Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when th...The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when the cations are the same and the anions are different,in complex 1,Na^(+)closes one port of CyB5Q[5]through Na—O seven coordination bonds to form a molecular bowl;in complex 3,Na^(+)completely closes the two ports of CyB5Q[5]to form a molecular capsule with six Na—O coordination bonds;in complexes 2 and 4,the two ports of CyB5Q[5]are completely closed to form K—O coordinated molecular capsules,but the K^(+)of complex 2 is six-coordinated and that of complex 4 is eight-/nine-coordinated.and complex 4 are connected by three oxygen bridges to form a 1D molecular chain.CCDC:2457122,1;2457121,2;2457400,3;2457120,4.展开更多
Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling ...Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.展开更多
Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study...Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study introduces a novel Fuzzy Nonlinear Additive Regression(FNAR)model to predict monthly GWL in an unconfined aquifer in eastern Iran,using a 19-year(1998–2017)dataset from 11 piezometric wells.Under three distinct scenarios with progressively increasing input complexity,the study utilized readily available climate data,including Precipitation(Prc),Temperature(Tave),Relative Humidity(RH),and Evapotranspiration(ETo).The dataset was split into training(70%)and validation(30%)subsets.Results showed that among three input scenarios,Scenario 3(Sc3,incorporating all four variables)achieved the best predictive performance,with RMSE ranging from 0.305 m to 0.768 m,MAE from 0.203 m to 0.522 m,NSE from 0.661 to 0.980,and PBIAS from 0.771%to 0.981%,indicating low bias and high reliability.However,Sc2(excluding ETo)with RMSE ranging from 0.4226 m to 0.9909 m,MAE from 0.3418 m to 0.8173 m,NSE from 0.2831 to 0.9674,and PBIAS from−0.598%to 0.968%across different months offers practical advantages in data-scarce settings.The FNAR model outperforms conventional Fuzzy Least Squares Regression(FLSR)and holds promise for GWL forecasting in data-scarce regions where physical or numerical models are impractical.Future research should focus on integrating FNAR with deep learning algorithms and real-time data assimilation expanding applications across diverse hydrogeological settings.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
BACKGROUND In an era leaning toward a personalized alignment of total knee arthroplasty,coronal plane alignment of the knee(CPAK)phenotypes for each population are studied;furthermore,other possible variables affectin...BACKGROUND In an era leaning toward a personalized alignment of total knee arthroplasty,coronal plane alignment of the knee(CPAK)phenotypes for each population are studied;furthermore,other possible variables affecting the alignment,such as ankle joint alignment,should be considered.AIM To determine CPAK distribution in the North African(Egyptian)population with knee osteoarthritis and to assess ankle joint line orientation(AJLO)adaptations across different CPAK types.METHODS A cross-sectional study was conducted on patients with primary knee osteoarthritis and normal ankle joints.Radiographic parameters included the mechanical lateral distal femoral angle,medial proximal tibial angle,and the derived calculations of joint line obliquity(JLO)and arithmetic hip-knee-ankle angle(aHKA).The tibial plafond horizontal angle(TPHA)was used for AJLO assessment,where 0°is neutral(type N),<0°is varus(type A),and>0°is valgus(type B).The nine CPAK types were further divided into 27 subtypes after incorporating the three AJLO types.RESULTS A total of 527 patients(1054 knees)were included for CPAK classification,and 435 patients(870 knees and ankles)for AJLO assessment.The mean age was 57.2±7.8 years,with 79.5%females.Most knees(76.4%)demonstrated varus alignment(mean aHKA was-5.51°±4.84°)and apex distal JLO(55.3%)(mean JLO was 176.43°±4.53°).CPAK types I(44.3%),IV(28.6%),and II(10%)were the most common.Regarding AJLO,70.2%of ankles exhibited varus orientation(mean TPHA was-5.21°±6.45°).The most frequent combined subtypes were CPAK type I-A(33.7%),IV-A(21.5%),and I-N(6.9%).A significant positive correlation was found between the TPHA and aHKA(r=0.40,P<0.001).CONCLUSION In this North African cohort,varus knee alignment with apex distal JLO and varus AJLO predominated.CPAK types I,IV,and II were the most common types,while subtypes I-A,IV-A,and I-N were commonly occurring after incorporating AJLO types;furthermore,the AJLO was significantly correlated to aHKA.展开更多
Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).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 Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have signi...Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular ana...BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular anastomosis to the recipient’s external iliac vein.These anatomical constraints can complicate graft implantation and increase the risk of postoperative complications.CASE SUMMARY To address the issue of short right renal veins,several surgical strategies have been proposed.In this report,we describe our experience with three cases in which venous extension was successfully achieved using a venous cuff interposition technique during back-table reconstruction.This approach was used to facilitate secure vascular anastomosis and improve graft positioning in anatomically complex transplant scenarios.CONCLUSION Venous cuff interposition represents an effective technique for managing short renal veins in living-donor kidney transplantation.It provides additional length and flexibility,easing anastomotic tension and supporting successful transplantation.展开更多
It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and er...It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and erythropoietic protoporphyria(EPP),which has not been previously documented.CASE SUMMARY We present a rare case of coexisting GS and EPP in a 23-year-old Chinese male with a long history of jaundice and recently found splenomegaly.Serial nonspecific hemolysis screening tests yielded inconsistent results,and investigations for common hemolytic etiologies were negative.However,Levitt’s carbon monoxide breath test,which measures erythrocyte lifespan(the gold-standard marker of hemolysis),demonstrated significant hemolysis,revealing a markedly shortened erythrocyte lifespan of 11 days(normal average 120 days).Genetic testing subsequently confirmed EPP with a homozygous ferrochelatase gene mutation and GS with a heterozygous uridine diphosphate glucuronosyl trans-ferase 1A1 gene mutation.CONCLUSION The rapid,non-invasive Levitt’s carbon monoxide breath test resolved the diagnostic challenge posed by a rare and complex cause of hyperbilirubinemia.展开更多
BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favo...BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favoured,reverse TSA(RTSA)is increasingly utilized.AIM To systematically compare the outcomes of RTSA and TSA in this specific patient population.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.Retrospective comparative studies evaluating RTSA and TSA in patients with GHOA and intact rotator cuff were included.Key outcomes assessed included complication and reoperation rates,patient-reported outcome measures(PROMs),and range of motion.Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool.RESULTS Twelve studies encompassing 1608 patients(580 RTSA,1028 TSA)met inclusion criteria.RTSA was associated with a lower reoperation rate compared to TSA[odds ratio=0.37;95%confidence interval(CI):0.14-0.94;P value=0.04],while no significant difference in overall complication rates was observed(odds ratio=0.47;95%CI:0.19-1.16;P value=0.10).RTSA patients showed superior outcomes in University of California Los Angeles,Simple Shoulder Test,and Shoulder Pain and Disability Index scores;however,the differences did not exceed the minimal clinically important difference.TSA patients had significantly better external rotation(mean difference=-9.0°;95%CI:-13.21 to-5.02;P value<0.0001).No significant differences were found in other range of motion measures or satisfaction scores.The overall methodological quality of included studies was moderate to serious.CONCLUSION In patients with GHOA and an intact rotator cuff,RTSA may offer comparable or improved outcomes to TSA with lower reoperation rates and similar complication profiles.Functional outcomes favour RTSA in certain patientreported outcome measures,while TSA retains an advantage in external rotation.Surgical decision-making should remain individualized based on patient characteristics and functional demands.展开更多
BACKGROUND Edwardsiella tarda(E.tarda)belongs to the family Enterobacteriaceae and is generally seen to cause infections mainly in fish,but is also capable of infecting humans.Extraintestinal infections occur in patie...BACKGROUND Edwardsiella tarda(E.tarda)belongs to the family Enterobacteriaceae and is generally seen to cause infections mainly in fish,but is also capable of infecting humans.Extraintestinal infections occur in patients with certain risk factors,including immunocompromised status.We recently diagnosed a case of spontaneous bacterial peritonitis(SBP)due to E.tarda in an immuno-compromised dialysis patient.CASE SUMMARY Patient was a 55-year-old male,with a history of diabetic nephropathy being treated with hemodialysis three times a week.He was referred to our hospital due to an increased volume of