilmArray detection system and multiple fluo-rescence quantitative PCR methods were used to rapidly screen for pathogens in samples from the poisoning event.According to the initial screening results,bacteria were isolated,cultured,and identified by mass spectrometry.Fluorescence PCR was used to detect six virulence genes of the isolated Clostridium perfringens strains.On the basis of whole genome sequencing results,we conducted virulence genes,resistance genes,and whole genome single nucleotide polymorphism genetic evolution(wgSNPs)analyses.Antibiotic sensitivity testing was conducted with the agar dilution method.A total of ten strains of Clos-tridium perfringens were isolated,including eight strains from seven anal swab samples,one strain from fecal samples,and one strain from food samples.Food with suspected contamination had a Clostridium perfringens count of 7.8×106 CFU/g.The PLC(a)toxin gene was detected in all ten gas producing capsule isolation strains,but no other 5 tox-in genes such as CPE were detected,thus confirming that all were type A bacteria producing capsule Clostridium.All strains were 100％resistant to clindamycin and almost completely sensitive to antibiotics such as vancomycin,cefoxitin,and meropenem.Ten strains of Clos-tridium perfringens carried resistance genes such as tetB(P),tetA(P),and mprF,followed by ermQ(70％),ant(6)-Ⅰb(10％),and LnuP(10％).Genetic evolution analysis of wgSNPs indicated that the four outbreak strains clustered together and belonged to an independent subbranch with the suspected food sourcestrains,thus indicating close genetic relationships.In con-clusion,this food poisoning incident might have been be caused by hand torn chickens contaminated with Clostridium perfrin-gens,and the molecular types of the strains revealed high genetic diversity.No multiple drug resistance was observed,but all strains were resistant to clindamycin,an aspect requiring further clinical attention.

OBJECTIVE To investigate the effect and potential mechanism of Ziyin Mingmu Formula in treating age-related mac-ular degeneration(AMD)by combining network pharmacology with animal model validation.METHODS Active ingredients of Ziyin Mingmu Formula were obtained from the TCMSP and BATMAN databases,and their targets were searched using the PharmMapper da-tabase.AMD disease targets were identified using the GeneCards,DrugBank,OMIM,and TTD databases.Venny analysis was per-formed to identify the intersection of active ingredient and disease targets.A protein-protein interaction(PPI)network was constructed using the String database,and core targets were screened using Cytoscape 3.9.0 software.KEGG pathway enrichment analysis was per-formed using the DAVID database.Molecular docking of key active ingredients with core targets was performed using Autodock software.A laser-induced mouse choroidal neovascularization(CNV)model was used.Optical coherence tomography angiography(OCTA)was used to assess CNV area in vivo,immunofluorescence staining was used to assess CNV area on choroidal flat mounts,and Western blot analysis was used to examine the expression of proteins involved in the vascular endothelial growth factor(VEGF)pathway.RESULTS Network pharmacology analysis identified 221 active ingredients in the Ziyin Mingmu Formula.PPI analysis i-dentified 29 core targets,including SRC,protein kinase B(AKT1),mitogen-activated protein kinase 1(MAPK1),and heat shock protein 90α family class A member 1(HSP90AA1).KEGG analysis revealed that the VEGF signaling pathway was the most highly en-riched.Molecular docking revealed that the core targets SRC,AKT1,MAPK1,and HSP90AA1 had good binding affinity with the main active ingredients,diosmetin,catechin,vestitol,and licochalcone A.Animal experiments showed that the Ziyin Mingmu Formula significantly reduced CNV area in model mice,downregulated VEGF protein expression,decreased VEGFR2,p38,and ERK1/2 pro-tein phosphorylation levels,and inhibited the VEGF signaling pathway.CONCLUSION Ziyin Mingmu Formula may inhibit CNV for-mation by regulating the VEGF signaling pathway.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

OBJECTIVE To investigate the effect and potential mechanism of Ziyin Mingmu Formula in treating age-related mac-ular degeneration(AMD)by combining network pharmacology with animal model validation.METHODS Active ingredients of Ziyin Mingmu Formula were obtained from the TCMSP and BATMAN databases,and their targets were searched using the PharmMapper da-tabase.AMD disease targets were identified using the GeneCards,DrugBank,OMIM,and TTD databases.Venny analysis was per-formed to identify the intersection of active ingredient and disease targets.A protein-protein interaction(PPI)network was constructed using the String database,and core targets were screened using Cytoscape 3.9.0 software.KEGG pathway enrichment analysis was per-formed using the DAVID database.Molecular docking of key active ingredients with core targets was performed using Autodock software.A laser-induced mouse choroidal neovascularization(CNV)model was used.Optical coherence tomography angiography(OCTA)was used to assess CNV area in vivo,immunofluorescence staining was used to assess CNV area on choroidal flat mounts,and Western blot analysis was used to examine the expression of proteins involved in the vascular endothelial growth factor(VEGF)pathway.RESULTS Network pharmacology analysis identified 221 active ingredients in the Ziyin Mingmu Formula.PPI analysis i-dentified 29 core targets,including SRC,protein kinase B(AKT1),mitogen-activated protein kinase 1(MAPK1),and heat shock protein 90α family class A member 1(HSP90AA1).KEGG analysis revealed that the VEGF signaling pathway was the most highly en-riched.Molecular docking revealed that the core targets SRC,AKT1,MAPK1,and HSP90AA1 had good binding affinity with the main active ingredients,diosmetin,catechin,vestitol,and licochalcone A.Animal experiments showed that the Ziyin Mingmu Formula significantly reduced CNV area in model mice,downregulated VEGF protein expression,decreased VEGFR2,p38,and ERK1/2 pro-tein phosphorylation levels,and inhibited the VEGF signaling pathway.CONCLUSION Ziyin Mingmu Formula may inhibit CNV for-mation by regulating the VEGF signaling pathway.