Metabolic dynamics in chronic gastritis:Examining urinary profiles post Helicobacter pylori eradication

Chronic gastritis is the persistent and insidious inflammation of the gastric lining.Helicobacter pylori(H.pylori)has been identified as the most common cause of chronic gastritis and consequently elimination of H.pylori can lead to its cure.This editorial explores the use of urinary metabolic profiles before and after eradication to identify biomarkers that can aid in prognosis and treatment.Despite providing promising insights,there are limitations such as a small sample size(17 patients),a narrow treatment period of 2 wk,and treatment heterogeneity,which raise concerns.Nevertheless,these findings have opened a gateway to enhancing the treatment and prognosis of chronic gastritis through urinary metabolomics.

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.

Prevalence and Antibiotic Resistance of Urinary Tract Pathogens, with Molecular Identification of Klebsiella pneumoniae, Klebsiella oxytoca, and Acinetobacter spp., Using Multiplex Real-Time PCR

Urinary tract infections (UTIs) caused by uropathogens are a significant public health problem, and their treatment primarily relies on antibiotic therapy. However, the increasing global development of antibiotic resistance necessitates updating diagnostic techniques to ensure higher sensitivity and specificity, especially with advancements in science and medicine. This study aimed to evaluate the prevalence of UTIs and antibiotic resistance profiles through urine culture, as well as to identify Klebsiella pneumoniae, Klebsiella oxytoca, and Acinetobacter spp. in urine samples using a molecular approach with multiplex real-time PCR. From May 3 to July 25, 2023, at the Pietro Annigoni Biomolecular Research Center (CERBA) and Saint Camille Hospital of Ouagadougou (HOSCO), 209 urine samples collected from patients with suspected UTIs were analyzed using both urine culture and multiplex real-time PCR. Among the 209 patients, 52.15% were male and 47.85% female, with an average age of 46.87 ± 21.33 years. Urine cultures revealed an overall UTI prevalence of 23.44%, with a prevalence of 8.13% in men versus 15.31% in women (P = 0.023). The bacterial prevalence rates were as follows: Escherichia coli (12.92%), Klebsiella spp. (7.18%), Enterobacter cloacae (1.44%), Staphylococcus aureus (0.96%), and other bacteria. Klebsiella spp. demonstrated 100% resistance to Amoxicillin and Amoxicillin/Clavulanic Acid, while Escherichia coli showed 96.2% and 65.4% resistance to Amoxicillin and Amoxicillin/Clavulanic Acid, respectively. PCR analysis of the target bacteria revealed mono-infection prevalence rates of Klebsiella pneumoniae (10.39%), Klebsiella oxytoca (7.79%), and Acinetobacter spp. (7.79%), along with a co-infection prevalence rate of Klebsiella pneumoniae/Acinetobacter spp. (1.30%). This study demonstrated that PCR, with its high sensitivity and specificity, could effectively distinguish Klebsiella pneumoniae from Klebsiella oxytoca and detect Acinetobacter spp. in less than 24 hours—something urine culture alone could not achieve. The relative ease of automating urine PCR testing, combined with its diagnostic accuracy and rapid turnaround time, makes it a valuable addition to modern medical practice for the laboratory diagnosis of UTIs.

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.

慢性肌筋膜触发点模型大鼠的尿液代谢组学分析

背景:慢性肌筋膜触发点通过非靶向代谢组学技术可识别差异性代谢物变化,有助于从内源性小分子代谢物层面理解并进一步探究慢性肌筋膜触发点的病理生理过程和发病机制。目的:以慢性肌筋膜触发点模型大鼠为研究对象,基于尿液代谢组学寻找潜在生物标志物及相关代谢通路。方法:将16只SD大鼠随机分为造模组和正常组,造模组大鼠采用钝性打击结合离心运动(跑台坡度为-16°,跑速为16 m/min,训练时间为90 min/次)方式建立慢性肌筋膜触发点动物模型,每周1次,连续干预8周,休息4周;正常组大鼠不做干预。12周造模结束后,采用代谢笼法收集大鼠造模后24 h尿液,利用液相色谱-质谱联用非靶向代谢组学技术对尿样进行代谢图谱检测,筛选出共同差异代谢物,并进行生物信息学分析。结果与结论:①与正常组相比,造模组有32个差异代谢标志物,其中上调21个、下调11个;依据变量权重值>3,共14个差异代谢物被认定为潜在生物标志物;②京都基因与基因组百科全书富集分析表明,慢性肌筋膜触发点的形成与初级胆汁酸生物合成、花生四烯酸代谢通路密切相关。

