BACKGROUND Urolithiasisposes challenges in patients with chronic kidney disease(CKD),necessitating careful consideration of surgical interventions due to potential complications.AIM To assess the safety,feasibility,an...BACKGROUND Urolithiasisposes challenges in patients with chronic kidney disease(CKD),necessitating careful consideration of surgical interventions due to potential complications.AIM To assess the safety,feasibility,and efficacy of surgical interventions for urolithiasis in CKD patients.METHODS Systematic review adhering to PRISMA guidelines.Comprehensive searches of PubMed,Scopus,Cochrane Library,Web of Science,and Embase were conducted for studies published from January 2014 to June 2024.Studies involving adult patients(≥18 years)with CKD undergoing surgical interventions for urolithiasis,including randomized controlled trials,cohort studies,case-control studies,and observational studies.Studies involving pediatric patients,those not specifically addressing CKD patients,review articles,commentaries,and editorials.Despite an extensive search,only six studies met the strict inclusion criteria,reflecting the limited available data on this topic.This limitation has been acknowledged and discussed.RESULTS A total of 6 studies met the inclusion criteria,encompassing a diverse range of surgical interventions such as percutaneous nephrolithotomy(PCNL),ureteroscopy(URS),and extracorporeal shock wave lithotripsy(ESWL).Perioperative and postoperative complications varied across studies,with bleeding,infection,and acute kidney injury being the most common.The risk of complications was higher in patients with advanced CKD.Technical success rates were generally high,but feasibility was influenced by patientspecific factors such as CKD stage and comorbidities.Modifications to standard surgical techniques were often necessary.Stone-free rates and recurrence rates varied,with PCNL generally achieving higher stone-free rates compared to URS and ESWL.Long-term outcomes on renal function were inconsistent,highlighting the need for individualized treatment plans.CONCLUSION Surgical interventions for urolithiasis in CKD patients are associated with significant risks but can be effective in achieving stone clearance and symptom relief.The safety,feasibility,and efficacy of these interventions depend on patient-specific factors,necessitating a tailored approach.Further high-quality studies are needed to develop standardized guidelines and improve clinical outcomes in this complex patient population.展开更多
BACKGROUND Surgically created arterio-venous fistulas(AVFs)are the gold standard for haemodialysis access for patients with end-stage renal disease.Standard practice of AVF creation involves selecting the non-dominant...BACKGROUND Surgically created arterio-venous fistulas(AVFs)are the gold standard for haemodialysis access for patients with end-stage renal disease.Standard practice of AVF creation involves selecting the non-dominant upper limb and starting with most distally with radio-cephalic arterio-venous fistula.The primary patency rate of radio-cephalic arterio-venous fistula varies from 20%-25%.It has been suggested the neointimal hyperplasia at the mobilized venous segment causes stenosis of the anastomosis.Therefore,the radial artery deviation and reimplantation(RADAR)technique,in which the vein is minimally mobilized,should result in a higher success rate.AIM To compare the RADAR technique with classical technique in creation of AVF including:(1)Success rate;(2)Time to maturation;(3)Duration of surgery;and(4)Complication rate.METHODS In our study we recruited 94 patients in two randomized groups and performed the AVF by the classical method or the RADAR method.RESULTS The RADAR group had higher primary success rate(P=0.007),less rate of complications(P=0.04),shorter duration of surgery(P=0.00)and early time to maturation(0.001)when compared with the classical group.The RADAR procedure is a safe and a more efficient alternative to the current classical method of AVF creation.Longer duration of follow-up is required to assess the long-term outcomes in the future.CONCLUSION The RADAR procedure is a safe and more efficient alternative to the current classical method of AVF creation.Longer duration of follow-up is required to assess the long-term outcomes in the future.展开更多
Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific app...Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific approach.This study explored the potential of an inflammatory marker-based nomograph model,highlighting the relapse-free survival-associated risk factors prognostic potential in patients with GIST.The author assessed 124 samples from patients with GIST to find an association between inflammatory markers and tumor size in a retrospective study using multivariate regression analysis.Further,a nomogram model was developed to identify the independent risk factors for the prognosis.GIST clinical treatment can use preoperative monocyte/lymphocyte ratio and platelet/lymphocyte ratio for relapse-free survival prognosis as independent factors.展开更多
