To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC...To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same展开更多
We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the ...We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the International Journal of Surgery(1).This research conducted a single centre and retrospective analysis to compare the oncological survival in patients with pancreatic head ductal carcinoma(PHDC)undergoing the hybrid minimally invasive versus open pancreatoduodenectomy.The study found that the laparoscopic procedure was significantly superior in terms of intraoperative blood loss(575 vs.600 mL,P=0.02)and operative time(413 vs.427 min,P=0.03),and that patients who underwent hybrid laparoscopic resection of PHDC showed significantly improved oncological outcomes.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.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
The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiush...The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiushan Archipelago of Zhejiang Province,China since 2013.To evaluate the long-term effectiveness of these measures and address key knowledge gaps in population dynamics and migration ecology,we analyzed ten years(2015-2024)of banding and citizen science data,comprising 116 CCT and 3501 GCT resighting records.We estimated survival rates using both directly derived survival rate(based on resighting rate after two years)and Cormack-Jolly-Seber modeling,and examined migration connectivity and climate risks.Results showed robust juvenile survival:modeled survival for the tern chick population was lower in the first two years(63.9±12.0%)but exceeded 78%thereafter.This was also supported by resighting rate after two years:CCT 77.27%,GCT70.42%.A key divergence in post-breeding migration was identified:CCT moves northward to stopover sites such as Nantong,Rizhao,and Jiaozhou Bay,whereas GCT migrates southward.Climate data confirmed that northern stopover sites do not pose higher storm risks,indicating that CCT's northward migration is not a population liability.Furthermore,connectivity among breeding islands in Zhejiang and the Matsu Archipelago reveals a nascent coastal breeding network along China's coast.These findings underscore the importance of protecting both the northern migration route and the breeding island network to ensure full life-cycle conservation of CCT.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
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
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
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
Objective:To explore the application effect of digital intraoral scanning impression technique in oral implant restoration for periodontitis patients and analyze its impact on patients’Visual Analogue Scale(VAS)score...Objective:To explore the application effect of digital intraoral scanning impression technique in oral implant restoration for periodontitis patients and analyze its impact on patients’Visual Analogue Scale(VAS)scores.Methods:A total of 80 periodontitis patients who received implant restoration in our hospital from May 2023 to May 2025 were selected as research subjects.They were randomly divided into an observation group and a control group using a random number table method,with 40 cases in each group.The observation group used the digital intraoral scanning impression technique to obtain impressions,while the control group used the traditional silicone rubber impression technique.The impression-taking time,the number of prostheses try-ins,implant survival rate,periodontal health indicators(probing depth,gingival index,bleeding index),and VAS scores(pain during treatment and comfort after restoration)were compared between the two groups.Results:The observation group was superior to the control group in terms of impression-taking time,the number of prostheses try-ins,and implant survival rate(p<0.05).Six months after restoration,the improvement in periodontal health indicators in the observation group was significantly better than that in the control group(p<0.05).In addition,the pain VAS score of the observation group during treatment was lower than that of the control group,and the comfort VAS score after restoration was higher than that of the control group(p<0.05).Conclusion:Digital intraoral scanning impression technology can effectively enhance the efficiency and success rate of implant restoration in periodontitis patients,improve periodontal health,alleviate patients’discomfort during treatment,and increase post-restoration comfort,demonstrating high clinical application value.展开更多
Cascading failures pose a serious threat to the survivability of underwater unmanned swarm networks(UUSNs),significantly limiting their service ability in collaborative missions such as military reconnaissance and env...Cascading failures pose a serious threat to the survivability of underwater unmanned swarm networks(UUSNs),significantly limiting their service ability in collaborative missions such as military reconnaissance and environmental monitoring.Existing failure models primarily focus on power grids and traffic systems,and don't address the unique challenges of weak-communication UUSNs.In UUSNs,cascading failure present a complex and dynamic process driven by the coupling of unstable acoustic channels,passive node drift,adversarial attacks,and network heterogeneity.To address these challenges,a directed weighted graph model of UUSNs is first developed,in which node positions are updated according to ocean-current-driven