TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage.Notably,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal fibrosis.However,the regulatory impact of TRPC6 on renal fibrosis remains unclear.Methods In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham operation.Kidneys and serum were collected on days 7,14,21,and 28 after euthanasia.In vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 h.The anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western blotting.Results Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1.TRPC6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro.Additionally,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 deletion.Conclusion These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3βpathway.Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential

BACKGROUND Up until now,no research has been reported on the association between the cli-nical growth rate of multilocular cystic renal neoplasm of low malignant potential(MCRNLMP)and computed tomography(CT)imaging characteristics.Our study sought to examine the correlation between them,with the objective of distin-guishing unique features of MCRNLMP from renal cysts and exploring effective management strategies.AIM To investigate optimal management strategies of MCRNLMP.METHODS We retrospectively collected and analyzed data from 1520 patients,comprising 1444 with renal cysts and 76 with MCRNLMP,who underwent renal cyst decom-pression,radical nephrectomy,or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution.Detection of MC-RNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology.RESULTS Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP.Precisely,it comprises 1.48%of all cases involving simple renal cysts,5.26%of those with complex renal cysts,and a noteworthy 12.11%of renal tumors coexisting with renal cysts,indicating a statistically significant difference(P=0.001).Moreover,MCRNLMP constituted a significant 22.37%of the patient po-pulation whose cysts demonstrated a rapid growth rate of≥2.0 cm/year,whereas it only represented 0.66%among those with a growth rate below 2.0 cm/year.Of the 76 MCRNLMP cases studied,none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis.In the remaining 67 patients,who were actively monitored over a 3-year postoperative period,only one showed suspicious recurrence on CT scans.CONCLUSION MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators.In treating MCRNLMP,partial nephrectomy is preferred,while radical nephrectomy should be minimi-zed.After surgery,active monitoring is advisable to prevent unnecessary nephrectomy.

Autosomal Dominant Polycystic Kidney Disease: Epidemiological, Clinical Aspects and Predictive Factors of Poor Renal Prognosis (About 300 Cases)

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a common, multisystemic, and progressive hereditary disease. It accounts for 6 to 8% of incident cases of end-stage chronic renal disease (ESRD) in developed countries. The aim of this study is to describe the predictive factors for the development of end-stage chronic kidney disease (CKD) in the course of this disease. Material and Methods: This is a retrospective, descriptive, and analytical study including 300 cases of ADPKD collected at the Nephrology Department of Ibn-Sina Hospital in Rabat over a period of 30 years (1993 to 2023). Included in the study are all patients with ADPKD meeting the ultrasound diagnostic criteria. The analysis focused on demographic, clinical, paraclinical, evolutionary data, as well as prognostic factors associated with renal function deterioration. Results: The mean age of patients at diagnosis is 51.53 +/− 17 years [16 - 93] with a male predominance. The median serum creatinine at diagnosis is 15.5 mg/l [10 - 34]. 21% of patients had ESRD (eGFR 300 mg/24h (21%). The most common cystic complication is hemorrhage (12.3%). 21.3% of patients had hepatorenal polycystic disease. In adjusted analysis, the predictive risk factors for the occurrence of ESRD were smoking (p = 0.019), anemia (p Conclusion: ADPKD can progress insidiously to ESRD. Identification and early treatment of predictive factors for poor renal prognosis could contribute to a better outcome for this disease.

Surgical treatment of left-sided renal carcinoma with grade II inferior vena cava tumour thrombus: a report and review of the literature

The surgical removal of renal cancer,along with the thrombectomy of the inferior vena cava tumour thrombus,represents a remarkable milestone in urological surgery.This procedure is not only technically demanding but also requires a high level of surgical expertise.Managing renal cancer combined with a vena cava tumour thrombus poses significant challenges,especially when dealing with combined grade Ⅱ-Ⅳ inferior vena cava tumour thrombus.The complexity of these cases is further exacerbated by the delicate anatomical structures involved and the need to preserve critical vessels while effectively removing the tumour.The Upper Urethral Tumour Treatment Centre of Weifang People's Hospital successfully treated a challenging case of left renal tumour combined with grade II inferior vena cava tumour thrombus.The surgical team,led by experienced urological surgeons,meticulously planned and executed the procedure,ensuring minimal trauma to the patient and complete removal of the tumour.This achievement not only demonstrates the hospital's commitment to providing state-of-the-art surgical care but also highlights the importance of continued research and training in urological oncology.The successful outcome of this case is a testament to the expertise and dedication of the medical team and offers hope to patients facing similar complex surgical challenges.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

