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.

High Urine Retention: Experience in a Series of Patients with Renal Failure Patients

Purpose: High urinary retention (HUR) can negatively impact renal function. Our study aimed to present the epidemiological, diagnostic, and therapeutic aspects of HUR in a Senegalese academic hospital. Patients and Methods: We conducted a retrospective study of 70 patients with HUR associated with renal failure from January 2017 to December 2020. Parameters examined included: age, sex, coexisting conditions affecting renal function, clinical symptoms, diagnostic tests, causes of HUR, urinary diversion, and patient outcomes. Results: The average age was 66, with a majority of male patients (87%). Twenty-three patients had pre-existing medical conditions. Oligo-anuria was the most common reason for detecting HUR (70%). Half of the patients had an ECOG score ≥ 2. The mean creatinine level was 50.7 mg/l. Nineteen patients exhibited hydroelectrolytic disorders. Bacterial colonization was observed in 25 patients. Ultrasound and computed tomography were the most frequently performed imaging tests (100% and 62.8%, respectively). Sixty-seven patients had ureterohydronephrosis (UHN), with bilateral UHN in 88.6% of cases. Pelvic cancers (47.1%) were the primary cause of HUR, primarily bladder cancers (27.1%). Nephrostomy was the most common urinary drainage method (50%), particularly for obstructions due to pelvic cancer (88.6%). The majority of patients (52.8%) regained normal renal function after drainage. Nineteen deaths occurred among elderly patients with compromised general health. Conclusion: Urinary drainage significantly improved renal function for most patients. Pelvic cancer emerged as the leading cause of HUR. Nephrostomy was the predominant drainage method.

Learning Discriminatory Information for Object Detection on Urine Sediment Image

In clinical practice,the microscopic examination of urine sediment is considered an important in vitro examination with many broad applications.Measuring the amount of each type of urine sediment allows for screening,diagnosis and evaluation of kidney and urinary tract disease,providing insight into the specific type and severity.However,manual urine sediment examination is labor-intensive,time-consuming,and subjective.Traditional machine learning based object detection methods require hand-crafted features for localization and classification,which have poor generalization capabilities and are difficult to quickly and accurately detect the number of urine sediments.Deep learning based object detection methods have the potential to address the challenges mentioned above,but these methods require access to large urine sediment image datasets.Unfortunately,only a limited number of publicly available urine sediment datasets are currently available.To alleviate the lack of urine sediment datasets in medical image analysis,we propose a new dataset named UriSed2K,which contains 2465 high-quality images annotated with expert guidance.Two main challenges are associated with our dataset:a large number of small objects and the occlusion between these small objects.Our manuscript focuses on applying deep learning object detection methods to the urine sediment dataset and addressing the challenges presented by this dataset.Specifically,our goal is to improve the accuracy and efficiency of the detection algorithm and,in doing so,provide medical professionals with an automatic detector that saves time and effort.We propose an improved lightweight one-stage object detection algorithm called Discriminatory-YOLO.The proposed algorithm comprises a local context attention module and a global background suppression module,which aid the detector in distinguishing urine sediment features in the image.The local context attention module captures context information beyond the object region,while the global background suppression module emphasizes objects in uninformative backgrounds.We comprehensively evaluate our method on the UriSed2K dataset,which includes seven categories of urine sediments,such as erythrocytes(red blood cells),leukocytes(white blood cells),epithelial cells,crystals,mycetes,broken erythrocytes,and broken leukocytes,achieving the best average precision(AP)of 95.3%while taking only 10 ms per image.The source code and dataset are available at https://github.com/binghuiwu98/discriminatoryyolov5.

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite identification.However,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples.The experimental CCS values,along with mass spectral properties,were reported for the 174 metabolites.The experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS values.Among the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of VLMs.The TWCCSN2 values were highly repeatable,with inter-day variations of<1%relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(DCCS)within±2%of the reported drift tube IMS(DTIMS)and TWIMS CCS values.The complexity of the urine matrix did not affect the precision of the method,as evidenced by DCCS within±1.92%.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of 1.Among these 55 metabolites,53(96%)were VLMs.The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

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.