Zhou et al’s investigation on the creation of a non-invasive deep learning(DL)method for colorectal tumor immune microenvironment evaluation using preoperative computed tomography(CT)radiomics published in the World ...Zhou et al’s investigation on the creation of a non-invasive deep learning(DL)method for colorectal tumor immune microenvironment evaluation using preoperative computed tomography(CT)radiomics published in the World Journal of Gastrointestinal Oncology is thorough and scientific.The study analyzed preoperative CT images of 315 confirmed colorectal cancer patients,using manual regions of interest to extract DL features.The study developed a DL model using CT images and histopathological images to predict immune-related indicators in colorectal cancer patients.Pathological(tumor-stroma ratio,tumor-infiltrating lymphocytes infiltration,immunohistochemistry,tumor immune microenvir-onment and immune score)parameters and radiomics(CT imaging and model construction)data were combined to generate artificial intelligence-powered models.Clinical benefit and goodness of fit of the models were assessed using receiver operating characteristic,area under curve and decision curve analysis.The developed DL-based radiomics prediction model for non-invasive evaluation of tumor markers demonstrated potential for personalized treatment planning and immunotherapy strategies in colorectal cancer patients.The study,involving a small group from a single medical center,lacks inclusion/exclusion criteria and should include clinicopathological features for valuable therapeutic practice insights in colorectal cancer patients.展开更多
BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectil...BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectile dysfunction(ED)is highly prevalent due to factors such as underlying comorbidities,including diabetes and hypertension,and the physiological effects of long-term dialysis.Kidney transplantation(KTx)has been proposed as a potential intervention to mitigate the effects of ED by restoring renal function and improving hormonal balance.However,the evidence surrounding the effectiveness of KTx in improving sexual function,specifically erectile function(EF),remains inconclusive.This systematic review and meta-analysis aim to evaluate the effects of KTx on sexual dysfunction(SexDys),particularly ED,in male ESRD patients.AIM To evaluate the benefits and potential harms of KTx compared to other forms of renal replacement therapy in improving EF in adult males with ESRD,assessed using the international index of EF(IIEF),to survey the prevalence of SexDys in this population,and to assess the correlation between various factors and SexDys through regression analysis.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,Scopus,Clinical-Trials.gov,and Google Scholar was conducted,following the PRISMA 2020 guidelines.Prospective and retrospective cohort studies,as well as cross-sectional studies assessing EF pre-and post-transplantation,were included.These studies used validated tools such as the IIEF to measure EF.Meta-analyses were performed using a random-effects model to estimate standardized mean differences(SMD)and hazard ratios(HR)with 95%confidence intervals(CI).Heterogeneity was assessed using the I²statistic,and publication bias was evaluated with a funnel plot and the Egger’s test.RESULTS A total of 2419 studies were identified,with 362 abstracts screened and 193 full-text articles reviewed.Ultimately,11 studies were included for qualitative analysis and 7 for quantitative synthesis.The random effects model for SMD yielded a combined estimate of 0.43(95%CI:-0.20-1.07),indicating a small but non-significant improvement in EF post-transplantation.The heterogeneity across studies was substantial(I²=90%),reflecting significant variability in outcomes.Subgroup analysis showed greater improvements in EF among living-donor transplant recipients compared to those receiving organs from deceased donors.Despite this trend,the overall result for changes in EF was not statistically significant(P=0.15).Additionally,the combined HR from the meta-analysis was 2.87(95%CI:1.76-4.69),suggesting that KTx significantly increases the likelihood of improved EF,though variability between studies persisted(I²=63%).CONCLUSION While KTx offers some promise for improving EF in male ESRD patients,the overall evidence remains inconclusive due to high heterogeneity between studies and a lack of statistical significance in the combined results.Despite this,individual studies suggest that KTx may lead to significant improvements in EF for certain subgroups,particularly living-donor recipients.Future research should focus on larger,well-designed cohort studies with standardized outcome measures to provide more definitive conclusions.Addressing SexDys as part of routine care for ESRD patients undergoing KTx is crucial to improving their overall quality of life.However,adjunct therapies such as phosphodiesterase type 5 inhibitors may be necessary for those who do not experience adequate improvements post-transplantation.展开更多
Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)ri...Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)risk in the Chinese population is a scientific approach.This study explores the susceptibility of ACVR1C polymorphism towards ESCC in the Chinese population,highlighting the polymorphism’s potentiality as an early diagnostic and therapeutic target.The author assessed about a thousand ESCC Chinese patients’samples for ACVR1C SNPs in a hospital-based cohort study using the ligation detection reaction method.Further,the hypothesis was tested using appropriate statistical genetic models and stratified analysis.ACVR1C SNPs can help assess ESCC susceptibility stratification and provide valuable information for individual diagnosis and treatment of ESCC patients.In order to account for confounding variables,find genuine SNP-disease relationships,boost statistical power,and make biological interpretation easier,it is imperative that genetic association studies of ESCC incorporate pertinent clinical aspects.展开更多
