To evaluate the value of ureteral wall thickness (UWT) obtained from non-contrast computed tomography (NCCT) for predicting difficult ureter (DU) among patients receiving ureteroscopic lithotripsy (URS). Patients with unilateral ureteral stones managed by URS were retrospectively reviewed. According to intraoperative findings, they were classified into DU or non-DU group. UWT was measured at the level of the stone on preoperative NCCT. Multivariate logistic regression was used to identify independent predictors. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of UWT for predicting DU. A total of 271 patients managed with URS were enrolled in the study, with 67 (24.72
Background: Prostate-specific membrane antigen (PSMA) PET/CT can detect clinically significant prostate cancer (csPCa), but no validated multi-parameter reporting framework analogous to PI-RADS for mpMRI exists. We aimed to develop and externally validate a multi-parameter, rule-based integer PSMA PET/CT scoring system across multiple tracers. Methods: In this multicentre, diagnostic accuracy study, we derived C-SUDA-5 (China-Soochow University-5) using a development cohort (n=747; six centres; four PSMA tracers) through LASSO regression, converting five retained PSMA PET-derived parameters into an integer score (range −1 to 11; five risk groups). We externally validated in a temporal cohort (n=100, from the originating centre) and a spatial cohort (n=190, from an independent centre), comparing discrimination against PI-RADS, PRIMARY score, miPSMA, and a 5-point Likert scale. Findings: C-SUDA-5 yielded area under the curve (AUC) of 0·880 (development, four tracers) and 0·864–0·869 (two independent external cohorts), outperforming PI-RADS, PRIMARY, and miPSMA (all P<0·05). csPCa rates increased stepwise from 7–14% (G1) to 99–100% (G5). The recommended C-SUDA-5 strategy (G1 follow-up, G2–5 biopsy) achieved miss rates of 1·6–3·0% with correct avoidance rates of 19·0–20·0%. Interpretation: C-SUDA-5 discriminated csPCa with accuracy comparable to experienced nuclear medicine physicians (Likert mean AUC 0·875) with higher inter-rater reliability (grade kappa 0·990 vs 0·226). This rule-based integer scoring system may provide a standardised and reproducible approach to PSMA PET/CT reporting before biopsy. Prospective interventional trials are needed to evaluate clinical impact.
BackgroundComputed tomography (CT) Hounsfield units (HUs) of pathologically confirmed metastatic inguinal lymph nodes (ILNs) were proved to be higher than negative ones. We designed this study to explore the clinical value of CT HU for diagnosing palpable ILN metastasis in patients with penile cancer.MethodsA total of 32 patients with penile cancer, including 84 palpable ILNs, were recruited in this study. They all performed 5-mm layer pelvic contrast-enhanced CT (CE-CT) before treatment. The palpable ILNs were matched with CT image. By using radiologic software PACS, the layer with a maximum cross-sectional area of target lymph node was selected, and the short axis was defined as diameter. We outlined the edge of target lymph nodes, and the software automatically calculated its area, maximum CT HU, and average CT HU. All target ILNs were biopsied by surgery to confirm the presence of metastasis.ResultsCompared with non-metastatic ILNs, metastatic ILNs had larger diameter, area, maximum non-contrast CT (NC-CT) HU, maximum arterial-phase CE-CT (ACE-CT) HU, average NC-CT HU, and average ACE-CT HU, with statistically significant differences (P < 0.05). Receiver operating characteristic analysis showed the all six parameters (maximum NC-CT HU, maximum ACE-CT HU, average NC-CT HU, average ACE-CT HU, diameter, and area) had significant diagnostic value for ILN metastasis, with an area under the curve of 0.847, 0.853, 0.900, 0.919, 0.809, and 0.789, respectively. The average ACE-CT HU (cutoff: 40.5) had the highest accuracy as 0.857, and maximum NC-CT HU (cutoff: 51.5) had the highest sensitivity of 0.897.ConclusionILN CT HU was clinically valuable for the diagnosis of palpable ILN metastasis in patients with newly diagnosed penile cancer.