Renal resistive index measurements by ultrasound in patients with liver cirrhosis:Magnitude and associations with renal dysfunction

BACKGROUND The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction,ultimately causing acute kidney injury(AKI).The renal resistive index(RRI)is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance.AIM To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI.METHODS This was a prospective observational study,where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis.The association of RRI with AKI was studied.The receiver operating characteristic(ROC)curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes.Multivariate analysis was conducted to determine the predictors of high RRI.RESULTS The mean patient age was 49.08±11.68 years,with the majority(79.5%)being male;the predominant etiology of cirrhosis was alcohol(39%).The mean RRI for the study cohort was 0.68±0.09,showing a progressive increase with higher Child-Pugh class of cirrhosis.Overall,AKI was present in 129(64.5%)patients.The mean RRI was significantly higher in patients with AKI compared to those without it(0.72±0.06 vs 0.60±0.08;P<0.001).A total of 82 patients(41%)had hepatorenal syndrome(HRS)-AKI,29(22.4%)had prerenal AKI(PRA),and 18(13.9%)had acute tubular necrosis(ATN)-AKI.The mean RRI was significantly higher in the ATN-AKI(0.80±0.02)and HRS-AKI(0.73±0.03)groups than in the PRA(0.63±0.07)and non-AKI(0.60±0.07)groups.RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI(area under ROC curve:93.9%).AKI emerged as an independent predictor of high RRI(adjusted odds ratio[OR]:11.52),and high RRI independently predicted mortality among AKI patients(adjusted OR:3.18).CONCLUSION In cirrhosis patients,RRI exhibited a significant association with AKI,effectively differentiated between AKI phenotypes,and predicted AKI mortality.

Ipsilateral retroperitoneal papillary renal cell carcinoma 27 years after simple nephrectomy for a renal abscess:A case report

BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the native kidney has rarely been reported.To our knowledge,this is the first reported case of RCC developing in the ipsilateral retroperitoneal space after a simple nephrectomy(SN)for inflammatory renal disease.CASE SUMMARY A 63-year-old woman was referred to our hospital following the incidental discovery of a left retroperitoneal mass without specific symptoms.Her medical history revealed a left SN 27 years ago due to a renal abscess.Magnetic resonance imaging of the abdomen revealed three oval masses in the left retroperitoneum.The masses were successfully excised,and subsequent pathology confirmed papillary RCC.After surgery,the patient remained disease-free for 11 years without adjuvant therapy.CONCLUSION Clinicians should be vigilant of RCC in patients with retroperitoneal masses,especially after SN for inflammatory renal disease.

Effects of Inhabiting and Life Patterns on the UV Spectral Properties of Small Mammalian Herbivores’ Urine

It is well known that avian predators can use prey excretions such as urine and feces to track their prey, and the urine and feces of small mammalian herbivores can reflect ultraviolet (UV) light and emit fluorescent light. There are still some debates as to whether UV visibility of small mammalian herbivores’ urine is used as a hunting cue by avian raptors. Some studies in Europe have demonstrated that diurnal raptors are capable of utilizing these cues to target key prey species. However, researchers in Australia have argued that raptors do not use the UV visibility of urine while hunting. To our knowledge, there are no reports from Asia concerning the ultraviolet spectral characteristics of small mammal herbivores’ urine. This study examined the UV spectral properties of urine from 6 small mammal herbivores species by comparing the UV reflectance and fluorescence spectra of urine from small mammalian herbivores living in plateau meadows, plateau shrubs, open marshland, farmland, and semi-desert grassland in China. In addition, we compared the UV spectral properties of urine from ground-dwelling species of rodents and subterranean species to determine whether ultraviolet visibility of small mammal herbivores’ urine could be used as a visual signal by Asian vole-eating raptors. The results showed that: 1) the SC370 values of urine from four small mammal herbivores species were ordered as plateau pika (plateau meadow) > root voles (plateau bush) > reed voles (swampland) > Brandt’s vole (desert grassland);and 2) UV fluorescence peak intensity and the wavelengths of urine from ground-dwelling species (such as the root vole, plateau pika, or Brandt’s vole) were significantly higher than those of subterranean-dwelling species (mandarin vole and plateau zokor). These results indicate that UV visibility of small mammal herbivores’ urine may act as a visual cue for raptors.