ascites,and blood examination revealed increased inflammatory reaction.At our emergency department,he developed fever,disturbance of consciousness,abdominal distension,and abdomen-wide pain.In addition,a dialysis shunt was confirmed in his right forearm,and the shunt site showed no signs of inflammation.No wounds were confirmed on or in his body.A blood examination revealed increased values of white blood cells,C-reactive protein,and creatinine.Plain chest and abdominal computed tomography scanning revealed increased ascites volume.Abdominal paracentesis was performed and a Gram stain revealed Gramnegative bacillus.These findings prompted diagnosis of SBP.The patient was admitted and treated with cefmetazole,causing fever resolution and symptom improvements.Later,E.tarda was identified in ascites culture.The patient improved with decreased inflammatory response and was discharged on the 12th day of hospitalization.The antibiotic was terminated after 14 days of treatment.SBP in this case may have developed from chronic renal failure and diabetes mellitus.CONCLUSION We report the first known case of SBP due to E.tarda in an immuno-compromised dialysis patient.展开更多
Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer fro...Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.展开更多
Objective:To compare the effectiveness,safety,acceptability,and confounding factors of the two-rod levonorgestrel implants between the Indoplant and Sinoplant implant brands.Methods:The study was a double-blind,random...Objective:To compare the effectiveness,safety,acceptability,and confounding factors of the two-rod levonorgestrel implants between the Indoplant and Sinoplant implant brands.Methods:The study was a double-blind,randomized controlled trial at three different centers in Indonesia.A total of 531 participants that met inclusion and exclusion criteria were randomized into two groups,with 264 participants in the Sinoplant group and 267 participants in the Indoplant group.At each center,participants were divided into two groups for Sinoplant and Indoplant.The participants were followed up for 36 months.Four parameters were evaluated:implant effectiveness,safety,acceptability,and confounding factors.Results:A total of 531 eligible participants were enrolled in this study.Both Sinoplant and Indoplant showed 100%efficacy in preventing pregnancy,with no significant differences in side effects.24.22%of the Sinoplant group and 22.18%of the Indoplant group reported weight changes.8.60%of the Sinoplant group and 9.73%of the Indoplant group reported menstrual changes,and 1.17%of the both groups experienced intermenstrual bleeding.Implant acceptability was 96.61%,with 3.39%dropout rates.Confounding factors such as age,parity,and contraceptive history did not significantly differ between the two groups.Conclusions:Sinoplant and Indoplant did not differ significantly in contraceptive effectiveness,safety,acceptability,and confounding factors.展开更多
Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear....Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.展开更多
Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves ...Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves targeting superficial tumors in patients with macronodular cirrhosis and an irregular liver surface.In a minimally invasive setting,the lack of tactile feedback on the hepatic surface makes detecting subcapsular HCC with ultrasound alone challenging.ICG fusion images can mimic the tactile feedback of the hand and act as an ultrasound booster.ICG fluorescence can be used to evaluate tumor residues after minimally invasive thermal ablation.ICG fluorescence imaging can also be used to identify the grade of HCC early on and evaluate the microinvasive component.展开更多
Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in...Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.展开更多
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
文摘The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when the cations are the same and the anions are different,in complex 1,Na^(+)closes one port of CyB5Q[5]through Na—O seven coordination bonds to form a molecular bowl;in complex 3,Na^(+)completely closes the two ports of CyB5Q[5]to form a molecular capsule with six Na—O coordination bonds;in complexes 2 and 4,the two ports of CyB5Q[5]are completely closed to form K—O coordinated molecular capsules,but the K^(+)of complex 2 is six-coordinated and that of complex 4 is eight-/nine-coordinated.and complex 4 are connected by three oxygen bridges to form a 1D molecular chain.CCDC:2457122,1;2457121,2;2457400,3;2457120,4.
基金supported by the National Natural Science Foundation of China,No.82101115(to JY)the Wuhan University Independent Innovation Fund Youth Project,No.2042021kf0094(to JY).