drift and link weights reflect the probability of successful acoustic transmission.Building on this UUSNs graph model,a cascading failure model is proposed that integrates a normal-failure-recovery state-cycle mechanism,multiple attack strategies,and routingbased load redistribution.Finally,under a five-level connectivity UUSNs scheme,simulations are conducted to analyze how dynamic topology,network load,node recovery delay,and attack modes jointly affect network survivability.The main findings are:(1)moderate node drift can improve survivability by activating weak links;(2)based-energy routing(BER)outperform based-depth routing(BDR)in harsh conditions;(3)node self-recovery time is critical to network survivability;(4)traditional degree-based critical node metrics are inadequate for weak-communication UUSNs.These results provide a theoretical foundation for designing robust survivability mechanisms in weak-communication UUSNs.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
Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurr...Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurrence and survival rates in patients with early gastric cancer,providing evidence-based support for optimizing clinical surgical plans.Methods:A retrospective analysis was conducted on the clinical data of 100 patients with early gastric cancer who underwent surgical treatment at our hospital from October 2021 to October 2023.Patients were divided into Group D1(n=50)and Group D2(n=50)based on the extent of lymph node dissection.Group D1 underwent limited lymph node dissection(dissection of the first station of lymph nodes around the stomach),while Group D2 underwent standard lymph node dissection(dissection of the first and second stations of lymph nodes around the stomach).Surgical-related indicators,the incidence of postoperative complications,the 2-year recurrence rate,and the 2-year survival rate were compared between the two groups of patients.Results:The operative time,intraoperative blood loss,postoperative hospital stay,and the number of lymph nodes dissected were significantly higher in the D2 group than in the D1 group(all P<0.001).The overall incidence of postoperative complications was higher in the D1 group than in the D2 group,but the difference was not statistically significant(χ^(2)=0.884,P=0.766).After a 2-year follow-up,the recurrence rate was significantly higher in the D1 group than in the D2 group(χ^(2)=4.000,P=0.046).The 2-year survival rate was significantly lower in the D1 group than in the D2 group(χ^(2)=5.005,P=0.025).A total of 100 patients with early-stage gastric cancer were grouped according to the depth of invasion,degree of differentiation,and lymph node metastasis status,and the recurrence rates of different subgroups were compared.The results showed that the recurrence rate was higher in patients with T1b stage than in those with T1a stage(χ^(2)=5.005,P=0.025),higher in poorly differentiated patients than in moderately and well-differentiated patients(χ^(2)=4.155,P=0.042),and higher in patients with lymph node metastasis than in those without lymph node metastasis(χ^(2)=4.512,P=0.034).Conclusion:Compared with D1 limited lymph node dissection,D2 standard lymph node dissection can significantly reduce the postoperative recurrence rate and improve the 2-year survival rate in patients with early-stage gastric cancer without significantly increasing the risk of postoperative complications.Although the surgical trauma is slightly greater,the overall prognosis is better,making it a preferred surgical treatment option for patients with early-stage gastric cancer.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
Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)...Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.展开更多
The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably ass...Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.展开更多
In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. T...In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. The stresses, applied repeatedly at random cycle times, will causethe degradation of strength. In addition, the number of cycles in an interval is assumed to followa Poisson distribution. In the case of the strength and stress random variables following exponential distributions, the expression for the reliability of the proposed dynamic stress–strengthmodel is derived based on survival signature. The reliability is estimated by using the best linearunbiased estimation (BLUE). Considering the Type-II censored failure times, the best linear unbiased predictors (BLUP) for the unobserved coherent system failure times are developed basedon the observed failure times. Monte Carlo simulations are performed to compare the BLUE ofparameters with different values and compute the BLUP. A real data set is also analysed for anillustration of the findings.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
文摘To the Editor:A large international study has been recently published focusing on the combination of morphological aspects and alpha-fetoprotein(AFP)as predictors of survival in patients with hepatocellular cancer(HCC)treated with liver transplantation(LT)[1].As a matter of fact,morphology and biology represent the two sides of the same
基金supported by Guilin Science and Technology Plan Project(No.20220139-5-3)The Technology Project within the No.924 Hospital of PLA Joint Logistic Support Force(No.S2022FH01)+1 种基金Guangxi Healthcare Science and Technology Plan Project(No.Z-C20241574)The Fundamental Research Funds for the Central Universities of HIT.