Can the Urine Dipstick Test Be an Alternative in the Screening of Urinary Tract Infections for Inpatients in the Context of a Low-Income Country?

Background: Urinary Tract Infection (UTI), a prevalent bacterial infection in adults, heavily relies on cytobacteriological examination of urine (CBEU) for diagnosis. However, in resource-limited countries, accessibility to CBEU remains hindered by cost and availability. This study aims to assess the utility of the Urinary Dipstick Test (UDT) in diagnosing UTIs among hospitalized patients in the context of limited resources. Methods: A cross-sectional study was conducted from February to May 2019, encompassing hospitalized patients who underwent CBEU at the bacteriology unit of Sour? Sanou University Hospital. UDT and CBEU were concurrently performed, and UDT’s analytical and diagnostic performance was evaluated against CBEU, considered the gold standard. Results: A total of 274 CBEU requests were registered, involving 274 patients (159 males) with a mean age of 45.8 ± 21.3 years (ranging from 1 to 90 years). UTI was confirmed in 90 patients, yielding a frequency of 32.85%. The UTI bacteriological profile was dominated by Enterobacteriaceae (75.23%), primarily Escherichia coli (60.55%). Nitrite and Leukocytes were positive in 54 (19.8%) and 157 (53.6%) of the samples tested. Among patients with confirmed UTI, Nitrite, and Leukocytes were positive in 30 (33%) and 71 (79%) patients respectively. UDT demonstrated variable performance based on nitrite and leukocyte combination: Sensitivity (57%-82%), Specificity (7%-98%), Positive Predictive Value (PPV) (43%-57%), Negative Predictive Value (NPV) (43%-67%). UDT performed slightly better in women (NPV = 88%) and inpatients without urinary catheters (NPV = 75% and PPV = 80%). Conclusion: This study underscores UDT’s potential utility in excluding UTIs among women, younger patients, and inpatients without urinary catheters, albeit with limited confidence. The UDT emerges as a complementary tool for UTI screening, particularly in resource-limited settings.

A pilot clinical study of developing an External Assist Targeting Device for rapid and precise renal calyx access during percutaneous nephrolithotomy

Objective:To design a device to increase the accuracy of the targeting process and reduce the radiation exposure to both the patients and the medical staff.Methods:We analyzed the inherent problem and designed the External Assist Targeting Device(EATD)to assist in the alignment of needle targeting on the desired renal calyx under fluoroscopic guidance.The EATD was designed to allow rapid and precise access to calyces at all angles,with a simple two-step puncture protocol developed for puncturing a target renal calyx.We then tested the device in a pilot human trial with four patients.Results:In experiments with phantom models,the time for successful targeting was reduced by 31%using the device.The mean fluoroscopic time was reduced by 40%.In initial human trial,the puncture time was shortened by 66%and the radiation dose was decreased by 65%compared to free-hand technique.No complication was observed during the trial.Conclusion:The EATD was found to be cost effective,portable,simple to set up,and safe to operate for assisting in the percutaneous nephrolithotomy procedures.Our preliminary tests showed high degree of accuracy in gaining precise access to a targeted renal calyx with much shorter time and lesser radiation dose.The EATD also has the potential to be used to access other organs with precision under fluoroscopic guidance.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

Diagnosis of an intermediate case of maple syrup urine disease:A case report

BACKGROUND Maple syrup urine disease(MSUD)is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids(BCAAs).However,the clinical and metabolic screening is limited in identifying all MSUD patients,especially those patients with mild phenotypes or are asymptomatic.This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis.CASE SUMMARY This study reports the diagnostic process of a boy with intermediate MSUD.The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age.Preliminary clinical and metabolic profiling did not support a specific disease.However,whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene,confirming the proband as having MSUD with non-classic mild phenotypes.His clinical and laboratory data were retrospectively analyzed.According to his disease course,he was classified into an intermediate form of MSUD.His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD.In addition,genetic counseling and prenatal diagnosis were provided to his parents.CONCLUSION Our work provides diagnostic experience of an intermediate MSUD case,suggesting that a genetic analysis is important for ambiguous cases,and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.