基于糖原合成酶激酶-3β及内质网应激探讨Renalase抗肾脏纤维化的作用机制

目的 探讨糖原合成酶激酶-3β(GSK-3β)在Renalase抗肾脏纤维化过程中的作用及其可能的机制。方法 选用C57BL/6小鼠,予以下分组:(1)Sham+Ad-β-gal组;(2)Sham+Ad-Renalase组;(3)UUO+Ad-β-gal组;(4)UUO+Ad-Renalas组。观察GSK-3β表达的变化,其中UUO组为单侧输尿管结扎致肾脏纤维化模型组,Sham组为假手术对照组,Ad-Renalase为过表达Renalase腺病毒,Ad-β-gal为对照腺病毒。然后应用病毒转染技术上调(UUO+Ad-Renalase+AAV-GSK-3β组)及下调(UUO+Ad-Renalase+Ad-GSK-3β-RNAi组)GSK-3β后观察Renalase抗纤维化作用的变化。结果 与假手术(Sham)组相比,UUO组GSK-3β表达增加;与UUO+Ad-β-gal组相比,UUO+Ad-Renalase组纤维组织沉积减少、纤维化标志蛋白Col-Ⅰ和FN表达下降的同时GSK-3β表达下调;当上调GSK-3β后,Renalase抗纤维化作用被抵消,而当下调GSK-3β后,与UUO+Ad-Renalase组相比,UUO+Ad-Renalase+Ad-GSK-3β-RNAi组纤维化没有进一步改善。同时观察到与Sham组相比,UUO组内质网应激激活明显,过表达Renalase后,内质网应激被抑制。当加入内质网应激激动剂TM后,与UUO+Ad-Renalase组相比,UUO+Ad-Renalase+TM组纤维化加重,GSK-3β表达升高;但无论GSK-3β升高或者降低,内质网应激均无明显变化。结论 本研究证实在单侧输尿管结扎致肾脏纤维化过程中,Renalase通过抑制内质网应激下调GSK-3β表达从而延缓肾脏纤维化。

Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia:A Prospective,Randomized,Open,Parallel Controlled and Multicenter Clinical Study

Objective This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia.Methods A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups.Patients in the control group were treated with polysaccharide-iron complex,and those in the experimental group were administered Jianpi Shengxue tablet.After 8 weeks of continuous treatment,the therapeutic outcomes regarding anemia were compared between the two groups.Results After treatment,the red blood cell(RBC)count,hematocrit(HCT),reticulocyte percentage(RET),ferritin(SF),serum iron(SI),transferrin saturation(TSAT),and serum albumin(ALB)all increased(P<0.01),and the clinical symptom score and total iron binding capacity decreased(P<0.01)in the experimental group.Moreover,the improvements in RBC,HCT,RET,SF,SI,TAST,ALB,and clinical symptoms(fatigue,anorexia,dull skin complexion,numbness of hands and feet)in the experimental group were significantly greater than those in the control group(P<0.05).The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group(P<0.01).Conclusion The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia,leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Development of a Decision Aid for Family Surrogate Decision Makers of Critically Ill Patients Requiring Renal Replacement Therapy in ICU:A User-Centered Design for Rapid Prototyping