文摘Tunneling nanotubes are crucial structures for cellular communication and are observed in a variety of cell types.Glial cells,the most abundant cells in the nervous system,play a vital role in intercellular signaling and can show abnormal activation under pathological conditions.Our bibliometric analysis indicated a substantial increase in research on tunneling nanotubes over the past two decades,highlighting their important role in cellular communication.This review focuses on the formation of tunneling nanotubes in various types of glial cells,including astrocytes,microglia,glioma cells,and Schwann cells,as well as their roles in cellular communication and cargo transport.We found that glial cells influence the stability of the neural system and play a role in nerve regeneration through tunneling nanotubes.Tunneling nanotubes facilitate the transmission and progression of diseases by transporting pathogens and harmful substances.However,they are also involved in alleviating cellular stress by removing toxins and delivering essential nutrients.Understanding the interactions between glial cells through tunneling nanotubes could provide valuable insights into the complex neural networks that govern brain function and responses to injury.
基金supported by the Iran National Science Foundation(INSF)the University of Birjand under grant number 4034771.
文摘Groundwater modeling remains challenging due to heterogeneity and complexity of aquifer systems,necessitating endeavors to quantify Groundwater Levels(GWL)dynamics to inform policymakers and hydrogeologists.This study introduces a novel Fuzzy Nonlinear Additive Regression(FNAR)model to predict monthly GWL in an unconfined aquifer in eastern Iran,using a 19-year(1998–2017)dataset from 11 piezometric wells.Under three distinct scenarios with progressively increasing input complexity,the study utilized readily available climate data,including Precipitation(Prc),Temperature(Tave),Relative Humidity(RH),and Evapotranspiration(ETo).The dataset was split into training(70%)and validation(30%)subsets.Results showed that among three input scenarios,Scenario 3(Sc3,incorporating all four variables)achieved the best predictive performance,with RMSE ranging from 0.305 m to 0.768 m,MAE from 0.203 m to 0.522 m,NSE from 0.661 to 0.980,and PBIAS from 0.771%to 0.981%,indicating low bias and high reliability.However,Sc2(excluding ETo)with RMSE ranging from 0.4226 m to 0.9909 m,MAE from 0.3418 m to 0.8173 m,NSE from 0.2831 to 0.9674,and PBIAS from−0.598%to 0.968%across different months offers practical advantages in data-scarce settings.The FNAR model outperforms conventional Fuzzy Least Squares Regression(FLSR)and holds promise for GWL forecasting in data-scarce regions where physical or numerical models are impractical.Future research should focus on integrating FNAR with deep learning algorithms and real-time data assimilation expanding applications across diverse hydrogeological settings.
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approved by Institutional Review Board of Faculty of Medicine in Assiut University,No.04-2024-300470.
文摘BACKGROUND In an era leaning toward a personalized alignment of total knee arthroplasty,coronal plane alignment of the knee(CPAK)phenotypes for each population are studied;furthermore,other possible variables affecting the alignment,such as ankle joint alignment,should be considered.AIM To determine CPAK distribution in the North African(Egyptian)population with knee osteoarthritis and to assess ankle joint line orientation(AJLO)adaptations across different CPAK types.METHODS A cross-sectional study was conducted on patients with primary knee osteoarthritis and normal ankle joints.Radiographic parameters included the mechanical lateral distal femoral angle,medial proximal tibial angle,and the derived calculations of joint line obliquity(JLO)and arithmetic hip-knee-ankle angle(aHKA).The tibial plafond horizontal angle(TPHA)was used for AJLO assessment,where 0°is neutral(type N),<0°is varus(type A),and>0°is valgus(type B).The nine CPAK types were further divided into 27 subtypes after incorporating the three AJLO types.RESULTS A total of 527 patients(1054 knees)were included for CPAK classification,and 435 patients(870 knees and ankles)for AJLO assessment.The mean age was 57.2±7.8 years,with 79.5%females.Most knees(76.4%)demonstrated varus alignment(mean aHKA was-5.51°±4.84°)and apex distal JLO(55.3%)(mean JLO was 176.43°±4.53°).CPAK types I(44.3%),IV(28.6%),and II(10%)were the most common.Regarding AJLO,70.2%of ankles exhibited varus orientation(mean TPHA was-5.21°±6.45°).The most frequent combined subtypes were CPAK type I-A(33.7%),IV-A(21.5%),and I-N(6.9%).A significant positive correlation was found between the TPHA and aHKA(r=0.40,P<0.001).CONCLUSION In this North African cohort,varus knee alignment with apex distal JLO and varus AJLO predominated.CPAK types I,IV,and II were the most common types,while subtypes I-A,IV-A,and I-N were commonly occurring after incorporating AJLO types;furthermore,the AJLO was significantly correlated to aHKA.