The investigation by Zhu et al on the assessment of cellular proliferation markers to assist clinical decision-making in patients with hepatocellular carcinoma(HCC)using a machine learning model-based approach is a sc...The investigation by Zhu et al on the assessment of cellular proliferation markers to assist clinical decision-making in patients with hepatocellular carcinoma(HCC)using a machine learning model-based approach is a scientific approach.This study looked into the possibilities of using a Ki-67(a marker for cell proliferation)expression-based machine learning model to help doctors make decisions about treatment options for patients with HCC before surgery.The study used reconstructed tomography images of 164 patients with confirmed HCC from the intratumoral and peritumoral regions.The features were chosen using various statistical methods,including least absolute shrinkage and selection operator regression.Also,a nomogram was made using Radscore and clinical risk factors.It was tested for its ability to predict receiver operating characteristic curves and calibration curves,and its clinical benefits were found using decision curve analysis.The calibration curve demonstrated excellent consistency between predicted and actual probability,and the decision curve confirmed its clinical benefit.The proposed model is helpful for treating patients with HCC because the predicted and actual probabilities are very close to each other,as shown by the decision curve analysis.Further prospective studies are required,incorporating a multicenter and large sample size design,additional relevant exclusion criteria,information on tumors(size,number,and grade),and cancer stage to strengthen the clinical benefit in patients with HCC.展开更多
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes...Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.展开更多
Insulin,a small protein with 51 amino acids synthesized by pancreatic β-cells,is crucial to sustain glucose homeostasis at biochemical and molecular levels.Numerous metabolic dysfunctions are related to insulin-media...Insulin,a small protein with 51 amino acids synthesized by pancreatic β-cells,is crucial to sustain glucose homeostasis at biochemical and molecular levels.Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis.One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus(DM)(type 1,type 2,and gestational).Insulin resistance(IR)is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions.Metabolic syndrome(MS)is another pathophysiological condition that is associated with IR,hypertension,and obesity.Further,several other pathophysiological disorders/diseases are associated with the insulin malfunctioning,which include polycystic ovary syndrome,neuronal disorders,and cancer.Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms.Literature revealed that different biochemical events,molecular signaling pathways,microRNAs,and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM,insuloma,neurological disorder,MS,and cancer.In this review,we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.展开更多
Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate cancer.Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate ...Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate cancer.Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer(CRPC).Present research establishes that prostate cancer stem-like cells(CSCs)play a central role in the development of treatment resistance followed by disease progression.Prostate CSCs are capable of self-renewal,differentiation,and regenerating tumor heterogeneity.The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants,epigenetic and genetic modifications leading to alteration in the tumor microenvironment,changes in ATP-binding cassette(ABC)transporters,and adaptations in molecular signaling pathways.ADT reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1(ALDH1A1),Prominin 1(PROM1/CD133),Indian blood group(CD44),SRY-Box Transcription Factor 2(Sox2),POU Class 5 Homeobox 1(POU5F1/Oct4),Nanog and ABC transporters.These markers indicate enhanced self-renewal and stemness stimulating CRPC evolution,metastatic colonization,and resistance to antiandrogens.In this review,we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC,their isolation,identification and characterization,as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities.展开更多
Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer treatment.Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct...Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer treatment.Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct mechanisms and pathways.Understanding the molecular mechanisms involved in drug resistance remains an important area of research for identification of precise targets and drug discovery to improve therapeutic outcomes.This review highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.展开更多
Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were use...Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.展开更多
Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiratero...Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling pathways.In this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC emergence.Evolving knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.展开更多
Epidemiological studies suggest a close association between diet and cancer initiation,which provides evidence that the dietary components may be effectively developed as chemopreventive agents[1].These pieces of evid...Epidemiological studies suggest a close association between diet and cancer initiation,which provides evidence that the dietary components may be effectively developed as chemopreventive agents[1].These pieces of evidence are further supported by several case-control and cohort studies,which overwhelmingly support a converse association between the intake of phytochemicals and cancer risk[2,3].A number of clinical studies have been conducted demonstrating that dietary phytochemicals have the ability to inhibit tumorigenesis[4].Components presenting in fruit and vegetables termed“bioactive”phytochemicals belong to several classes of micronutrients,including flavonoids,polyphenols,and dietary fiber.These components have the ability to reduce the cancer risk alone or by interactions between them.展开更多
文摘BACKGROUND Urolithiasisposes challenges in patients with chronic kidney disease(CKD),necessitating careful consideration of surgical interventions due to potential complications.AIM To assess the safety,feasibility,and efficacy of surgical interventions for urolithiasis in CKD patients.METHODS Systematic review adhering to PRISMA guidelines.Comprehensive searches of PubMed,Scopus,Cochrane Library,Web of Science,and Embase were conducted for studies published from January 2014 to June 2024.Studies involving adult patients(≥18 years)with CKD undergoing surgical interventions for urolithiasis,including randomized controlled trials,cohort studies,case-control studies,and observational studies.Studies involving pediatric patients,those not specifically addressing CKD patients,review articles,commentaries,and editorials.Despite an extensive search,only six studies met the strict inclusion criteria,reflecting the limited available data on this topic.This limitation has been acknowledged and discussed.RESULTS A total of 6 studies met the inclusion criteria,encompassing a diverse range of surgical interventions such as percutaneous nephrolithotomy(PCNL),ureteroscopy(URS),and extracorporeal shock wave lithotripsy(ESWL).Perioperative and postoperative complications varied across studies,with bleeding,infection,and acute kidney injury being the most common.The risk of complications was higher in patients with advanced CKD.Technical success rates were generally high,but feasibility was influenced by patientspecific factors such as CKD stage and comorbidities.Modifications to standard surgical techniques were often necessary.Stone-free rates and recurrence rates varied,with PCNL generally achieving higher stone-free rates compared to URS and ESWL.Long-term outcomes on renal function were inconsistent,highlighting the need for individualized treatment plans.CONCLUSION Surgical interventions for urolithiasis in CKD patients are associated with significant risks but can be effective in achieving stone clearance and symptom relief.The safety,feasibility,and efficacy of these interventions depend on patient-specific factors,necessitating a tailored approach.Further high-quality studies are needed to develop standardized guidelines and improve clinical outcomes in this complex patient population.
文摘BACKGROUND Surgically created arterio-venous fistulas(AVFs)are the gold standard for haemodialysis access for patients with end-stage renal disease.Standard practice of AVF creation involves selecting the non-dominant upper limb and starting with most distally with radio-cephalic arterio-venous fistula.The primary patency rate of radio-cephalic arterio-venous fistula varies from 20%-25%.It has been suggested the neointimal hyperplasia at the mobilized venous segment causes stenosis of the anastomosis.Therefore,the radial artery deviation and reimplantation(RADAR)technique,in which the vein is minimally mobilized,should result in a higher success rate.AIM To compare the RADAR technique with classical technique in creation of AVF including:(1)Success rate;(2)Time to maturation;(3)Duration of surgery;and(4)Complication rate.METHODS In our study we recruited 94 patients in two randomized groups and performed the AVF by the classical method or the RADAR method.RESULTS The RADAR group had higher primary success rate(P=0.007),less rate of complications(P=0.04),shorter duration of surgery(P=0.00)and early time to maturation(0.001)when compared with the classical group.The RADAR procedure is a safe and a more efficient alternative to the current classical method of AVF creation.Longer duration of follow-up is required to assess the long-term outcomes in the future.CONCLUSION The RADAR procedure is a safe and more efficient alternative to the current classical method of AVF creation.Longer duration of follow-up is required to assess the long-term outcomes in the future.
