THE non-public economy has played an important role in China’s economic reforms over the past two decades, bringing about great changes to the economy and soci-
To the Editor: Cutaneous metastasis of an internal malignancy is uncommon. Its clinical presentation is variable, although it is rarely seen in hepatocellular carcinoma (HCC).[1] For patients with HCC, the presence of...To the Editor: Cutaneous metastasis of an internal malignancy is uncommon. Its clinical presentation is variable, although it is rarely seen in hepatocellular carcinoma (HCC).[1] For patients with HCC, the presence of cutaneous metastases is associated with a dismal prognosis.展开更多
BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs ...BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs other second-line therapies in advanced HCC.METHODS This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.A comprehensive search of PubMed,EMBASE,Web of Science,and the Cochrane Library was performed on June 6,2025.Studies were included if they reported at least one relevant clinical outcome:Overall survival,progression-free survival,objective response rate,or disease control rate.Data was extracted independently by two reviewers.Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies.Pooled effect estimates were calculated using random-or fixed-effects models depending on the degree of heterogeneity.Sensitivity analyses and Egger’s test were performed to evaluate the robustness of the results and potential publication bias.RESULTS Nine studies met inclusion criteria.Regorafenib significantly improved overall survival compared to controls[weighted mean difference=2.54 months;95%confidence interval(CI):0.26-4.81;P<0.05],but no significant benefit was observed for progression-free survival(weighted mean difference=1.04;95%CI:-1.27 to 3.36).The pooled objective response rate showed no overall difference,though regorafenib was inferior to nivolumab in subgroup analysis(odds ratio=0.34;95% CI:0.20-0.58).Disease control rate did not differ significantly.No publication bias was detected.CONCLUSION Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.展开更多
AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM...AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of pr...BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospecti...AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Dark clouds are looming over the global economy. The Euro zone may only manage a paltry 1.5 percent growth next year. Meanwhile in the United States, labor, residential and consumer markets have all experienced a decl...Dark clouds are looming over the global economy. The Euro zone may only manage a paltry 1.5 percent growth next year. Meanwhile in the United States, labor, residential and consumer markets have all experienced a decline in growth. With rising fuel prices, a growing debt burden and a negative savings rate, the United States also is poised for further decline in consumption.展开更多
【选注者言:这是一则来自Calgary(卡尔加里,加拿大西南部城市)的消息,一个6岁的女孩从四楼,即12米的高度坠地,居然能保全性命,而仅有轻伤！文中的一个介词given,值得我们记学:Given the height that she fell,I think she’sextremely f...【选注者言:这是一则来自Calgary(卡尔加里,加拿大西南部城市)的消息,一个6岁的女孩从四楼,即12米的高度坠地,居然能保全性命,而仅有轻伤！文中的一个介词given,值得我们记学:Given the height that she fell,I think she’sextremely fortunate not to be more seriously injured。句首的介词Given的含义是“考虑到”。另如:Given ther imexperience,they’ve done a good job。汉译:考虑到他们缺乏经验,这工作他们做得不错。】展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteri...BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases pos...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.展开更多
Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(D...BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(DCC).These subtypes exhibit distinct clinical behaviors,treatment approaches,and outcomes.Despite advances in surgical and adjuvant therapies,the prognostic implications of tumor location remain unclear and inconsistently reported.Understanding these variations is essential for personalized management and staging refinement.We hypothesized that the anatomical subtype of CCA significantly influences prognostic outcomes and pathological features.AIM To compare prognostic outcomes and clinicopathological characteristics among IHCC,PHCC,and DCC based on current evidence.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed,EMBASE,and the Cochrane Library were searched,yielding 11 eligible retrospective comparative studies involving 14484 patients(IHCC:6260;PHCC:6895;DCC:1329).Outcomes assessed included overall survival(OS),lymph node metastasis,neural invasion,and vascular invasion.Statistical analyses were performed using RevMan 5.3 and Stata 13.0.RESULTS DCC demonstrated the most favorable prognosis among all subtypes.Despite the highest lymph node metastasis rate(DCC:56.9%),it was associated with better OS than PHCC and IHCC.Vascular invasion was more prevalent in IHCC(OR=1.66,95%CI:1.22-2.28,P=0.001).OS comparisons showed no significant difference between PHCC and IHCC(HR=1.02,P=0.88),while DCC showed consistent trends toward better survival against both.CONCLUSION Anatomical subtype is a significant prognostic factor in CCA.DCC patients experience superior outcomes despite aggressive lymphatic spread,suggesting better resectability and surgical outcomes.These insights underscore the need for subtype-specific management strategies and future prospective validation.展开更多
文摘THE non-public economy has played an important role in China’s economic reforms over the past two decades, bringing about great changes to the economy and soci-
基金This study was supported by grants from Guangzhou Science and Technology Plan General Project(No.201607010340)Guangdong Enterprise Technology Research and Development Fund Project(No.2013B021800044).
文摘To the Editor: Cutaneous metastasis of an internal malignancy is uncommon. Its clinical presentation is variable, although it is rarely seen in hepatocellular carcinoma (HCC).[1] For patients with HCC, the presence of cutaneous metastases is associated with a dismal prognosis.