Introduction:Accurate prediction of bone metastasis at diagnosis is crucial for optimizing management in prostate cancer (PCa) patients. While clinical parameters like PSA and Gleason score are established predictors, their accuracy is suboptimal. Systemic inflammation, reflected in biomarkers like the high-sensitivity C-reactive protein-to-albumin ratio (HAR), fibrinogen (FIB), and hemoglobin (HB), has emerged as a key player in cancer progression, yet its integration into clinical predictive tools remains underexplored. Methods:In this retrospective study of 803 newly diagnosed PCa patients, we developed and validated two nomograms for predicting bone metastasis. A baseline clinical model was constructed using total prostate-specific antigen (TPSA) and biopsy Gleason grade groups. An enhanced comprehensive model integrated these clinical parameters with inflammatory markers (HAR, FIB, HB). Model performance was rigorously assessed through discrimination (ROC analysis, AUC), calibration (calibration curves, Hosmer-Lemeshow test), and clinical utility (Decision Curve Analysis). Internal validation was performed via bootstrapping. Results:Multivariate analysis confirmed TPSA, FIB, HB, HAR, and Gleason grade groups as independent predictors of bone metastasis. The comprehensive model demonstrated significantly superior discriminative ability, achieving an AUC of 0.874 (95% CI: 0.845-0.902) compared to 0.830 (95% CI: 0.798-0.863) for the clinical model (Delong's test, P < 0.01). This translated to a net improvement in reclassification (NRI: 8.96%) and overall predictive performance (IDI: 10.3%). The model was well-calibrated and provided a positive net benefit across a wide range of clinical threshold probabilities. Conclusion:We present a novel, internally validated nomogram that synergistically combines inflammatory and clinical markers to accurately predict bone metastasis in PCa at initial diagnosis. This practical and cost-effective tool has the potential to aid clinicians in risk stratification, guide personalized diagnostic imaging decisions, and ultimately help reduce unnecessary bone scans, particularly in resource-conscious settings. Our findings underscore the pivotal role of the systemic inflammatory response in PCa metastasis.
ObjectiveThe purpose of this study was to investigate the clinical significance of serum high sensitive C-reactive protein/albumin ratio in primary prostate biopsy.MethodsRetrospective analysis was done on the clinical data of 1679 patients who had their first transrectal or perineal prostate biopsy at our situation from 2010 to 2018. Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) were the pathologic diagnoses in 819 and 860 cases, respectively. A comparison was made between the HAR differences between PCa and BPH patients as well as the positive prostate biopsy rate differences between groups with increased and normal HAR. The results of the prostate biopsy were examined using logistic regression, and a model for predicting prostate cancer was created. The receiver characteristic curve (ROC) was used to determine the model’s prediction effectiveness. The clinical models integrated into HAR were evaluated for their potential to increase classification efficacy using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). According to the Gleason score (GS) categorization system, prostate cancer patients were separated into low, middle, and high GS groups. The differences in HAR between the various groups were then compared. The prevalence of high GSPCa and metastatic PCa in normal populations and the prevalence of higher HAR in prostate cancer patients were compared using the chi-square test.ResultPatients with PCa had a median HAR (upper quartile to lower quartile) of 0.0379 (10-3), patients with BPH had a median HAR (0.0137 (10-3)), and the difference was statistically significant (p<0.05). Patients with increased HAR and the normal group, respectively, had positive prostate biopsy rates of 52% (435/839)and 46% (384/840), and the difference was statistically significant (p<0.05). Logistic regression analysis showed that HAR (OR=3.391, 95%CI 2.082 ~ 4.977, P < 0.05), PSA density (PSAD) (OR=7.248, 95%CI 5.005 ~ 10.495, P < 0.05) and age (OR=1.076, 95%CI 1.056 ~ 1.096, P < 0.05) was an independent predictor of prostate biopsy results. Two prediction models are built: a clinical model based on age and PSAD, and a prediction model that adds HAR to the clinical model. The two models’ ROC had area under the curves (AUC) of 0.814 (95%CI 0.78-0.83) and 0.815 (95%CI 0.79-0.84), respectively. When compared to a single blood total PSA (tPSA) with an AUC of 0.746 (95%CI 0.718-0.774), they were all superior. Nevertheless, there was no statistically significant difference (p<0.05) between the two models. We assessed the prediction model integrated into HAR’s capacity to increase classification efficiency using NRI and IDI, and we discovered that NRI>0, IDI>0, and the difference was statistically significant (P>0.05).There was a statistically significant difference in HAR between various GS groups for individuals who had prostate cancer as a consequence of biopsy (p<0.05). The incidence of high GS and metastatic patients was statistically significantly greater (p<0.05) in the HAR elevated group (90.1%and 39.3%, respectively) than in the HAR normal group (84.4% and 12.0%).ConclusionProstate biopsy results that were positive were impacted by HAR, an independent factor that increased with the rate of PCa discovery. Patients with elevated HAR had a greater risk of high GS as well as metastatic PCa among those with recently diagnosed prostate cancer through prostate biopsy.