文摘Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific approach.This study explored the potential of an inflammatory marker-based nomograph model,highlighting the relapse-free survival-associated risk factors prognostic potential in patients with GIST.The author assessed 124 samples from patients with GIST to find an association between inflammatory markers and tumor size in a retrospective study using multivariate regression analysis.Further,a nomogram model was developed to identify the independent risk factors for the prognosis.GIST clinical treatment can use preoperative monocyte/lymphocyte ratio and platelet/lymphocyte ratio for relapse-free survival prognosis as independent factors.
文摘Zhou et al’s investigation on the creation of a non-invasive deep learning(DL)method for colorectal tumor immune microenvironment evaluation using preoperative computed tomography(CT)radiomics published in the World Journal of Gastrointestinal Oncology is thorough and scientific.The study analyzed preoperative CT images of 315 confirmed colorectal cancer patients,using manual regions of interest to extract DL features.The study developed a DL model using CT images and histopathological images to predict immune-related indicators in colorectal cancer patients.Pathological(tumor-stroma ratio,tumor-infiltrating lymphocytes infiltration,immunohistochemistry,tumor immune microenvir-onment and immune score)parameters and radiomics(CT imaging and model construction)data were combined to generate artificial intelligence-powered models.Clinical benefit and goodness of fit of the models were assessed using receiver operating characteristic,area under curve and decision curve analysis.The developed DL-based radiomics prediction model for non-invasive evaluation of tumor markers demonstrated potential for personalized treatment planning and immunotherapy strategies in colorectal cancer patients.The study,involving a small group from a single medical center,lacks inclusion/exclusion criteria and should include clinicopathological features for valuable therapeutic practice insights in colorectal cancer patients.
文摘BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectile dysfunction(ED)is highly prevalent due to factors such as underlying comorbidities,including diabetes and hypertension,and the physiological effects of long-term dialysis.Kidney transplantation(KTx)has been proposed as a potential intervention to mitigate the effects of ED by restoring renal function and improving hormonal balance.However,the evidence surrounding the effectiveness of KTx in improving sexual function,specifically erectile function(EF),remains inconclusive.This systematic review and meta-analysis aim to evaluate the effects of KTx on sexual dysfunction(SexDys),particularly ED,in male ESRD patients.AIM To evaluate the benefits and potential harms of KTx compared to other forms of renal replacement therapy in improving EF in adult males with ESRD,assessed using the international index of EF(IIEF),to survey the prevalence of SexDys in this population,and to assess the correlation between various factors and SexDys through regression analysis.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,Scopus,Clinical-Trials.gov,and Google Scholar was conducted,following the PRISMA 2020 guidelines.Prospective and retrospective cohort studies,as well as cross-sectional studies assessing EF pre-and post-transplantation,were included.These studies used validated tools such as the IIEF to measure EF.Meta-analyses were performed using a random-effects model to estimate standardized mean differences(SMD)and hazard ratios(HR)with 95%confidence intervals(CI).Heterogeneity was assessed using the I²statistic,and publication bias was evaluated with a funnel plot and the Egger’s test.RESULTS A total of 2419 studies were identified,with 362 abstracts screened and 193 full-text articles reviewed.Ultimately,11 studies were included for qualitative analysis and 7 for quantitative synthesis.The random effects model for SMD yielded a combined estimate of 0.43(95%CI:-0.20-1.07),indicating a small but non-significant improvement in EF post-transplantation.The heterogeneity across studies was substantial(I²=90%),reflecting significant variability in outcomes.Subgroup analysis showed greater improvements in EF among living-donor transplant recipients compared to those receiving organs from deceased donors.Despite this trend,the overall result for changes in EF was not statistically significant(P=0.15).Additionally,the combined HR from the meta-analysis was 2.87(95%CI:1.76-4.69),suggesting that KTx significantly increases the likelihood of improved EF,though variability between studies persisted(I²=63%).CONCLUSION While KTx offers some promise for improving EF in male ESRD patients,the overall evidence remains inconclusive due to high heterogeneity between studies and a lack of statistical significance in the combined results.Despite this,individual studies suggest that KTx may lead to significant improvements in EF for certain subgroups,particularly living-donor recipients.Future research should focus on larger,well-designed cohort studies with standardized outcome measures to provide more definitive conclusions.Addressing SexDys as part of routine care for ESRD patients undergoing KTx is crucial to improving their overall quality of life.However,adjunct therapies such as phosphodiesterase type 5 inhibitors may be necessary for those who do not experience adequate improvements post-transplantation.
