Objective:Elucidating causal links between gut microbiota and breast malignancies using mendelian randomization(MR)to Identify specific causal microbial taxa.Methods:Genome-wide association studies(GWAS)summary statistics on gut microbiota and breast malignancies,MiBioGen studied GWAS(N=18473)as exposure samples,and GWAS(N=123579)of breast malignancies in the IEU Open GWAS database as outcome samples.The in-verse variance weighted(IVW),weighted median and MR-Egger methods were used to analyze the MR statistical re-suits.Results:Increased abundance of Pasteurellales increased the risk of breast malignancy(IVW PFDR＜0.05,OR=1.21,95％Cl:1.07～1.36),heterogeneity test and pleiotropy test showed no effect on causality,and the"leave-one-out"method showed that the identified causal association was not driven by any single instrumental variable.The causal relationship is positive.Conclusion:Elevated abundance of pasteurellales in the gut microbiota is associated with an increased risk of breast malignancies

Objective:This study aimed to evaluate the application effect of opioid-free anesthesia(OFA)in modified radical mastectomy for breast cancer.Methods:80 patients undergoing unilateral modified radical mastec-tomy were randomly divided into two groups:general anesthesia group(G group)and OFA group(O group).The G group received general anesthesia with opioid drugs and a laryngeal mask,while the O group received general anes-thesia with intravenous lidocaine combined with thoracic paravertebral nerve block and a laryngeal mask.The average arterial pressure(MAP)and heart rate(HR)of the patients were recorded at the time of admission(T0),induction(T1),start of surgery(T2),gland resection(T3),and admission to the recovery room(T4).The surgical time,awakening time,ex-tubation time,and getting out of bed time were recorded.The VAS score at 2 hours(T5),6 hours(T6),and 12 hours(T7)after surgery,as well as the systemic immune-inflammatory index(SII)before surgery(T8),6 hours after surgery(T9),and 12 hours after surgery(T10)were recorded.The occurrence of postoperative nausea and vomiting(PONV)and post-mastectomy pain syndrome(PMPS)were recorded.The occurrence of adverse events such as poor nerve block effect,pneumothorax,hematoma,and local anesthetic toxicity were also recorded.Results:The MAP and HR of the O group were more stable than those of the G group during surgery(P＜0.05).The awakening time,extubation time,and getting out of bed time in the O group were earlier than those in the G group(P＜0.05).The VAS and SII values after surgery were significantly lower in the O group than in the G group(P＜0.05).The incidence of PONV was also signifi-cantly decreased(P＜0.05).In addition,no adverse events such as pneumothorax,hematoma,or local anesthetic toxic-ity occurred in the O group.Conclusion:Pioid-free anesthesia is safe and effective in modified radical mastectomy for breast cancer,shortening recovery time,time to first flatus,and time to ambulation,while alleviating postoperative pain,systemic inflammatory response,perioperative hemodynamic fluctuations,and the incidence of postoperative nau-sea and vomiting.

Background and Aims:Critical limb ischemia(CLI)represents the end stage of lower extremity arterial disease.Infrapopliteal artery lesions,due to their complex anatomical and pathological characteristics,pose significant therapeutic challenges,with patients facing high rates of amputation and mortality.In recent years,endovascular treatment techniques have evolved rapidly;however,controversy remains regarding the optimal treatment strategy.To systematically compare the efficacy of different treatment modalities,this study conducted a network Meta-analysis to comprehensively evaluate balloon angioplasty(BA),bare-metal stents(BMS),drug-coated balloons(DCB),drug-eluting stents(DES),and orbital atherectomy(OA)in the treatment of CLI involving infrapopliteal artery lesions,providing evidence to guide clinical decision-making on optimal endovascular therapy.Methods:A comprehensive search of multiple medical databases was performed,and 17 randomized controlled trials with a total of 2 379 patients were included.A network Meta-analysis was conducted.The primary outcomes were 1-year primary patency rate,target lesion revascularization(TLR)rate,and major amputation rate.Results:DCB showed the highest efficacy in 1-year primary patency,significantly outperforming DES(OR=4.55,95%CI=1.14-20.00),BMS(OR=15.77,95%CI=3.50-71.00),and BA(OR=9.02,95%CI=2.43-33.47).DCB also demonstrated the lowest 1-year TLR rate,significantly lower than BA(OR=0.40,95%CI=0.22-0.72).There were no statistically significant differences among treatment methods in terms of the 1-year major amputation rate;however,the cumulative ranking analysis suggested that DES may be the most effective in reducing major amputation risk.Conclusion:DCB offers clear advantages in improving primary patency and reducing TLR rates,while DES may be the most effective strategy for reducing the risk of major amputation.DCB and DES should be prioritized in the endovascular treatment of CLI involving infrapopliteal artery lesions.