液液萃取-超高效液相色谱-串联质谱法同时测定尿液中乌头碱和新乌头碱

建立液液萃取-超高效液相色谱-串联质谱法同时测定尿液中乌头碱和新乌头碱的含量。向尿液样品中加入一定量的萃取溶剂,涡旋,离心,取上层有机相,重复萃取两次,合并萃取液,氮吹至干,再复溶于乙腈中。以乙腈和含0.1%甲酸的2 mmol/L甲酸铵溶液作为流动相,梯度洗脱,采用Acquity BEH C_(18)色谱柱分离,电喷雾离子源正离子方式扫描,多反应监测模式监测,以保留时间和特征离子定性,外标法定量。乌头碱和新乌头碱的质量浓度在1.0~100.0μg/L范围内与其色谱峰面积呈良好的线性关系,相关系数均不小于0.998,方法检出限为0.01μg/L。样品加标平均回收率为99.2%~105.4%,测定结果的相对标准偏差为1.7%~4.1%(n=5)。该方法灵敏度高,准确可靠,适用于食物中毒患者尿液中乌头碱和新乌头碱的检测。

Effects of Different Diuretics on Water Drinking Amount, Urination Volume and Related Blood Indices of Sheep Fed with Cottonseed

[Objective] This study aimed to investigate the effects of three kinds of diuretics on the water drinking amount and urination volume of sheep fed with cottonseed hulls. [Method] The method of self-control was adopted. Five two-year-old male Kazak sheep about 40 kg which never had intake of the feeds containing gossypol were selected. The experiment was divided into five periods, namely the control period, a period with the supplement of 300 mg/d of hydrochlorothiazide, a period with the supplement of 200 mg/d of hydrochlorothiazide, a period with the supplement of 350 mg of GY-01 and a period with the supplement of 200 mg of GY-01. The sheep were fed with the concentrate and the cottonseed hulls in the control period, and corresponding diuretics were supplemented in the rest four periods. The water drinking amount, urination volume and the contents of the hormone and ion in the blood were determined in each period. [Result] After 350 mg GY-01 was supplemented, the water drinking amount of each sheep had an increase of 60.14% compared with that of the sheep in the control period and the urination volume was 2.67 times of that of the latter, and the differences were both significant （P0.01）. The antidiuretic hormone declined by 32.59% compared with that of the sheep in the control period, with the significant difference （P 0.05）. The adrenocorticotropic hormone content increased by 81.93% compared with that of the sheep in the control period and the difference was significant （P0.01）. An increase of 28.04% （P 0.05） and 39.39% （P 0.01） was found in the contents of serum potassium and phosphorus respectively compared with that of sheep in the control period. [Conclusion] The diet with supplement of GY-01 can increase the urination volume of livestock fed with the cottonseed hulls, and the most appropriate supplement amount is 200 mg GY-01.

The Value of the Measurement of Urinary Hyaluronic Acid Levels for the Diagnosis of Bladder Cancer

Objective To investigate the value of the measurement of urinary hyaluronic acid (HA) levels for the diagnosis of bladder cancer and the possibility of replacing ELISA-like assay with radioimmunoassay to detect the levels of urinary HA. Methods Using the ELISA-like assay and radioimmunoassay at the same time to measure the HA levels in the urine specimens from 49 bladder cancer patients, 12 benign bladder tumor patients, 30 other genitourinary disease patients and 20 normal controls. Results There is not much difference between the consequences of the urinary HA levels whether we used the ELISA-like assay or radioimmunoassay to detect every specimen (P>0.05). When we used the results with radioimmunoassay for analysis, we found the levels of urinary HA of bladder cancer patients were 2–4 times than those of the benign bladder tumor patients, other genitourinary disease patients or normal individuals (P<0.01); With 137.5 ngHA/mg protein (113.6±23.9 ng/mg) as a minimum cutoff limit, this assay had a good sensitivity (91.8%) and specificity (91.9%) for the diagnosis of bladder cancer. Its difference in sensitivity meant a lot when compared with urine cytology (48.9%,P<0.01). Conclusion The urinary HA assay is a simple, convenient, noninvasive credible and cheap method with satisfactory sensitivity and specificity for the diagnosis of bladder carcinoma; radioimmunoassay is also a good means to measure the urinary HA levels. Key words Bladder carcinoma - Hyaluronic acid - Urine