Incomplete distal renal tubular acidosis uncovered during pregnancy:A case report

BACKGROUND Renal tubular acidosis(RTA)is a renal cause of non-anion-gap metabolic acidosis characterized by low urinary ammonia excretion.This condition has a low prevalence,and various congenital and acquired etiologies.To date,only a few cases of idiopathic RTA uncovered during pregnancy have been reported.CASE SUMMARY A previously healthy 32-year-old Korean woman at 30 wk of gestation was admitted to Pusan National University Hospital with preterm labor.At admission,the patient presented with hypokalemia,non-anion-gap metabolic acidosis,and nephrocalcinosis.Distal RTA was diagnosed based on laboratory blood and urine findings and imaging examinations.Various tests,including next-generation gene sequencing panels for nephropathy,were performed to determine the etiology of the disease,which indicated that it was idiopathic.The patient received sodium bicarbonate and potassium chloride supplementation.After 3 wk,she delivered a baby who was subsequently diagnosed with corpus callosum agenesis and colpocephaly.During regular follow-ups for 6 mo postpartum,her hypokalemia and metabolic acidosis were gradually resolved,and medications eventually discontinued.CONCLUSION Herein we describe a case of idiopathic distal RTA discovered during pregnancy.Hypokalemia and metabolic acidosis resolved spontaneously after delivery.

Urine Cystatin C Determination in the Establishment of Reference Interval in the Diagnosis and Treatment of Renal Injury

Objective: To establish the diagnostic concentration range of urine cystatin C and the control level of urine cystatin C for patients with renal injury, and to help promote the establishment of standardization of urine cystatin C detection. Methods: 150 urine specimens and blood specimens from kidney injury patients and healthy people were collected, and stored in the refrigerator at -80°C for later use. After the specimens were collected, they were uniformly tested. Comparing the difference of blood and urine cystatin C between the kidney injury group and the healthy control group, the application value of urine cystatin C in the diagnosis and treatment of kidney injury was put forward. Results: The concentrations of cystatin C in urine and blood of renal injury group were 1.04 ± 2.14 mg/L and 1.94 ± 2.36 mg/L respectively;the concentrations of cystatin C in urine and blood of healthy control group were 0.11 ± 0.05 mg/L and 0.83 ± 0.20 mg/L respectively. The urine and blood cystatin C of the kidney injury group were significantly higher than those of the healthy control group. Compared the results of the two groups, the t values were 5.3210 and 5.7399, respectively. The P value is 0.0000;the difference is statistically significant;in comparison of urine and blood cystatin C in the kidney injury group, the value is that t = 3.4600, P = 0.0003;in comparison of urine and blood cystatin C in the healthy control group, the value is that t = 42.7744, P = 0.0000. By investigating the urine cystatin C concentration of patients with kidney injury, whether it is kidney injury or healthy controls, urine cystatin C is significantly lower than blood cystatin C. Conclusion: According to the results of this study, the concentration of urinary cystatin C in the healthy control group is 0.11 ± 0.05 mg/L. The reference interval of urinary cystatin C proposed in this study is 0.06 - 0.16 mg/L, which can be established by comprehensive multi center research. Through a multi-center study of the baseline level of urinary cystatin C in patients with renal injury, the diagnostic concentration interval of urinary cystatin C and the control level of urine cystatin C for renal injury patients were established.

Diagnostic value of matrix metalloproteinases 2, 7 and 9 in urine for early detection of colorectal cancer

BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9 in urine for CRC.METHODS Of 59 healthy controls,47 patients with colon polyps and 82 patients with CRC were included in this study.Carcinoembryonic antigen(CEA)in serum and MMP2,MMP7,and MMP9 in urine were detected.The combined diagnostic model of the indicators was established by binary logistic regression.The receiver operating characteristic curve(ROC)of the subjects was used to evaluate the independent and combined diagnostic value of the indicators.RESULTS The MMP2,MMP7,MMP9,and CEA levels in the CRC group differed significantly from levels in the healthy controls(P<0.05).The levels of MMP7,MMP9,and CEA also differed significantly between the CRC group and the colon polyps group(P<0.05).The area under the curve(AUC)distinguishing between the healthy control and the CRC patients using the joint model with CEA,MMP2,MMP7 and MMP9 was 0.977,and the sensitivity and specificity were 95.10%and 91.50%,respectively.For early-stage CRC,the AUC was 0.975,and the sensitivity and specificity were 94.30%and 98.30%,respectively.For advanced stage CRC,the AUC was 0.979,and the sensitivity and specificity were 95.70%and 91.50%,respectively.Using CEA,MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group,the AUC was 0.849,and the sensitivity and specificity were 84.10%and 70.20%,respectively.For early-stage CRC,the AUC was 0.818,and the sensitivity and specificity were 76.30%and 72.30%,respectively.For advanced stage CRC,the AUC was 0.875,and the sensitivity and specificity were 81.80%and 72.30%,respectively.CONCLUSION MMP2,MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.