文摘We read with great interest the article titled“Oncological survival in pancreatic head ductal carcinoma:hybrid minimally invasive versus open pancreatoduodenectomy-a single centre analysis”recently published in the International Journal of Surgery(1).This research conducted a single centre and retrospective analysis to compare the oncological survival in patients with pancreatic head ductal carcinoma(PHDC)undergoing the hybrid minimally invasive versus open pancreatoduodenectomy.The study found that the laparoscopic procedure was significantly superior in terms of intraoperative blood loss(575 vs.600 mL,P=0.02)and operative time(413 vs.427 min,P=0.03),and that patients who underwent hybrid laparoscopic resection of PHDC showed significantly improved oncological outcomes.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
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 National Natural Science Foundation of China(No.32370545)Key R&D Program of Zhejiang Province(No.2021C02044)Zhejiang Rare and Endangered Wildlife Rescue and Conservation Project(2021–2025)。
文摘The critically endangered Chinese Crested Tern(CThalasseus bernsteini,CCT)and its common flocking companion,the Greater Crested Tern(Thalasseus bergii,GCT),have been the focus of targeted recovery efforts in the Jiushan Archipelago of Zhejiang Province,China since 2013.To evaluate the long-term effectiveness of these measures and address key knowledge gaps in population dynamics and migration ecology,we analyzed ten years(2015-2024)of banding and citizen science data,comprising 116 CCT and 3501 GCT resighting records.We estimated survival rates using both directly derived survival rate(based on resighting rate after two years)and Cormack-Jolly-Seber modeling,and examined migration connectivity and climate risks.Results showed robust juvenile survival:modeled survival for the tern chick population was lower in the first two years(63.9±12.0%)but exceeded 78%thereafter.This was also supported by resighting rate after two years:CCT 77.27%,GCT70.42%.A key divergence in post-breeding migration was identified:CCT moves northward to stopover sites such as Nantong,Rizhao,and Jiaozhou Bay,whereas GCT migrates southward.Climate data confirmed that northern stopover sites do not pose higher storm risks,indicating that CCT's northward migration is not a population liability.Furthermore,connectivity among breeding islands in Zhejiang and the Matsu Archipelago reveals a nascent coastal breeding network along China's coast.These findings underscore the importance of protecting both the northern migration route and the breeding island network to ensure full life-cycle conservation of CCT.
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.
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 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.
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.
文摘Objective:To explore the application effect of digital intraoral scanning impression technique in oral implant restoration for periodontitis patients and analyze its impact on patients’Visual Analogue Scale(VAS)scores.Methods:A total of 80 periodontitis patients who received implant restoration in our hospital from May 2023 to May 2025 were selected as research subjects.They were randomly divided into an observation group and a control group using a random number table method,with 40 cases in each group.The observation group used the digital intraoral scanning impression technique to obtain impressions,while the control group used the traditional silicone rubber impression technique.The impression-taking time,the number of prostheses try-ins,implant survival rate,periodontal health indicators(probing depth,gingival index,bleeding index),and VAS scores(pain during treatment and comfort after restoration)were compared between the two groups.Results:The observation group was superior to the control group in terms of impression-taking time,the number of prostheses try-ins,and implant survival rate(p<0.05).Six months after restoration,the improvement in periodontal health indicators in the observation group was significantly better than that in the control group(p<0.05).In addition,the pain VAS score of the observation group during treatment was lower than that of the control group,and the comfort VAS score after restoration was higher than that of the control group(p<0.05).Conclusion:Digital intraoral scanning impression technology can effectively enhance the efficiency and success rate of implant restoration in periodontitis patients,improve periodontal health,alleviate patients’discomfort during treatment,and increase post-restoration comfort,demonstrating high clinical application value.
基金supported in part by the National Natural Science Foundation of China(Key Program)under Grant No.62031021。
文摘Cascading failures pose a serious threat to the survivability of underwater unmanned swarm networks(UUSNs),significantly limiting their service ability in collaborative missions such as military reconnaissance and environmental monitoring.Existing failure models primarily focus on power grids and traffic systems,and don't address the unique challenges of weak-communication UUSNs.In UUSNs,cascading failure present a complex and dynamic process driven by the coupling of unstable acoustic channels,passive node drift,adversarial attacks,and network heterogeneity.To address these challenges,a directed weighted graph model of UUSNs is first developed,in which node positions are updated according to ocean-current-driven drift and link weights reflect the probability of successful acoustic transmission.Building on this UUSNs graph model,a cascading failure model is proposed that integrates a normal-failure-recovery state-cycle mechanism,multiple attack strategies,and routingbased load redistribution.Finally,under a five-level connectivity UUSNs scheme,simulations are conducted to analyze how dynamic topology,network load,node recovery delay,and attack modes jointly affect network survivability.The main findings are:(1)moderate node drift can improve survivability by activating weak links;(2)based-energy routing(BER)outperform based-depth routing(BDR)in harsh conditions;(3)node self-recovery time is critical to network survivability;(4)traditional degree-based critical node metrics are inadequate for weak-communication UUSNs.These results provide a theoretical foundation for designing robust survivability mechanisms in weak-communication UUSNs.