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
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.
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
文摘Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
文摘BACKGROUND With the increasing use of laparoscopic techniques in living-donor kidney transplantation,limitations in donor vessel length,particularly of the right renal vein,pose significant challenges for vascular anastomosis to the recipient’s external iliac vein.These anatomical constraints can complicate graft implantation and increase the risk of postoperative complications.CASE SUMMARY To address the issue of short right renal veins,several surgical strategies have been proposed.In this report,we describe our experience with three cases in which venous extension was successfully achieved using a venous cuff interposition technique during back-table reconstruction.This approach was used to facilitate secure vascular anastomosis and improve graft positioning in anatomically complex transplant scenarios.CONCLUSION Venous cuff interposition represents an effective technique for managing short renal veins in living-donor kidney transplantation.It provides additional length and flexibility,easing anastomotic tension and supporting successful transplantation.
文摘It is challenging to diagnose isolated hyperbilirubinemia with rare and complex etiologies under the constraints of traditional testing conditions.Herein,we present a rare case of coexisting Gilbert syndrome(GS)and erythropoietic protoporphyria(EPP),which has not been previously documented.CASE SUMMARY We present a rare case of coexisting GS and EPP in a 23-year-old Chinese male with a long history of jaundice and recently found splenomegaly.Serial nonspecific hemolysis screening tests yielded inconsistent results,and investigations for common hemolytic etiologies were negative.However,Levitt’s carbon monoxide breath test,which measures erythrocyte lifespan(the gold-standard marker of hemolysis),demonstrated significant hemolysis,revealing a markedly shortened erythrocyte lifespan of 11 days(normal average 120 days).Genetic testing subsequently confirmed EPP with a homozygous ferrochelatase gene mutation and GS with a heterozygous uridine diphosphate glucuronosyl trans-ferase 1A1 gene mutation.CONCLUSION The rapid,non-invasive Levitt’s carbon monoxide breath test resolved the diagnostic challenge posed by a rare and complex cause of hyperbilirubinemia.
文摘BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favoured,reverse TSA(RTSA)is increasingly utilized.AIM To systematically compare the outcomes of RTSA and TSA in this specific patient population.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.Retrospective comparative studies evaluating RTSA and TSA in patients with GHOA and intact rotator cuff were included.Key outcomes assessed included complication and reoperation rates,patient-reported outcome measures(PROMs),and range of motion.Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool.RESULTS Twelve studies encompassing 1608 patients(580 RTSA,1028 TSA)met inclusion criteria.RTSA was associated with a lower reoperation rate compared to TSA[odds ratio=0.37;95%confidence interval(CI):0.14-0.94;P value=0.04],while no significant difference in overall complication rates was observed(odds ratio=0.47;95%CI:0.19-1.16;P value=0.10).RTSA patients showed superior outcomes in University of California Los Angeles,Simple Shoulder Test,and Shoulder Pain and Disability Index scores;however,the differences did not exceed the minimal clinically important difference.TSA patients had significantly better external rotation(mean difference=-9.0°;95%CI:-13.21 to-5.02;P value<0.0001).No significant differences were found in other range of motion measures or satisfaction scores.The overall methodological quality of included studies was moderate to serious.CONCLUSION In patients with GHOA and an intact rotator cuff,RTSA may offer comparable or improved outcomes to TSA with lower reoperation rates and similar complication profiles.Functional outcomes favour RTSA in certain patientreported outcome measures,while TSA retains an advantage in external rotation.Surgical decision-making should remain individualized based on patient characteristics and functional demands.