改良结扎法用于脊髓损伤造模的优势分析

背景:目前根据脊髓损伤的损伤方式不同衍生出不同的模型构建方法,传统物理损伤造模方法都有各自的优缺点,尚缺乏较为有效和稳定的脊髓损伤动物模型。目的:建立一种可复制、可调控、创伤小、死亡率低、模型更稳定、适用范围广、术后护理时间短的脊髓损伤大鼠模型。方法:将体质量和鼠龄相似的40只SD大鼠随机分为对照组和改良组,每组20只,对照组采用钳夹造模法构建脊髓损伤模型,改良组选用基于压迫法改良的结扎法,在开窗的基础上使用缝线结扎的方法进行脊髓损伤的造模。比较两组大鼠的排尿行为、血尿、脓尿(感染率)、死亡率、脊柱畸形率及术后1,3,5,7 d的BBB运动功能学评分。结果与结论:基于压迫法改良的结扎法建立的脊髓损伤大鼠模型比常规建模方法排尿行为恢复较快、血尿率低、感染率低、死亡率低、脊柱畸形率低,BBB评分结果更集中稳定(1周内均<2分),由此可证明基于压迫法改良的结扎法更适用于脊髓损伤大鼠模型的建立。

影响Urine-H-11干化学法检测尿液分析的因素

Urine—H—11尿液试纸是干化学法检测尿液分析的一种方法，利用干化学法进行尿液分析，能够简便，快速为临床诊断、治疗、预防和监测疾病提供可靠的实验依据，但是，Urine—H—11干化学法也受许多因素的影响，而导致结果的准确性，为了使大家更多的了解影响Urine-H—11干化学法检测尿液的各项因素，准确的为临床提供诊断依据，现将有关Urine—H—11干化学法检测尿液的影响因素总结如下：

Detection of Neisseria Gonorrhoeae from Urine with Ligase Chain Reaction

Objective: To evaluate the value of ligase chainreaction(LCR) in the diagnosis of diplococcusgonorrhoeae in urine. Methods: LCR detection of the urine for Neisseriagonorrhoeae and bacteria culture of discharge was per-formed simultaneously to 276 patients with urethritisor cervicitis seeking treatment in sex transmitted dis-eases (STDs) outpatient clinic. For specimens withdiscordant results, polymerase chain reaction wasconducted. The purpose was to detect the respectivesensitivity and specificity of bacteria culture and LCR. Results: 24 of 276(8.7%) patients had positive LCRresults and 21 of 276(7.6%) were positive for culture.5 specimens had discordant results from LCR andbacteria culture. The sensitivity and specificity of LCRin the diagnosis of gonorrhoeae were 92.3% and100% respectively. Conclusion: This study showed that LCR had ahigher sensitivity and specificity for the diagnosis ofgonorrhoeae from urine.