Background and Aims:Studies have shown that the long non-coding RNA(lncRNA)FGD5-AS1 functions as an oncogene in gastric cancer(GC).Our previous bioinformatics analysis revealed potential binding sites between FGD5-AS1 and microRNA-142-3p(miR-142-3p),as well as between miR-142-3p and pyruvate dehydrogenase kinase 1(PDK1).Therefore,this study aimed to investigate the expression and functional role of the FGD5-AS1/miR-142-3p/PDK1 axis in GC cells.Methods:Dual-luciferase reporter assays were used to verify the targeting relationships between FGD5-AS1 and miR-142-3p,and between miR-142-3p and PDK1.qRT-PCR was conducted to measure the expression levels of FGD5-AS1,miR-142-3p,and PDK1 in GC tissues.A knockdown model of FGD5-AS1(sh-FGD5-AS1)and an miR-142-3p inhibitor were constructed and transfected,alone or in combination,into BGC823 GC cells.Cellular behaviors,including proliferation(CCK8,EdU),apoptosis(flow cytometry),migration,and invasion(Transwell assays),were assessed,along with related protein expression(Western blot).A subcutaneous xenograft model in nude mice was used to evaluate the effect of FGD5-AS1 on tumor growth in vivo.Results:The dual-luciferase assays demonstrated that miR-142-3p mimics significantly reduced the luciferase activity of wild-type(WT)FGD5-AS1 and PDK1 reporters(both P<0.05),but had no effect on mutant(MUT)reporters,confirming a direct binding relationship.Knockdown of FGD5-AS1 led to upregulation of miR-142-3p and downregulation of PDK1 in GC cells,with reduced proliferation,migration,and invasion,and enhanced apoptosis(all P<0.05);these effects were reversed by the miR-142-3p inhibitor.In vivo,FGD5-AS1 knockdown significantly inhibited tumor growth in nude mice and decreased Ki-67 and PDK1 expression in tumor tissues(all P<0.05).Conclusion:FGD5-AS1 may act as a ceRNA that sponges miR-142-3p,thereby relieving its suppression on PDK1,and promoting GC cell proliferation and invasion as well as tumor progression.The FGD5-AS1/miR-142-3p/PDK1 axis plays a critical role in the development of GC and may serve as a potential therapeutic target.