Preliminary Application of WCX Magnetic Bead-Based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry in Analyzing the Urine of Renal Clear Cell Carcinoma

Objective To evaluate the application of weak cation exchange (WCX) magnetic bead-based Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in detecting differentially expressed proteins in the urine of renal clear cell carcinoma (RCCC) and its value in the early diagnosis of RCCC.Methods Eleven newly diagnosed patients (10 males and 1 female, aged 46-78, mean 63 years) of renal clear cell carcinoma by biopsy and 10 healthy volunteers (all males, aged 25-32, mean 29.7 years) were enrolled in this study. Urine samples of the RCCC patients and healthy controls were collected in the morning.Weak cation exchange (WCX) bead-based MALDI-TOF MS technique was applied in detecting differential protein peaks in the urine of RCCC. ClinProTools2.2 software was utilized to determine the characteristic proteins in the urine of RCCC patients for the predictive model of RCCC.Results The technique identified 160 protein peaks in the urine that were different between RCCC patients and health controls; and among them, there was one peak (molecular weight of 2221.71 Da) with statistical significance (P=0.0304). With genetic algorithms and the support vector machine, we screened out 13 characteristic protein peaks for the predictive model.Conclusions The application of WCX magnetic bead-based MALDI-TOF MS in detecting differentiallyexpressed proteins in urine may have potential value for the early diagnosis of RCCC.

Multivariate Analysis of Female Stress Urinary Incontinence and Establishment of a Prediction Model

Stress urinary incontinence(SUI)is a symptom of uncontrolled urine outflow that affects millions of women worldwide[1].SUI is a significant healthcare issue that affects the quality of life of women across numerous domains,including social activities,physical health,mental well-being,employment,and sexual life.

Assessment of Renal Erythropoietic Status of the Newly Diagnosed Diabetic Patients without Renal Impairment in Benin City, Nigeria

Diabetes mellitus is a carbohydrate metabolism disorder which is caused due to impairment in insulin secretion and/or the activity of insulin, leading to chronic hyperglycemia with defective carbohydrate, fat and protein metabolism. This study aimed at assessing the erythropoietin (EPO), hemoglobin and renal parameters levels among the newly diagnosed diabetic patients and providing valuable insights into the management and progression of the disease. A case-control study was conducted on samples of 60 consenting participants including newly diagnosed diabetic patients (n − 30), and healthy controls (n − 30) of age ranging between 20 - 50 years. EPO level was measured using enzyme-linked immunosorbent assay (ELISA), the renal parameters (electrolytes) were measured using Ion-Selective Electrodes. Hemoglobin, urea and creatinine were measured using cyanmethemoglobin and colorimetric methods respectively under standard protocols. Demographic and clinical data, including age, gender, diabetes duration, iron rich diet consumption, medication history and family history were collected via questionnaires. Independent sample t-test indicated significantly higher mean hemoglobin (p < 0.05), packed cell volume (p = 0.05) and fasting blood glucose (p < 0.001) in newly diagnosed diabetic patients compared with their healthy control. No significant differences were observed in EPO, creatinine, urea, potassium, bicarbonate, sodium, and chloride between the two groups. In this study, the values of haemoglobin, packed cell volume, EPO and all renal biomarkers were normal, this may be due to the early diagnosis of the disease. It also suggests the extensive capacity of the kidney which is able to withstand metabolic disturbances in the newly diagnosed diabetes mellitus condition. Routine medical check and lifestyle modification are recommended to a newly diagnosed diabetic patients. Also further research is warranted to explore the clinical implications of these assessments in predicting diabetes complications, disease progression and guiding therapeutic interventions.

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]).