文摘BACKGROUND Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma(HCC),but its comparative efficacy remains under evaluation.AIM To evaluate the efficacy and safety of regorafenib vs other second-line therapies in advanced HCC.METHODS This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.A comprehensive search of PubMed,EMBASE,Web of Science,and the Cochrane Library was performed on June 6,2025.Studies were included if they reported at least one relevant clinical outcome:Overall survival,progression-free survival,objective response rate,or disease control rate.Data was extracted independently by two reviewers.Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies.Pooled effect estimates were calculated using random-or fixed-effects models depending on the degree of heterogeneity.Sensitivity analyses and Egger’s test were performed to evaluate the robustness of the results and potential publication bias.RESULTS Nine studies met inclusion criteria.Regorafenib significantly improved overall survival compared to controls[weighted mean difference=2.54 months;95%confidence interval(CI):0.26-4.81;P<0.05],but no significant benefit was observed for progression-free survival(weighted mean difference=1.04;95%CI:-1.27 to 3.36).The pooled objective response rate showed no overall difference,though regorafenib was inferior to nivolumab in subgroup analysis(odds ratio=0.34;95% CI:0.20-0.58).Disease control rate did not differ significantly.No publication bias was detected.CONCLUSION Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.
基金Supported by the National Natural Science Foundation of China(No.82460215)National Natural Science Foundation of China Pre-experimental Project(No.2025GZRYSY006)+4 种基金2025 Youth Training Project of the Xi’an Municipal Health Commission(No.2025qn05)Xi’an Medical Research-Discipline Capacity Building Project(No.23YXYJ0002)Key R&D Plan of Shaanxi Province:Key Industrial Innovation Chain(Cluster)-Social Development Field(No.2022ZDLSF03-10)Research Incubation Fund of Xi’an People’s Hospital(Xi’an Fourth HospitalNo.LH-13).
文摘AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
文摘BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金Supported by the Faculty of Medicine,Prince of Songkla University.Wainipitapong S has received grants from the Faculty of Medicine,Prince of Songkla University。
文摘AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘Dark clouds are looming over the global economy. The Euro zone may only manage a paltry 1.5 percent growth next year. Meanwhile in the United States, labor, residential and consumer markets have all experienced a decline in growth. With rising fuel prices, a growing debt burden and a negative savings rate, the United States also is poised for further decline in consumption.
文摘【选注者言:这是一则来自Calgary(卡尔加里,加拿大西南部城市)的消息,一个6岁的女孩从四楼,即12米的高度坠地,居然能保全性命,而仅有轻伤！文中的一个介词given,值得我们记学:Given the height that she fell,I think she’sextremely fortunate not to be more seriously injured。句首的介词Given的含义是“考虑到”。另如:Given ther imexperience,they’ve done a good job。汉译:考虑到他们缺乏经验,这工作他们做得不错。】
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金Supported by National Natural Science Foundation of China,No.82002515,No.82273025 and No.82203460China Postdoctoral Science Foundation,No.2022TQ0070 and No.2022M710759Shanghai Municipal Commission of Science and Technology,No.22JC1403003,No.22XD1402200,No.19140901902 and No.22S31903800.
文摘BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
文摘BACKGROUND Cholangiocarcinoma(CCA)comprises heterogeneous malignancies arising at different anatomical locations:Intrahepatic cholangiocarcinoma(IHCC),perihilar cholangiocarcinoma(PHCC),and distal cholangiocarcinoma(DCC).These subtypes exhibit distinct clinical behaviors,treatment approaches,and outcomes.Despite advances in surgical and adjuvant therapies,the prognostic implications of tumor location remain unclear and inconsistently reported.Understanding these variations is essential for personalized management and staging refinement.We hypothesized that the anatomical subtype of CCA significantly influences prognostic outcomes and pathological features.AIM To compare prognostic outcomes and clinicopathological characteristics among IHCC,PHCC,and DCC based on current evidence.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed,EMBASE,and the Cochrane Library were searched,yielding 11 eligible retrospective comparative studies involving 14484 patients(IHCC:6260;PHCC:6895;DCC:1329).Outcomes assessed included overall survival(OS),lymph node metastasis,neural invasion,and vascular invasion.Statistical analyses were performed using RevMan 5.3 and Stata 13.0.RESULTS DCC demonstrated the most favorable prognosis among all subtypes.Despite the highest lymph node metastasis rate(DCC:56.9%),it was associated with better OS than PHCC and IHCC.Vascular invasion was more prevalent in IHCC(OR=1.66,95%CI:1.22-2.28,P=0.001).OS comparisons showed no significant difference between PHCC and IHCC(HR=1.02,P=0.88),while DCC showed consistent trends toward better survival against both.CONCLUSION Anatomical subtype is a significant prognostic factor in CCA.DCC patients experience superior outcomes despite aggressive lymphatic spread,suggesting better resectability and surgical outcomes.These insights underscore the need for subtype-specific management strategies and future prospective validation.