文摘Lin et al’s investigation on the association of activin A receptor type 1C(ACVR1C)(transforming growth factor beta type I receptor)single nucleotide poly-morphisms(SNPs)with esophageal squamous cell carcinoma(ESCC)risk in the Chinese population is a scientific approach.This study explores the susceptibility of ACVR1C polymorphism towards ESCC in the Chinese population,highlighting the polymorphism’s potentiality as an early diagnostic and therapeutic target.The author assessed about a thousand ESCC Chinese patients’samples for ACVR1C SNPs in a hospital-based cohort study using the ligation detection reaction method.Further,the hypothesis was tested using appropriate statistical genetic models and stratified analysis.ACVR1C SNPs can help assess ESCC susceptibility stratification and provide valuable information for individual diagnosis and treatment of ESCC patients.In order to account for confounding variables,find genuine SNP-disease relationships,boost statistical power,and make biological interpretation easier,it is imperative that genetic association studies of ESCC incorporate pertinent clinical aspects.
文摘The investigation by Zhu et al on the assessment of cellular proliferation markers to assist clinical decision-making in patients with hepatocellular carcinoma(HCC)using a machine learning model-based approach is a scientific approach.This study looked into the possibilities of using a Ki-67(a marker for cell proliferation)expression-based machine learning model to help doctors make decisions about treatment options for patients with HCC before surgery.The study used reconstructed tomography images of 164 patients with confirmed HCC from the intratumoral and peritumoral regions.The features were chosen using various statistical methods,including least absolute shrinkage and selection operator regression.Also,a nomogram was made using Radscore and clinical risk factors.It was tested for its ability to predict receiver operating characteristic curves and calibration curves,and its clinical benefits were found using decision curve analysis.The calibration curve demonstrated excellent consistency between predicted and actual probability,and the decision curve confirmed its clinical benefit.The proposed model is helpful for treating patients with HCC because the predicted and actual probabilities are very close to each other,as shown by the decision curve analysis.Further prospective studies are required,incorporating a multicenter and large sample size design,additional relevant exclusion criteria,information on tumors(size,number,and grade),and cancer stage to strengthen the clinical benefit in patients with HCC.
文摘Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.
文摘Insulin,a small protein with 51 amino acids synthesized by pancreatic β-cells,is crucial to sustain glucose homeostasis at biochemical and molecular levels.Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis.One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus(DM)(type 1,type 2,and gestational).Insulin resistance(IR)is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions.Metabolic syndrome(MS)is another pathophysiological condition that is associated with IR,hypertension,and obesity.Further,several other pathophysiological disorders/diseases are associated with the insulin malfunctioning,which include polycystic ovary syndrome,neuronal disorders,and cancer.Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms.Literature revealed that different biochemical events,molecular signaling pathways,microRNAs,and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM,insuloma,neurological disorder,MS,and cancer.In this review,we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.