Objectives Renal replacement therapy(RRT)is increasingly adopted for critically ill patients diagnosed with acute kidney injury,but the optimal time for initiation remains unclear and prognosis is uncertain,leading to medical complexity,ethical conflicts,and decision dilemmas in intensive care unit(ICU)settings.This study aimed to develop a decision aid(DA)for the family surrogate of critically ill patients to support their engagement in shared decision-making process with clinicians.Methods Development of DA employed a systematic process with user-centered design(UCD)principle,which included:(i)competitive analysis:searched,screened,and assessed the existing DAs to gather insights for design strategies,developmental techniques,and functionalities;(ii)user needs assessment:interviewed family surrogates in our hospital to explore target user group's decision-making experience and identify their unmet needs;(iii)evidence syntheses:integrate latest clinical evidence and pertinent information to inform the content development of DA.Results The competitive analysis included 16 relevant DAs,from which we derived valuable insights using existing resources.User decision needs were explored among a cohort of 15 family surrogates,revealing four thematic issues in decision-making,including stuck into dilemmas,sense of uncertainty,limited capacity,and delayed decision confirmation.A total of 27 articles were included for evidence syntheses.Relevant decision making knowledge on disease and treatment,as delineated in the literature sourced from decision support system or clinical guidelines,were formatted as the foundational knowledge base.Twenty-one items of evidence were extracted and integrated into the content panels of benefits and risks of RRT,possible outcomes,and reasons to choose.The DA was drafted into a web-based phototype using the elements of UCD.This platform could guide users in their preparation of decision-making through a sequential four-step process:identifying treatment options,weighing the benefits and risks,clarifying personal preferences and values,and formulating a schedule for formal shared decision-making with clinicians.Conclusions We developed a rapid prototype of DA tailored for family surrogate decision makers of critically ill patients in need of RRT in ICU setting.Future studies are needed to evaluate its usability,feasibility,and clinical effects of this intervention.

Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient:A case repor

BACKGROUND Ewing’s sarcoma(ES)is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young adults.Primary renal ES is rare;only a few cases and a small case series have been documented,and only four cases involved primary renal ES in older people(>65 years old).CASE SUMMARY Herein,we describe the radiological and pathological features of primary renal ES in an older person.A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed tomography.Ultrasound-guided biopsy revealed that the tumor contained small round blue cells.The patient underwent a right radical nephrectomy.The tumor cells showed diffuse membranous CD99,and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox 2.Fluorescence in situ hybridization revealed EWSR1 translocation.Postoperatively,18F-fluorodeoxyglucose positron emission tomography revealed no evidence of metastasis.The patient was diagnosed with primary renal ES.Six months following the surgery,local recurrence and distant metastasis were observed.Primary renal ES is rare and often lethal in older individuals.The specific imaging findings are unknown,and treatment protocols have not been standardized.CONCLUSION This case report describes the radiological and pathological features of primary renal ES in an older person.

Efficacy and safety of Nafamostat mesylate in patients with endstage renal failure

BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.

Three cancers in the renal pelvis,bladder,and colon:A case report

BACKGROUND Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development.It is particularly rare for an individual to have more than two primary cancers.In this report,we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis,bladder,and colon.CASE SUMMARY On December 30,2014,a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week.A computed tomography(CT)scan revealed wall thickening in the left ureter’s upper segment,while a CT urography revealed a left renal pelvis tumor.A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015.The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis.The final pathological tumor stage was pT1N0M0.After surgery,this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin,as well as bladder infusion therapy with gemcitabine.On December 18,2017,the patient was admitted once again to our hospital with a one-day history of painless gross hematuria.A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder.Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29,2017.The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder(maximum size 3.7 cm×2.6 cm).The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery.The pathological tumor stage was pT1N0M1.The patient refused chemotherapy after surgery.After another six years,the patient returned on February 28,2023,complaining of periumbilical pain that had lasted six days.This time,a CT scan of the abdomen showed a tumor in the ascending colon,but a subsequent colonoscopy examination indicated a tumor in the descending colon.On March 12,2023,a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia.Postoperative pathological findings revealed that all three tumors were adenocarcinomas.The final pathological tumor stage was pT3N0M0.The patient had an uneventful postoperative recovery and was discharged without complications.CONCLUSION The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon.Bladder cancer is considered a metastasis of renal pelvis cancer after surgery.Optimal treatment can be implemented by evaluating the patient’s histological features,clinical history,and tumor distribution correctly.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.

Crossed renal ectopia with rectal cancer:A case report

BACKGROUND Crossed renal ectopia(CRE)occurs when one kidney crosses the midline from the primary side to the contralateral side while the ureter remains on the primary side.Rectal cancer,one of the most common malignant tumors of the digestive tract,refers to cancer from the dentate line to the rectosigmoid junction.The concurrent presentation of CRE alongside rectal cancer is an uncommon clinical observation.CASE SUMMARY Herein,we report a 69-year-old male patient with rectal cancer who was diagnosed with CRE via computed tomography during hospitalization.Following thorough preoperative evaluations,the patient underwent Dixon surgery.CONCLUSION We performed laparoscopic radical resection of rectal cancer and adequate lymph node removal in a patient with CRE with no postoperative discomfort.