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Shaanxi Provincial People’s Hospital Science and Technology Development Incubation Fund,“Research on the Role and Mechanism of PIGU in Regulating MUC-1 in Gastric Cancer Immune Escape”(Project No.:2023YJY-29)Shaanxi Provincial Natural Science Basic Research Program,“Research on the Mechanism and Clinical Significance of miR-140-5p Related to Gastric Cancer Recurrence and Metastasis”(Project No.:2023-JC-YB-639)。
文摘Early-stage gastric cancer;Extent of lymph node dissection;D1 dissection;D2 dissection;Recurrence rate;Survival rateObjective:To investigate the impact of different lymph node dissection scopes on postoperative recurrence and survival rates in patients with early gastric cancer,providing evidence-based support for optimizing clinical surgical plans.Methods:A retrospective analysis was conducted on the clinical data of 100 patients with early gastric cancer who underwent surgical treatment at our hospital from October 2021 to October 2023.Patients were divided into Group D1(n=50)and Group D2(n=50)based on the extent of lymph node dissection.Group D1 underwent limited lymph node dissection(dissection of the first station of lymph nodes around the stomach),while Group D2 underwent standard lymph node dissection(dissection of the first and second stations of lymph nodes around the stomach).Surgical-related indicators,the incidence of postoperative complications,the 2-year recurrence rate,and the 2-year survival rate were compared between the two groups of patients.Results:The operative time,intraoperative blood loss,postoperative hospital stay,and the number of lymph nodes dissected were significantly higher in the D2 group than in the D1 group(all P<0.001).The overall incidence of postoperative complications was higher in the D1 group than in the D2 group,but the difference was not statistically significant(χ^(2)=0.884,P=0.766).After a 2-year follow-up,the recurrence rate was significantly higher in the D1 group than in the D2 group(χ^(2)=4.000,P=0.046).The 2-year survival rate was significantly lower in the D1 group than in the D2 group(χ^(2)=5.005,P=0.025).A total of 100 patients with early-stage gastric cancer were grouped according to the depth of invasion,degree of differentiation,and lymph node metastasis status,and the recurrence rates of different subgroups were compared.The results showed that the recurrence rate was higher in patients with T1b stage than in those with T1a stage(χ^(2)=5.005,P=0.025),higher in poorly differentiated patients than in moderately and well-differentiated patients(χ^(2)=4.155,P=0.042),and higher in patients with lymph node metastasis than in those without lymph node metastasis(χ^(2)=4.512,P=0.034).Conclusion:Compared with D1 limited lymph node dissection,D2 standard lymph node dissection can significantly reduce the postoperative recurrence rate and improve the 2-year survival rate in patients with early-stage gastric cancer without significantly increasing the risk of postoperative complications.Although the surgical trauma is slightly greater,the overall prognosis is better,making it a preferred surgical treatment option for patients with early-stage gastric cancer.
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Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
文摘Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.
基金This work is supported by the National Natural Science Foundation of China[71571144,71401134,71171164,11701406]The Natural Science Basic Research Program of Shaanxi Province[2015JM1003]The Program of international Cooperation and Exchanges in Science and Technology Funded by Shaanxi Province[2016KW-033].
文摘In this paper, we proposed a dynamic stress–strength model for coherent system. It is supposedthat the system consists of n components with initial random strength and each component issubjected to random stresses. The stresses, applied repeatedly at random cycle times, will causethe degradation of strength. In addition, the number of cycles in an interval is assumed to followa Poisson distribution. In the case of the strength and stress random variables following exponential distributions, the expression for the reliability of the proposed dynamic stress–strengthmodel is derived based on survival signature. The reliability is estimated by using the best linearunbiased estimation (BLUE). Considering the Type-II censored failure times, the best linear unbiased predictors (BLUP) for the unobserved coherent system failure times are developed basedon the observed failure times. Monte Carlo simulations are performed to compare the BLUE ofparameters with different values and compute the BLUP. A real data set is also analysed for anillustration of the findings.
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.