文摘BACKGROUND Edwardsiella tarda(E.tarda)belongs to the family Enterobacteriaceae and is generally seen to cause infections mainly in fish,but is also capable of infecting humans.Extraintestinal infections occur in patients with certain risk factors,including immunocompromised status.We recently diagnosed a case of spontaneous bacterial peritonitis(SBP)due to E.tarda in an immuno-compromised dialysis patient.CASE SUMMARY Patient was a 55-year-old male,with a history of diabetic nephropathy being treated with hemodialysis three times a week.He was referred to our hospital due to an increased volume of ascites,and blood examination revealed increased inflammatory reaction.At our emergency department,he developed fever,disturbance of consciousness,abdominal distension,and abdomen-wide pain.In addition,a dialysis shunt was confirmed in his right forearm,and the shunt site showed no signs of inflammation.No wounds were confirmed on or in his body.A blood examination revealed increased values of white blood cells,C-reactive protein,and creatinine.Plain chest and abdominal computed tomography scanning revealed increased ascites volume.Abdominal paracentesis was performed and a Gram stain revealed Gramnegative bacillus.These findings prompted diagnosis of SBP.The patient was admitted and treated with cefmetazole,causing fever resolution and symptom improvements.Later,E.tarda was identified in ascites culture.The patient improved with decreased inflammatory response and was discharged on the 12th day of hospitalization.The antibiotic was terminated after 14 days of treatment.SBP in this case may have developed from chronic renal failure and diabetes mellitus.CONCLUSION We report the first known case of SBP due to E.tarda in an immuno-compromised dialysis patient.
文摘Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.
基金supported by PT.Catur Dakwah Crane Pharmacy,an Indonesian pharmaceutical company.The funding was granted through a mutual agreement between the research team and the company,under the coordination of the National Population and Family Planning Board(BKKBN Indonesia).The funder provided financial support only and had no role in the study design,data collection,analysis,interpretation of data,or the decision to submit the manuscript for publication.
文摘Objective:To compare the effectiveness,safety,acceptability,and confounding factors of the two-rod levonorgestrel implants between the Indoplant and Sinoplant implant brands.Methods:The study was a double-blind,randomized controlled trial at three different centers in Indonesia.A total of 531 participants that met inclusion and exclusion criteria were randomized into two groups,with 264 participants in the Sinoplant group and 267 participants in the Indoplant group.At each center,participants were divided into two groups for Sinoplant and Indoplant.The participants were followed up for 36 months.Four parameters were evaluated:implant effectiveness,safety,acceptability,and confounding factors.Results:A total of 531 eligible participants were enrolled in this study.Both Sinoplant and Indoplant showed 100%efficacy in preventing pregnancy,with no significant differences in side effects.24.22%of the Sinoplant group and 22.18%of the Indoplant group reported weight changes.8.60%of the Sinoplant group and 9.73%of the Indoplant group reported menstrual changes,and 1.17%of the both groups experienced intermenstrual bleeding.Implant acceptability was 96.61%,with 3.39%dropout rates.Confounding factors such as age,parity,and contraceptive history did not significantly differ between the two groups.Conclusions:Sinoplant and Indoplant did not differ significantly in contraceptive effectiveness,safety,acceptability,and confounding factors.
基金supported by National Natural Science Foundation of China(Grant No.81900873 to A.Q.)the Jiangsu Provincial Key Research and Development Programme-social development(Grant No.BE2023777 to W.Z.)+1 种基金the Key Medical Research Project of Jiangsu Commission of Health(Grant No.H2022185 to W.Z.)the Clinical Capacity Enhancement Project of Jiangsu Province Hospital(Grant No.JSPH-MB-2023-18 to W.Z.)。
文摘Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
文摘Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves targeting superficial tumors in patients with macronodular cirrhosis and an irregular liver surface.In a minimally invasive setting,the lack of tactile feedback on the hepatic surface makes detecting subcapsular HCC with ultrasound alone challenging.ICG fusion images can mimic the tactile feedback of the hand and act as an ultrasound booster.ICG fluorescence can be used to evaluate tumor residues after minimally invasive thermal ablation.ICG fluorescence imaging can also be used to identify the grade of HCC early on and evaluate the microinvasive component.
文摘Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.