Background and Aims:Gamma-aminobutyric acid(GABA),the principal inhibitory neurotransmitter in the central nervous system,has been increasingly recognized in recent years as being closely associated with various liver-related diseases,such as hepatic encephalopathy,liver cirrhosis,and hepatocellular carcinoma.Abnormal GABA expression is strongly linked to pathological processes including cognitive impairment and neuroinflammation.Although numerous studies have investigated the mechanistic roles of GABA in neurological complications of liver disease,a systematic overview of the field's research trends,collaborative networks,and emerging hotspots remains lacking.This study employs bibliometric methods to comprehensively map the evolution and frontier topics in GABA and liver-related disease research from 2005 to 2024,aiming to inform future research planning and resource allocation in this area.Methods:English-language publications from 2005 to 2024 related to GABA and liver-related diseases were retrieved from the Web of Science Core Collection.Eligible articles were analyzed using VOSviewer,CiteSpace,and the R package"bibliometrix"to visualize and evaluate contributions by countries/regions,institutions,authors,and journals.Additional analyses included keyword clustering,co-citation analysis,and thematic evolution of research topics.Results:A total of 237 articles were included,contributed by 1 340 authors across 456 institutions in 47 countries,and published in 168 journals.The United States and China are leading contributors in this field.Although countries such as the United Kingdom and Italy had fewer publications,they demonstrated higher average citation counts,indicating strong research quality.Notably,Spain's Centro Investigación Principe Felipe and the research team led by Felipo Vicente exhibited high academic influence.Neurochemistry International and Hepatology were identified as core journals,with Hepatology having the highest impact factor(12.9).Keyword clustering revealed major research focuses including the regulatory role of GABA in the neural mechanisms of hepatic encephalopathy,the impact of liver-related metabolic disorders on neurotransmitter balance,the development and evaluation of GABA receptor-targeted therapeutics,and the function of the GABAergic system in the pathogenesis of hepatocellular carcinoma.As research deepens,the frequency of emerging keywords has diversified,with recent emphasis on terms such as"quality of life,""gene expression,"and"fatty liver disease,"reflecting a shift from fundamental mechanisms to clinical translation and interdisciplinary integration.Conclusion:The relationship between GABA and liver diseases has become a focal point of interdisciplinary research.Investigations have expanded from pathological mechanisms to therapeutic applications,with growing interest in GABA's roles in hepatic encephalopathy,metabolic dysregulation,and tumor progression.Future studies should explore the specific functions of GABA receptor subtypes,promote the development of precision-targeted therapies,and investigate novel mechanisms such as the gut microbiota-GABA metabolism-brain-liver axis to broaden the clinical and translational potential of GABA in neurological,metabolic,and oncological contexts.

Background and Aims:Carotid plaque instability is a critical pathological basis for ischemic stroke.Identifying key molecular markers to evaluate plaque stability has important clinical implications.Recent studies have emphasized the regulatory roles and predictive value of long non-coding RNAs(lncRNAs)in plaque stability.In our previous transcriptome sequencing analysis of human stable and unstable carotid plaques,we identified lncRNA C-C motif chemokine ligand 3 antisense RNA 1(CCL3-AS1)as significantly upregulated in unstable plaques,suggesting a potential association with plaque instability.Therefore,this study aimed to validate CCL3-AS1 expression in an expanded plaque sample cohort and to explore its role and underlying molecular mechanism in carotid plaque destabilization.Methods:Carotid plaque specimens were obtained from patients undergoing carotid endarterectomy and classified into stable and unstable groups(n=15 per group)based on HE and Sirius red staining.qRT-PCR was used to validate the expression of candidate lncRNA CCL3-AS1.The localization and co-expression of CCL3-AS1 with macrophages in plaques were determined by RNA fluorescence in situ hybridization(FISH)combined with immunofluorescence staining.In vitro,THP1-derived macrophages were transduced with lentivirus or treated with antisense oligonucleotides(ASO)to overexpress or knock down CCL3-AS1,respectively,and the expression levels of inflammatory cytokines and matrix metalloproteinases(MMPs)were assessed.In vivo,an unstable carotid plaque model was established by tandem ligation of the right carotid artery in apolipoprotein E-deficient(ApoE-/-)mice,followed by local overexpression of CCL3-AS1.The effects on plaque morphology,macrophage infiltration,and MMP-9 expression were evaluated.Additionally,bioinformatic prediction using the catRAPID v2.1 omics platform was performed to identify potential RNA-binding proteins interacting with CCL3-AS1.RNA stability assays and RNA-binding protein immunoprecipitation(RIP)were conducted to verify the regulatory mechanism of MMP-9 expression.Results:CCL3-AS1 was significantly upregulated in unstable carotid plaques and was predominantly localized to the cytoplasm of plaque-infiltrating macrophages.In vitro,overexpression of CCL3-AS1 markedly increased the expression of MCP-1,TNF-α,IL-1β,iNOS,and MMP-9 in macrophages,whereas knockdown had the opposite effect.In the ApoE-/-mouse model of unstable carotid plaques,CCL3-AS1 overexpression led to fibrous cap rupture,increased infiltration of pro-inflammatory macrophages,enhanced MMP-9 secretion,and promoted plaque instability.Co-expression analysis revealed a strong correlation between CCL3-AS1 and MMP-9 expression(r=0.89,P=0.001).RNA stability assays demonstrated that CCL3-AS1 delayed the degradation of MMP-9 mRNA.Bioinformatic prediction identified heterogeneous nuclear ribonucleoprotein K(hnRNP-K)as a potential binding partner of CCL3-AS1.RIP and FISH co-localization confirmed the interaction,suggesting that CCL3-AS1 enhances MMP-9 mRNA stability through binding to hnRNP-K,thereby promoting its expression.Conclusion:As a macrophage-enriched inflammatory lncRNA,CCL3-AS1 may promote carotid plaque instability by enhancing MMP-9 expression via hnRNP-K-mediated mRNA stabilization.This lncRNA represents a potential molecular target for early intervention and stratification of ischemic stroke.