文摘Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate cancer.Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer(CRPC).Present research establishes that prostate cancer stem-like cells(CSCs)play a central role in the development of treatment resistance followed by disease progression.Prostate CSCs are capable of self-renewal,differentiation,and regenerating tumor heterogeneity.The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants,epigenetic and genetic modifications leading to alteration in the tumor microenvironment,changes in ATP-binding cassette(ABC)transporters,and adaptations in molecular signaling pathways.ADT reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1(ALDH1A1),Prominin 1(PROM1/CD133),Indian blood group(CD44),SRY-Box Transcription Factor 2(Sox2),POU Class 5 Homeobox 1(POU5F1/Oct4),Nanog and ABC transporters.These markers indicate enhanced self-renewal and stemness stimulating CRPC evolution,metastatic colonization,and resistance to antiandrogens.In this review,we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC,their isolation,identification and characterization,as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities.
基金Efforts are supported by the Department of Defense Grants(W81XWH-18-1-0618,W81XWH-15-1-0558)VA Merit Review(1I01BX002494)to Gupta S.Kushwaha PP acknowledges financial support from University Grants Commission,India in the form of CSIR-UGC Senior Research fellowshipKumar S acknowledges Department of Science and Technology,India,and University Grants Commission,India for providing financial support in the form of DST-SERB Grant[EEQ/2016/000350]and UGC-BSR Research Start-Up-Grant[No.F.30-372/2017(BSR)]respectively.
文摘Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer treatment.Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct mechanisms and pathways.Understanding the molecular mechanisms involved in drug resistance remains an important area of research for identification of precise targets and drug discovery to improve therapeutic outcomes.This review highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.
基金support from the Indian Council of Medical Research(ICMR),India in the form of ICMR Senior Research fellowship.SK acknowledges the University Grants Commission(UGC),India and Department of Science and Technology(DST),India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[No.F.30-372/2017(BSR)]and DST-SERB Grant(EEQ/2016/000350)respectively.SK also acknowledges DST,India for providing the Departmental DST-FIST grant to the Department of Biochemistry,Central University of Punjab,India.AKS and MS acknowledges CSIR and ICMR,India funding agencies respectively for providing financial assistance in the form of a Senior Research Fellowship.KSP acknowledge DBT,India funding agencies for providing financial assistance in the form of Junior Research Fellowship.
文摘Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.
基金Efforts are supported by the Department of Defense Grant(W81XWH-18-1-0618 and W81XWH-19-1-0720)to Gupta S.Kushwaha PP acknowledges financial support from University Grants Commission,India in the form of CSIR-UGC Senior Research fellowshipKumar S acknowledges University Grants Commission,India+2 种基金Department of Science and Technology,India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[F.30-372/2017(BSR)]DST-SERB Grant(EEQ/2016/000350)respectively.Kumar S acknowledges Central University of Punjab,Bathinda,India for providing Research Seed Money Grant(GP-25)Singh AK,Prajapati KS,and Shuaib M acknowledge CSIR-India,DBT-India and DST-India funding agencies respectively for providing financial assistance in the form of Junior Research Fellowship.
文摘Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling pathways.In this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC emergence.Evolving knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.
基金supported by the Department of Defense Grants W81XWH-18-1-0618 and W81XWH-19-1-0720 and VA Merit Review 1I01BX002494 to Gupta S.Kumar S acknowledges University Grants Commission,India and Department of Science and Technology,India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[No.F.30-372/2017(BSR)]and DST-SERB Grant[EEQ/2016/000350].Kumar S acknowledges Central University of Punjab,Bathinda,India for providing Research Seed Money Grant[GP-25].
文摘Epidemiological studies suggest a close association between diet and cancer initiation,which provides evidence that the dietary components may be effectively developed as chemopreventive agents[1].These pieces of evidence are further supported by several case-control and cohort studies,which overwhelmingly support a converse association between the intake of phytochemicals and cancer risk[2,3].A number of clinical studies have been conducted demonstrating that dietary phytochemicals have the ability to inhibit tumorigenesis[4].Components presenting in fruit and vegetables termed“bioactive”phytochemicals belong to several classes of micronutrients,including flavonoids,polyphenols,and dietary fiber.These components have the ability to reduce the cancer risk alone or by interactions between them.