聚乙二醇洛塞那肽注射液与恩格列净治疗2型糖尿病早期糖尿病肾病的疗效比较

目的比较聚乙二醇洛塞那肽注射液(PEX168)与恩格列净治疗2型糖尿病(T2DM)早期糖尿病肾病(DKD)的临床疗效。方法选取2020年2月—2021年2月入住郴州市第一人民医院内分泌科的T2DM早期(G2A2期)DKD患者60例,采用随机数字表法分为PEX168组(n=30)和恩格列净组(n=30),分别给予聚乙二醇洛塞那肽注射液与恩格列净治疗,2组均治疗24周。比较2组治疗前、治疗12周、24周后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA_(1c))、胰岛素抵抗指数(HOMA-IR)]、血压[收缩压(SBP)、舒张压(DBP)]、肾功能指标[尿白蛋白—肌酐比值(UACR)、估算肾小球滤过率(eGFR)]、体质指数(BMI)、内脏脂肪面积,不良反应。结果治疗12周、24周后,2组血糖指标(FPG、2 hPG、HbA_(1c)、HOMA-IR)、血压(SBP、DBP)均低于治疗前,且PEX168组治疗12周、24周后的SBP和治疗24周后的HOMA-IR、DBP均低于恩格列净组(P<0.05或P<0.01),组间其他指标比较差异均无统计学意义(P>0.05)。治疗12周、24周后,2组eGFR高于治疗前,UACR、BMI及内脏脂肪面积低于治疗前,且PEX168组治疗24周后eGFR高于恩格列净组,UACR、BMI及内脏脂肪面积低于恩格列净组(P<0.05或P<0.01),2组治疗12周后eGFR、UACR、BMI及内脏脂肪面积比较差异均无统计学意义(P>0.05)。2组均无严重不良反应发生。结论聚乙二醇洛塞那肽注射液与恩格列净均有明显的降糖及肾脏保护作用,但聚乙二醇洛塞那肽注射液对超重及腹型肥胖的T2DM早期DKD患者的肾脏保护作用更好。

完全性脊髓横断后排尿次数对神经源性膀胱模型大鼠成模率的影响

背景:脊髓损伤常导致逼尿肌反射亢进型神经源性膀胱,目前对其发病机制和治疗缺乏明确认识,建立稳定可靠的动物模型对揭示疾病的病理机制和探索治疗方法具有重要影响。目的:探究完全性脊髓横断术后辅助排尿次数对神经源性膀胱模型大鼠的影响,以提高神经源性膀胱模型大鼠术后生存率及成模率。方法:从46只雌性SD大鼠中按随机数字表法抽取6只为假手术组,剩余40只大鼠完全性脊髓横断造模后随机分为每日排尿0,1,3,5次组,每组10只。术后19 d内每隔3 d测量残余尿量,术后第19天时观察存活及成模情况,进行尿流动力学检测及离体逼尿肌肌条收缩实验。结果与结论:①存活率及成模率:每日排尿0次组存活率10%,成模率10%;每日排尿1次组存活率20%,成模率10%;每日排尿3,5次组存活率70%,成模率70%;②残余尿量:与假手术组相比,术后第3,6,9,12,15天,每日排尿3,5次组的残余尿量显著增加(P<0.01);术后第18天,每日排尿3,5次组的残余尿量增多(P<0.05);与每日排尿3次组相比,术后第6天,每日排尿5次组的残余尿量减少(P<0.05),术后第3,9,12,15,18天,每日排尿5次组的残余尿量无统计学差异;③尿流动力学:与假手术组相比,每日排尿3,5次组大鼠的漏尿点压差明显减小(P<0.01),膀胱最大容量显著增大(P<0.01);与每日排尿3次组相比,每日排尿5次组的漏尿点压差和膀胱最大容量均无统计学差异;④离体逼尿肌肌条收缩实验:与假手术组相比,每日排尿3,5次组逼尿肌肌条收缩幅度和频率显著减少(P<0.01);与每日排尿3次组相比,每日排尿5次组的逼尿肌肌条收缩幅度和频率均无统计学差异。结果表明:辅助排尿是成功构建逼尿肌反射亢进型神经源性膀胱模型的影响因素之一,每日排尿3次或5次无明显差异,结合实际工作量和成模率,建议每日排尿频率至少3次及以上。

辅料童便在我国中药炮制中的历史应用、炮制作用以及现代研究进展

童便作为炮制辅料,在我国中药炮制中的应用已久,我国古代炮制三专著《雷公炮炙论》《炮制大法》《修事指南》以及众多医药典籍均有明确记载,童便的应用几乎贯穿了中医药大部分发展时期。本文系统总结了辅料童便在我国中药炮制中的历史应用、炮制作用以及现代研究进展,分析目前面临的困境,并提出相应的对策与未来的研究方向,以期为科学传承和发展童便炮制法提供文献参考。