Lower extremity atherosclerotic occlusive disease(ASO)is a common peripheral arterial disease with a steadily increasing global incidence.As a key pathological change in ASO,arterial calcification plays a crucial role in its pathogenesis,diagnostic evaluation,treatment strategies,and prognosis.In recent years,with the continuous advancement of imaging and biomarker detection technologies,quantitative assessment and clinical research on arterial calcification have deepened,providing new perspectives for individualized diagnosis and treatment.This review begins with the pathophysiological mechanisms of arterial calcification and systematically summarizes current detection methods,its impact on endovascular therapy,and recent progress in prognostic evaluation,aiming to provide theoretical support and practical reference for precision treatment of ASO patients.

Mucinous gastric adenocarcinoma(MGC)is a distinct but under-researched subtype of gastric cancer,accounting for approximately 2.2％to 6.8％of all cases.It is characterized by the presence of ≥50％extracellular mucin within the tumor tissue.Although recognized as an independent subtype by international classification standards,significant controversies persist regarding the definition criteria,clinical prognosis,and treatment strategies of MGC.This article systematically reviews the epidemiological features,histological evolution,molecular mechanisms,and imaging characteristics of MGC,with a particular focus on the key issues related to definitional discrepancies,prognostic contradictions,and therapeutic challenges.Addressing these issues may provide references for optimizing clinical diagnosis and treatment,promote the development of individualized therapeutic strategies for MGC,and offer theoretical support for reducing global disparities in gastric cancer management.

The surgical approach for hiatal hernia repair with anti-reflux procedures has transitioned from traditional open thoracotomy to the era of minimally invasive techniques.In recent years,laparoscopic surgery has been widely applied in hiatal hernia repair.Robotic-assisted hiatal hernia repair represents an important trend in the development of minimally invasive surgery for this condition and has seen rapid progress in recent years.However,there is currently no definitive guideline for clinical practice.To further standardize the robotic surgical treatment of hiatal hernia,the Expert Working Group of Gastroesophageal Reflux Disease of Surgeons Society of Chinese Medical Doctor Association,building upon the 2023 consensus,took the lead in organizing domestic experts in related fields to review relevant literature from both China and abroad,discuss key issues and challenges,and formulate the 2024 edition of the expert consensus.This resulted in the publication of the"Chinese expert consensus on robotic-assisted hiatal hernia repair with anti-reflux surgery in adults(2024 Edition)",which aims to provide guidance and reference for the continued advancement of robotic hiatal hernia surgery in China.

Based on the"Laparoscopic standardized seven-step surgical procedure guidelines for hiatal hernia and gastroesophageal reflux disease(GERD)(2021 edition)",this guideline updates the evidence-based evidence from the past four years.It aims to provide standardized and homogenized guidance for the surgical treatment of GERD and hiatal hernia.The guideline elaborates on preoperative examination,surgical indications,contraindications,preoperative preparation,surgical steps,postoperative management,and follow-up.The surgical procedure follows a seven-step approach,which includes placement of trocars,abdominal cavity exploration,mobilization of the abdominal esophagus,closure of the hiatal defect,reinforcement of the diaphragmatic crura with mesh fixation,construction of the anti-reflux valve mechanism,irrigation of the operative field and closure of port sites.The guideline emphasizes the importance of preoperative multidisciplinary evaluation,individualized surgical planning,and management of postoperative complications,aiming to enhance the safety and effectiveness of surgery,reduce postoperative complications,and improve the patient's quality of life.