We found the qualitative study by Xu et al.on how patients feel about laparoscopic incisions under enhanced recovery after surgery(ERAS)protocols to be very interesting.1 Xu et al.carried out a qualitative study on pa...We found the qualitative study by Xu et al.on how patients feel about laparoscopic incisions under enhanced recovery after surgery(ERAS)protocols to be very interesting.1 Xu et al.carried out a qualitative study on patient experience with laparoscopic incisions under an ERAS protocol to highlight the problem of psychosocial and aesthetic concerns,which are often overlooked when planning surgical operations.This study,which involved semistructured interviews with sixteen people,aimed to narrow perioperative education and the decision-making process for incision site selection,thus making the processes more focused on patient priorities.The study is based on a timely but under-researched subject area;however,it is possible to outline four possible areas of improvement that would allow the study to be more transparent and,at the same time,more applicable to clinical practice.展开更多
Situs inversus totalis(SIT)is a rare congenital anomaly in which the major organs are reversed from their normal positions.In patients with SIT,the right-lobe graft must be placed in the left upper quadrant(LUQ).Howev...Situs inversus totalis(SIT)is a rare congenital anomaly in which the major organs are reversed from their normal positions.In patients with SIT,the right-lobe graft must be placed in the left upper quadrant(LUQ).However,hepatic outflow obstruction is a critical issue,often requiring radiologic intervention because of compression or kinking following graft regeneration of the vessels[1–3].Therefore,preoperative planning is essential to address the challenges of graft placement and vein reconstruction.Despite these complexities,we previously reported techniques using a reversed modified right-lobe(mRL)graft from a donor in a conventional recipient with SIT[2].Here,we successfully applied a similar concept.展开更多
Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endo...Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.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
BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.展开更多
BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is ...BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is often recommended.We present a surgical technique that was successfully used on four such patients to convert them to a knee fusion(KF)using a cephalomedullary nail.CASE SUMMARY Four patients with infected long stem revision knee replacements that refused AKA had a single stage removal of their infected revision total knee followed by a KF.They were all treated with a statically locked antegrade cephalomedullary fusion nail,augmented with antibiotic impregnated bone cement.All patients had successful limb salvage and were ambulatory with assistive devices at the time of last follow-up.All were infection free at an average follow-up of 25.5 months(range 16-31).CONCLUSION Single stage cephalomedullary nailing can result in a successful KF in patients with infected long stem revision total knees.展开更多
Background:The long-term outcomes of robotic-assisted surgery and the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio(NLR)in locally advanced rectal cancer(LARC)remain uncertain.This study a...Background:The long-term outcomes of robotic-assisted surgery and the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio(NLR)in locally advanced rectal cancer(LARC)remain uncertain.This study aimed to assess the long-term outcomes of patients with LARC undergoing robotic-assisted surgery and to determine the prognostic value of pretreatment NLR.Methods:We retrospectively reviewed 252 patients with LARC who were treated at a single medical center in Taiwan between January 2012 and January 2023.All patients underwent neoadjuvant concurrent chemoradiotherapy(CRT)followed by robotic-assisted surgery with total mesorectal excision(TME).Patients were stratified into four groups on the basis of pretreatment NLRs and carcinoembryonic antigen(CEA)levels.Univariate and multivariate analyses were conducted to identify prognostic indicators for overall survival(OS)and disease-free survival(DFS).Results:Patients with a pretreatment NLR of≥3.2 exhibited significantly worse OS and DFS compared with those with an NLR of<3.2(OS:94.4 vs.116.5 months,p=0.001;DFS:78.8 vs.101.7 months,p=0.003).Group A exhibited the poorest prognosis,whereas Group D had the most favorable outcomes.Multivariate analysis revealed NLR≥3.2 as an independent predictor of poor OS(hazard ratio[HR]=2.306,95%CI:1.149-3.747;p=0.001)and DFS(HR=2.055,95%CI:1.341-3.148;p=0.001).Conclusion:Neoadjuvant concurrent CRT followed by robotic-assisted TME is an effective treatment strategy for LARC.A higher pretreatment NLR(≥3.2)independently predicted worse OS and DFS.Stratification using the NLR in combination with CEA levels may enhance prognostic accuracy for patients undergoing robotic-assisted surgery for LARC.展开更多
This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehe...BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.展开更多
BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic f...BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.展开更多
