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.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Objective:This study aims to analyze the trends,hotspots,and interrelations in research on retroperito-neal tumors through bibliometric methods,providing the latest scientific information support for clinicians and research-ers.Methods:Data were sourced from the SCI-expanded database of the Web of Science Core Collection,covering the period from 2004 to 2023.Statistical analysis and visualization of the number of publications,total citations,average citations per article,countries,institutions,journals,and keywords were conducted using Microsoft Excel 2019,VOS-viewer,and CiteSpace.Results:A total of 6,842 relevant articles were retrieved,with a total of 113 753 citations and an average of 16.63 citations per article.The number of publications had been increasing annually,peaking in 2022.The United States,China,and Japan are the major research countries,with the United States contributing the most.Memo-rial Sloan Kettering Cancer Center and the University of Texas MD Anderson Cancer Center are the leading research in-stitutions.The journal with the most publications was the Cureus Journal of Medical Science.Gronchi Alessandro was the most prolific author.The ain keywords were"Management","Surgery",and"Tumor",and the most cited papers focus on surgery and multicenter studies.Conclusion:Research on retroperitoneal tumors is increasing annually,with hot-spots focusing on treatment methods and prognosis analysis.The United States is the main contributor to this field,with significant international collaboration.Future research should further explore the pathogenesis of retroperitoneal tumors and more effective treatment strategies.

Background and Aims:Laparoscopic hiatal hernia repair with mesh reinforcement combined with fundoplication has become the standard surgical approach for treating moderate to severe cases.However,intraoperative and postoperative complications remain a significant concern.This study was conducted to explore the causes of common complications and their prevention and management strategies through retrospectively analyzing clinical data from a single center to optimize perioperative care and improve surgical safety.Methods:The clinical data of 432 patients who underwent laparoscopic hiatal hernia repair with mesh and fundoplication at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to December 2023 were retrospectively analyzed.All procedures were performed by the same surgical team using the standardized seven-step protocol for laparoscopic repair.Postoperative care followed the enhanced recovery after surgery pathway.The incidences of intraoperative and postoperative complications were recorded,and univariate analysis was used to identify risk factors for major postoperative complications.Results:The overall complication rate was 15.3％among 432 patients.The most common intraoperative complication was bleeding(6.9％),primarily from the inferior phrenic vessels(3.2％),short gastric vessels(1.6％),and parenchymal organ injuries(1.9％).The most frequent postoperative complication was dysphagia(12.0％),followed by pneumothorax(3.2％),hernia recurrence(1.9％),mesh infection or erosion(0.7％),gas-bloat syndrome(6.3％),and gastroparesis(0.9％).Most complications were relieved through conservative treatment,endoscopic dilation,or interventional procedures.Two patients with persistent dysphagia underwent reoperation to remove the fundoplication wrap.The median follow-up period was 34 months,with a 6.0％loss to follow-up rate and no perioperative mortality.Univariate analysis showed that patients aged ≥50 years and those who underwent Nissen fundoplication had significantly higher rates of postoperative dysphagia(both P＜0.05).Conclusion:Laparoscopic hiatal hernia repair with mesh and fundoplication is generally safe and effective.However,intraoperative vascular injuries and postoperative dysphagia require special attention.Accurate dissection and identification of anatomical layers are critical during surgery.Surgical strategy should be tailored based on patient age and esophageal motility,with partial fundoplication(Toupet or Dor)preferred when appropriate.Combined with enhanced postoperative recovery protocols,standardized mesh placement and fixation can reduce complication rates and improve long-term outcomes.

Background and Aims:Valeric acid activates the nuclear factor E2-related factor 2(Nrf2)pathway.Recent studies have demonstrated its potent antitumor activity in breast and oral cancers.However,its role in gastric cancer treatment remains unclear.This study aimed to investigate the effects of valeric acid on inflammatory responses and survival in a gastric cancer xenograft model in nude mice and to explore the potential underlying mechanisms to provide new insights for gastric cancer therapy.Methods:A xenograft model was established by subcutaneous injection of human gastric cancer MKN-45 cells into 80 Balb/c nude mice,which were then equally randomized into four groups:control and low-,medium-,and high-dose valeric acid groups(10,20,and 40 mg/kg,respectively).The mice received daily intraperitoneal injections of either saline or valeric acid for 30 days.Tumor growth was monitored during the treatment period.Twelve hours after the final administration,five mice from each group were sacrificed by cervical dislocation;blood was collected via eyeball removal,and tumors were excised and weighed.Histopathological changes in the tumors were observed by HE staining.Serum levels of macrophage inflammatory protein-2(MIP-2),interleukin-10(IL-10),and tumor necrosis factor α(TNF-α)were measured by ELISA.mRNA and protein expression levels of Nrf2 and its downstream molecules,quinone oxidoreductase-1(NQO-1)and heme oxygenase-1(HO-1),were assessed in tumor tissues using qRT-PCR and Western blot.The remaining 15 mice per group were monitored for survival analysis.Results:Compared with the control group,all valeric acid-treated groups showed a significant reduction in tumor volumes at all observation time points and final tumor weight(all P＜0.05),with a dose-dependent trend.HE staining revealed densely arranged tumor cells with high cell density in the control group,while various degrees of tumor necrosis and reduced cell density were observed in valeric acid-treated groups,most pronounced in the high-dose group.ELISA results showed that serum levels of MIP-2 and TNF-α were significantly decreased,while IL-10 levels were significantly increased in valeric acid-treated groups compared to controls(all P＜0.05),exhibiting dose dependence.qRT-PCR and Western blot analyses demonstrated that the mRNA and protein expression levels of Nrf2,HO-1,and NQO-1 in tumors were significantly elevated in the valeric acid groups compared with the control group(all P＜0.05),also showing dose dependence.Survival analysis indicated that the median survival times were 47 d(control),68 d(low dose),81 d(medium dose),and 90 d(high dose),with all valeric acid groups having significantly prolonged survival compared to the control group(all P＜0.05).Conclusion:Valeric acid effectively inhibits the growth of gastric cancer xenografts,attenuates systemic inflammatory responses,and prolongs the survival of nude mice,possibly through activation of the Nrf2 pathway and modulation of the tumor microenvironment.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.