平面流式图像技术全自动尿液分析系统复检规则的建立与验证

目的对迪瑞FUS-3000Plus全自动尿液分析系统尿干化学与尿有形成分联合检测制定复检规则并进行验证。方法收集2019年1—6月北京市垂杨柳医院门诊及住院尿液标本共1300例,其中1000例用于建立复检规则,300例用于验证和调整复检规则。所有标本采用FUS-3000Plus进行干化学与尿有形成分检测和采用Fast Read-10尿沉渣定量分析板进行显微镜镜检。将尿有形检测项目白细胞(WBC)、红细胞(RBC)、管型(CAST)和与之分别对应的干化学检测项目白细胞酯酶(LEU)、尿潜血(BLD)、尿蛋白(PRO)的阴性、阳性两种结果作为复检规则的筛选表达式,以显微镜镜检结果为金标准,筛选适合本实验室的复检规则,并采用假阴性率、复检率等国内外通用的复检规则评估指标评价规则的合理性和可行性。结果以镜检结果为标准,统计1000份尿标本检测结果,初步制定出42条复检规则,计算应用规则后其假阴性率和复检率分别为2.60%和27.80%;统计300份验证标本检测结果,将复检规则精简为38条,并计算得到验证样本真阳性率为22.33%,假阳性率19.67%,真阴性率57.33%,假阴性率为0.67%,复检率为17%。结论本院建立42条尿复检规则经300份临床样本测试验证精简为38条尿复检规则满足临床测试要求,可将复检规则应用于临床。

Regional Differences of the Urinary Proteomes in Healthy Chinese Individuals

Objective Urine is a promising biomarker source for clinical proteomics studies.Regional physiological differences are common in multi-center clinical studies.In this study,we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China.Methods In this study,morning urine samples were collected from healthy urban residents in three regions of China(Haikou,Xi’an and Xining)and urinary proteins were preserved using a membrane-based method(Urimem).The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions.Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database,and pathway enrichment of the differential urinary proteins was analyzed using KEGG.Results We identified 1898 proteins from Urimem samples using label-free proteome quantification,of which 56 urine proteins were differentially expressed among the three regions(P<0.05).Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than intersex differences.After gender stratification,16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples.Among these differential proteins,several proteins have been previously reported as urinary disease biomarkers.Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection.Regional differences are a confounding factor influencing the urine proteome and should be considered in future multicenter biomarker studies.

人尿源性干细胞的分离培养及诱导分化为平滑肌细胞

背景:传统尿路修复重建手段受限于供体短缺、并发症多以及生理功能恢复不理想等问题,组织工程策略为此领域提供了新方向。鉴于尿路主要由肌性组织构成,其中关键在于发掘适合的种子细胞并高效诱导分化为平滑肌细胞,但关于不同平滑肌细胞诱导方案效能的对比研究仍较为匮乏。目的:旨在分离、培养及鉴定人尿源性干细胞,并比较两种不同成平滑肌诱导方案的效果。方法:采用多次离心法从11份健康成人志愿者尿液中分离提取尿源性干细胞,使用流式细胞仪进行表面标志物的鉴定,通过成骨、成脂诱导分化来验证尿源性干细胞的多向分化潜能。尿源性干细胞分别在含转化生长因子β1以及转化生长因子β1联合血小板衍生生长因子的成平滑肌细胞诱导分化培养基中诱导分化14 d,采用免疫荧光染色和Western blot检测平滑肌特异性蛋白(α-SMA、SM22)的表达差异。结果与结论:①成功从8份健康人尿液中分离出尿源性干细胞,细胞呈“米粒”样,具有很好的分裂增殖能力;②尿源性干细胞高表达间充质干细胞表面标志物CD73、CD90和CD44,极低表达造血干细胞表面标志物CD34和CD45,不表达CD19、CD105和HLA-DR;③经成骨和成脂诱导分化后,可见明显的钙结节和脂滴形成,茜素红染色和油红O染色结果呈阳性;④成平滑肌诱导培养14 d,免疫荧光染色显示转化生长因子β1/血小板衍生生长因子组尿源性干细胞成平滑肌诱导分化率显著高于转化生长因子β1组(P<0.005);⑤成平滑肌诱导培养14 d,Western blot检测显示转化生长因子β1/血小板衍生生长因子组α-SMA和SM22蛋白表达量显著高于转化生长因子β1组(P<0.005)。结果表明:尿源性干细胞可以通过多次离心法无创分离获取;相较于单纯转化生长因子β1,转化生长因子β1/血小板衍生生长因子联合应用能显著提高尿源性干细胞诱导分化为平滑肌细胞的效率。

Renal effects and safety of tirzepatide in subjects with and without diabetes:A systematic review and meta-analysis

BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.