Background:Early Hearing Detection and Intervention(EHDI)plays a critical role in improving language,cognitive,and socio-emotional outcomes for infants with hearing loss.In Nigeria,however,EHDI implementation remains ...Background:Early Hearing Detection and Intervention(EHDI)plays a critical role in improving language,cognitive,and socio-emotional outcomes for infants with hearing loss.In Nigeria,however,EHDI implementation remains limited by fragmented service delivery,uneven technological capacity,and sociocultural factors that delay timely diagnosis.This study explored the perspectives of paediatric audiologists and parents to provide a comprehensive understanding of the opportunities and challenges influencing early hearing care across diverse Nigerian settings.Methods:A mixed-methods design was employed across audiology facilities selected systematically from four Nigerian geopolitical zones.Twenty-five paediatric audiologists and twenty-three parents of children with congenital hearing loss participated.Quantitative data were collected using a structured questionnaire assessing awareness,diagnostic access,and intervention experiences.Qualitative data were obtained through semi-structured interviews and two focus group discussions.Thematic analysis followed Braun and Clarke's six-step framework,with dual coding,external auditing,and member validation to enhance credibility.Results:Quantitative findings demonstrated broad agreement on the diagnostic value of otoacoustic emissions(OAEs)and automated auditory brainstem responses(AABRs),the developmental benefits of early intervention,and the importance of active parental involvement.However,respondents identified persistent barriers including high costs of screening and therapy,poor public awareness of early hearing loss symptoms,and a critical shortage of trained personnel,and unequal distribution of diagnostic tools,particularly in rural and northern regions.Thematic analysis further underscored disparities in diagnostic capacity,sociocultural interpretations of deafness that delay clinical consultation,and economic constraints that hinder continuity of care.While families who accessed early intervention reported improved communication,social engagement,and learning readiness in their children,systemic gaps continue to limit widespread success.Conclusions:Despite growing technological capacity and awareness of EHDI benefits,significant structural,financial,and sociocultural challenges continue to impede timely diagnosis and intervention in Nigeria.Strengthening national policies,ensuring equitable distribution of diagnostic tools,expanding professional training,subsidising services,implementing culturally sensitive awareness campaigns and integration of Universal Newborn Hearing Screening into routine postnatal care are essential to improving outcomes for deaf infants.展开更多
Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantati...Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantation process including preoperative evaluation,donation,organ and patient transportation,surgery,postoperative recovery,and follow-up.This is a topic that has not been fully addressed yet,but its importance is being increasingly appreciated in surgery.The aim of this study was to investigate the carbon footprint associated with transplantation and propose sustainable mitigating solutions.A comprehensive review of the existing literature on transplantation was conducted and supplemented with findings from the broader fields of surgical and perioperative care,given the scarcity of available data.The analysis identified the most involved environmental factors and attempted to offer practical solutions based on current sustainability practices.Notably,no study has yet examined the carbon footprint associated with the entire transplantation procedure.Only five studies have attempted to assess the environmental impact of kidney or liver transplants,but they focused,almost explicitly,on specific steps of the process.By employing an extrapolative methodology from the broader surgical field,we determined that the primary contributors to the environmental impact of transplantation are energy,consumables and materials,anesthesia and pharmaceuticals,transportation,and water.This review offers practical solutions utilizing the 5R framework,emphasizing sustainability to ensure transplantation remains clinically and environmentally relevant.展开更多
BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical perf...BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.展开更多
As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodelin...As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.展开更多
Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including no...Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.展开更多
AIM To analyze the diagnostic performance of surveillance colonoscopy,computed tomography(CT),and tumor markers(TMs)in detecting CRC recurrence or metastasis during follow-up after CRC resection.Secondary objectives i...AIM To analyze the diagnostic performance of surveillance colonoscopy,computed tomography(CT),and tumor markers(TMs)in detecting CRC recurrence or metastasis during follow-up after CRC resection.Secondary objectives included degree of adherence to clinical practice guidelines surveillance recommendations and factors associated with adherence and all-cause and CRC mortality.METHODS The single-center retrospective cohort study including patients undergoing curative resection of stage I-III CRC during 2010-2015.Follow-up was performed using TMs every 6 months,yearly CT for 5 years,and colonoscopy at years 1 and 4.Demographic,primary tumor data,and results at follow-up were collected.RESULTS Of 574 included patients included,153 had recurrences or metastases.Of this group,136(88.9%)were diagnosed by CT,10(6.5%)by CT and colonoscopy,and 7(4.6%)by colonoscopy;only 67.8%showed TMs elevation.Adherence to follow-up recommendations was 68.8%for the first colonoscopy,74%for the first CT scan,and 96.6%for the first blood test;these values declined over time.Younger age at diagnosis[odds ratio(OR)0.93;95%CI:0.91-0.95],CRC stages I-II(OR 0.38;95%CI:0.24-0.61),and adherence to follow-up recommendations(OR 0.30;95%CI:0.20-0.46)were independently associated with lower risk for all-cause death at 5 years.CONCLUSION CT scan had the highest diagnostic yield.Adherence to follow-up recommendations was low and decreased during follow-up.Younger age at diagnosis,stage,and follow-up adherence were associated with lower 5-year mortality.展开更多
Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2)to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2)redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2)signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2)reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2)signaling.GBM cells were used to verify the role of H_(2)O_(2)signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2)via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2)levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More r...Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.展开更多
Endoscopic retrograde cholangiopancreatography(ERCP)plays a vital role in managing biliary and pancreatic diseases but carries a risk of severe complications that may require surgical intervention.This review focuses ...Endoscopic retrograde cholangiopancreatography(ERCP)plays a vital role in managing biliary and pancreatic diseases but carries a risk of severe complications that may require surgical intervention.This review focuses on the surgical management of key ERCP-related complications:Post-sphincterotomy bleeding,perforations,stent migration-induced perforations,and Dormia basket impaction.Although many complications can be managed endoscopically,surgery remains essential in refractory cases or when less invasive methods fail.Post-sphincterotomy bleeding,although often controlled endoscopically,may necessitate surgical ligation when hemorrhage persists.Perforations,classified by anatomical type,require tailored surgical approaches-primary repair for type I and biliary diversion with defect closure for types II and III.Stent migration-induced perforations,which may lead to peritonitis or abscess formation,often require surgery due to their variable clinical presentation and the lack of standardized management guidelines.Dormia basket impaction,although rare,may require advanced endoscopic techniques or laparoscopic retrieval if conservative measures prove ineffective.Early recognition,multidisciplinary collaboration,and individualized treatment strategies are pivotal in reducing morbidity and mortality.This review underscores evolving surgical approaches,emphasizing the importance of timely,patient-specific decisions to improve outcomes in severe ERCP-related complications.展开更多
文摘We found the qualitative study by Xu et al.on how patients feel about laparoscopic incisions under enhanced recovery after surgery(ERAS)protocols to be very interesting.1 Xu et al.carried out a qualitative study on patient experience with laparoscopic incisions under an ERAS protocol to highlight the problem of psychosocial and aesthetic concerns,which are often overlooked when planning surgical operations.This study,which involved semistructured interviews with sixteen people,aimed to narrow perioperative education and the decision-making process for incision site selection,thus making the processes more focused on patient priorities.The study is based on a timely but under-researched subject area;however,it is possible to outline four possible areas of improvement that would allow the study to be more transparent and,at the same time,more applicable to clinical practice.
文摘Situs inversus totalis(SIT)is a rare congenital anomaly in which the major organs are reversed from their normal positions.In patients with SIT,the right-lobe graft must be placed in the left upper quadrant(LUQ).However,hepatic outflow obstruction is a critical issue,often requiring radiologic intervention because of compression or kinking following graft regeneration of the vessels[1–3].Therefore,preoperative planning is essential to address the challenges of graft placement and vein reconstruction.Despite these complexities,we previously reported techniques using a reversed modified right-lobe(mRL)graft from a donor in a conventional recipient with SIT[2].Here,we successfully applied a similar concept.
文摘Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.
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BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.
文摘BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is often recommended.We present a surgical technique that was successfully used on four such patients to convert them to a knee fusion(KF)using a cephalomedullary nail.CASE SUMMARY Four patients with infected long stem revision knee replacements that refused AKA had a single stage removal of their infected revision total knee followed by a KF.They were all treated with a statically locked antegrade cephalomedullary fusion nail,augmented with antibiotic impregnated bone cement.All patients had successful limb salvage and were ambulatory with assistive devices at the time of last follow-up.All were infection free at an average follow-up of 25.5 months(range 16-31).CONCLUSION Single stage cephalomedullary nailing can result in a successful KF in patients with infected long stem revision total knees.
基金supported by grants through funding from the National Science and Technology Council(NSTC112-2314-B-037-050-MY3,NSTC114-2314-B-037-103-MY3,NSTC114-2321-B-037-003)the Ministry of Health and Welfare(MOHW113-TDU-B-222-134014)+2 种基金funded by the health and welfare surcharge of on tobacco products,and the Kaohsiung Medical University Hospital(KMUH113-3R31,KMUH113-3R32,KMUH113-3R33,KMUH113-3M58,KMUH113-3M59,KMUH-S11412,KMUH-SH11403)Kaohsiung Medical University Research Center Grant(KMU-TC113A04)supported by the Grant of Taiwan Precision Medicine Initiative and Taiwan Biobank,Academia Sinica,Taiwan.
文摘Background:The long-term outcomes of robotic-assisted surgery and the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio(NLR)in locally advanced rectal cancer(LARC)remain uncertain.This study aimed to assess the long-term outcomes of patients with LARC undergoing robotic-assisted surgery and to determine the prognostic value of pretreatment NLR.Methods:We retrospectively reviewed 252 patients with LARC who were treated at a single medical center in Taiwan between January 2012 and January 2023.All patients underwent neoadjuvant concurrent chemoradiotherapy(CRT)followed by robotic-assisted surgery with total mesorectal excision(TME).Patients were stratified into four groups on the basis of pretreatment NLRs and carcinoembryonic antigen(CEA)levels.Univariate and multivariate analyses were conducted to identify prognostic indicators for overall survival(OS)and disease-free survival(DFS).Results:Patients with a pretreatment NLR of≥3.2 exhibited significantly worse OS and DFS compared with those with an NLR of<3.2(OS:94.4 vs.116.5 months,p=0.001;DFS:78.8 vs.101.7 months,p=0.003).Group A exhibited the poorest prognosis,whereas Group D had the most favorable outcomes.Multivariate analysis revealed NLR≥3.2 as an independent predictor of poor OS(hazard ratio[HR]=2.306,95%CI:1.149-3.747;p=0.001)and DFS(HR=2.055,95%CI:1.341-3.148;p=0.001).Conclusion:Neoadjuvant concurrent CRT followed by robotic-assisted TME is an effective treatment strategy for LARC.A higher pretreatment NLR(≥3.2)independently predicted worse OS and DFS.Stratification using the NLR in combination with CEA levels may enhance prognostic accuracy for patients undergoing robotic-assisted surgery for LARC.
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
文摘BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.
文摘BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.
文摘Background:Early Hearing Detection and Intervention(EHDI)plays a critical role in improving language,cognitive,and socio-emotional outcomes for infants with hearing loss.In Nigeria,however,EHDI implementation remains limited by fragmented service delivery,uneven technological capacity,and sociocultural factors that delay timely diagnosis.This study explored the perspectives of paediatric audiologists and parents to provide a comprehensive understanding of the opportunities and challenges influencing early hearing care across diverse Nigerian settings.Methods:A mixed-methods design was employed across audiology facilities selected systematically from four Nigerian geopolitical zones.Twenty-five paediatric audiologists and twenty-three parents of children with congenital hearing loss participated.Quantitative data were collected using a structured questionnaire assessing awareness,diagnostic access,and intervention experiences.Qualitative data were obtained through semi-structured interviews and two focus group discussions.Thematic analysis followed Braun and Clarke's six-step framework,with dual coding,external auditing,and member validation to enhance credibility.Results:Quantitative findings demonstrated broad agreement on the diagnostic value of otoacoustic emissions(OAEs)and automated auditory brainstem responses(AABRs),the developmental benefits of early intervention,and the importance of active parental involvement.However,respondents identified persistent barriers including high costs of screening and therapy,poor public awareness of early hearing loss symptoms,and a critical shortage of trained personnel,and unequal distribution of diagnostic tools,particularly in rural and northern regions.Thematic analysis further underscored disparities in diagnostic capacity,sociocultural interpretations of deafness that delay clinical consultation,and economic constraints that hinder continuity of care.While families who accessed early intervention reported improved communication,social engagement,and learning readiness in their children,systemic gaps continue to limit widespread success.Conclusions:Despite growing technological capacity and awareness of EHDI benefits,significant structural,financial,and sociocultural challenges continue to impede timely diagnosis and intervention in Nigeria.Strengthening national policies,ensuring equitable distribution of diagnostic tools,expanding professional training,subsidising services,implementing culturally sensitive awareness campaigns and integration of Universal Newborn Hearing Screening into routine postnatal care are essential to improving outcomes for deaf infants.
文摘Green transplant refers to the realization of the importance of understanding and improving the environmental footprint of transplantation through sustainable practices.This involves assessing the entire transplantation process including preoperative evaluation,donation,organ and patient transportation,surgery,postoperative recovery,and follow-up.This is a topic that has not been fully addressed yet,but its importance is being increasingly appreciated in surgery.The aim of this study was to investigate the carbon footprint associated with transplantation and propose sustainable mitigating solutions.A comprehensive review of the existing literature on transplantation was conducted and supplemented with findings from the broader fields of surgical and perioperative care,given the scarcity of available data.The analysis identified the most involved environmental factors and attempted to offer practical solutions based on current sustainability practices.Notably,no study has yet examined the carbon footprint associated with the entire transplantation procedure.Only five studies have attempted to assess the environmental impact of kidney or liver transplants,but they focused,almost explicitly,on specific steps of the process.By employing an extrapolative methodology from the broader surgical field,we determined that the primary contributors to the environmental impact of transplantation are energy,consumables and materials,anesthesia and pharmaceuticals,transportation,and water.This review offers practical solutions utilizing the 5R framework,emphasizing sustainability to ensure transplantation remains clinically and environmentally relevant.
文摘BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.
基金College of Graduate Studies,Medical University of South Carolina,Grant/Award Number:SCTR 2305National Heart,Lung,and Blood Institute,Grant/Award Number:1U01HL169361-01NIH:NCATS,Grant/Award Number:UL1TR001450。
文摘As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.
文摘Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.
基金Supported by Instituto de Investigación Sanitaria ISABIAL,No.P42022-0275.
文摘AIM To analyze the diagnostic performance of surveillance colonoscopy,computed tomography(CT),and tumor markers(TMs)in detecting CRC recurrence or metastasis during follow-up after CRC resection.Secondary objectives included degree of adherence to clinical practice guidelines surveillance recommendations and factors associated with adherence and all-cause and CRC mortality.METHODS The single-center retrospective cohort study including patients undergoing curative resection of stage I-III CRC during 2010-2015.Follow-up was performed using TMs every 6 months,yearly CT for 5 years,and colonoscopy at years 1 and 4.Demographic,primary tumor data,and results at follow-up were collected.RESULTS Of 574 included patients included,153 had recurrences or metastases.Of this group,136(88.9%)were diagnosed by CT,10(6.5%)by CT and colonoscopy,and 7(4.6%)by colonoscopy;only 67.8%showed TMs elevation.Adherence to follow-up recommendations was 68.8%for the first colonoscopy,74%for the first CT scan,and 96.6%for the first blood test;these values declined over time.Younger age at diagnosis[odds ratio(OR)0.93;95%CI:0.91-0.95],CRC stages I-II(OR 0.38;95%CI:0.24-0.61),and adherence to follow-up recommendations(OR 0.30;95%CI:0.20-0.46)were independently associated with lower risk for all-cause death at 5 years.CONCLUSION CT scan had the highest diagnostic yield.Adherence to follow-up recommendations was low and decreased during follow-up.Younger age at diagnosis,stage,and follow-up adherence were associated with lower 5-year mortality.
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2)to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2)redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2)signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2)reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2)signaling.GBM cells were used to verify the role of H_(2)O_(2)signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2)via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2)levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
基金supported by the National Natural Science Foundation of China,Nos.82404892(to QY),82061160374(to ZZ)the Science and Technology Development Fund,Macao Special Administrative Region,China,Nos.0023/2020/AFJ,0035/2020/AGJ+2 种基金the University of Macao Research Grant,Nos.MYRG2022-00248-ICMS,MYRG-CRG2022-00010-ICMS(to MPMH)the Natural Science Foundation of Guangdong Province,No.2024A1515012818(to ZZ)the Fundamental Research Funds for the Central Universities,No.21623114(to ZZ).
文摘Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.
文摘Endoscopic retrograde cholangiopancreatography(ERCP)plays a vital role in managing biliary and pancreatic diseases but carries a risk of severe complications that may require surgical intervention.This review focuses on the surgical management of key ERCP-related complications:Post-sphincterotomy bleeding,perforations,stent migration-induced perforations,and Dormia basket impaction.Although many complications can be managed endoscopically,surgery remains essential in refractory cases or when less invasive methods fail.Post-sphincterotomy bleeding,although often controlled endoscopically,may necessitate surgical ligation when hemorrhage persists.Perforations,classified by anatomical type,require tailored surgical approaches-primary repair for type I and biliary diversion with defect closure for types II and III.Stent migration-induced perforations,which may lead to peritonitis or abscess formation,often require surgery due to their variable clinical presentation and the lack of standardized management guidelines.Dormia basket impaction,although rare,may require advanced endoscopic techniques or laparoscopic retrieval if conservative measures prove ineffective.Early recognition,multidisciplinary collaboration,and individualized treatment strategies are pivotal in reducing morbidity and mortality.This review underscores evolving surgical approaches,emphasizing the importance of timely,patient-specific decisions to improve outcomes in severe ERCP-related complications.