This study aimed to investigate the optimal screening interval of a prostate specific antigen (PSA) screening program for men aged 40-70 with a baseline PSA < 2 ng/mL in China. 8-year period clinical data of Chinese males who underwent physical examination annually in our hospital were retrospectively collected. 397 healthy males were included.Total PSA (tPSA) and free PSA (fPSA) were collected, and the free/total PSA ratio (f/t PSA) was calculated. According to the baseline PSA value, study population was divided into 2 groups: 0-0.99 ng/mL and 1-1.99 ng/mL. Prostate biopsy indicates at tPSA > 10 ng/mL, or 4-10 ng/mL (gray area) and f/t PSA < 0.16. Kaplan-Meier survival analysis was used to calculate the relevant cumulative incidence rate. Over the eight-year screening period, 27 people (6.8%) had abnormal PSA that met prostate biopsy criteria. 7 cases of prostate cancer were detected (detection rate 25.9%) among the 27 patients who performed a biopsy. In the 0-0.99 ng/mL and 1-1.99 ng/mL group, 4.1% (13/317) and 17.5% (14/80) achieved biopsy criteria within 8 years, with a statistically significant difference (p p < 0.001). In both groups, abnormal PSA began appearing in the sixth year. According to stratifying the cohort age and PSA, abnormal PSA levels began to appear in all subgroups by the sixth year, except for men aged < 50 years plus baseline PSA < 1 ng/mL, where they appeared by the seventh year. Furthermore, in the group of baseline 40-49 years and baseline PSA < 2 ng/mL, the probability of meeting biopsy indications during eight years was very low (1.4%, 2/143). Chinese men aged 50-70 with baseline PSA < 2 ng/mL should undergo for PSA retest in the sixth year, while aged 40-49 with a baseline PSA < 2 ng/mL do not need PSA screening within eight years.
Background Radical cystectomy and urinary diversion are the standard surgical treatments for patients with muscle-invasive or high-risk, or recurrent non-muscle-invasive bladder cancer. Although this approach significantly prolongs patient survival, it can lead to postoperative complications. This study aims to compare the efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma to those of cutaneous ureterostomy with two stomas and an ileal conduit as a means of urinary diversion after radical cystectomy. The findings of this study will provide valuable information for healthcare providers in selecting the appropriate urinary diversion method for their patients. Methods The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomy were retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs,and postoperative quality of life were compared between the three groups of patients. Results A significant difference in the operative time was found between the three groups ( P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or bladder cancer index (BCI) score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant ( P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients ( P = 0.006). Conclusion A single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy may result in shorter surgery time, increased success rates for initial catheter removal, and lower medical expenses. However, to confirm these findings, further prospective randomized clinical trials are necessary.
Renal cell carcinoma, shorted as RCC is a well-known urological cancer with high level of morbidity and mortality. Although the regulatory role of the spindle microtubule assembly factor (ASPM) in tumor progression has been established, its relationship to the development of RCC remains unclear. To determine the significance of this gene in RCC, we examined its expression in RCC patients in the TCGA database and compared ASPM level between clinical samples of normal tissues and RCC tissues collected at our center. The prognostic relevance of ASPM was assessed by generating Kaplan-Meier survival curves and log-rank functions. Following alteration of ASPM expression using sh-ASPM or oe-ASPM transfection, RCC cell characteristics were evaluated through CCK-8, Transwell, and colony formation assays. Western blot analysis was conducted to measure levels of genes affected by ASPM, and rescue experiments were performed to explore the involvement of Wnt3a signaling in ASPM-mediated malignancy in RCC. Our findings indicate that ASPM is upregulated in RCC samples, and its levels are associated with the long-term survival of RCC patients. ASPM promotes the migration, proliferation, and invasiveness of RCC cells, and the Wnt3a pathway may be implicated in this process. In conclusion, these results indicate that ASPM contributes to the cancer progression of RCC by targeting the Wnt3a signaling pathway.
Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.
Background The global morbidity and mortality of prostate cancer (PCa) increase sharply every year. Early diagnosis is essential; it determines survival and outcome. So, this study extracted the texture features of apparent diffusion coefficient images in multiparametric magnetic resonance imaging (mp-MRI) and built machine learning models based on radiomics texture analysis (TA) to determine its ability to distinguish benign from PCa lesions using the Prostate Imaging Reporting and Data System (PI-RADS) 4/5 score. Methods We enrolled 103 patients who underwent mp-MRI examinations and transrectal ultrasound and magnetic resonance fusion imaging (TRUS-MRI) targeted prostate biopsy and obtained pathological confirmation at our hospital from August 2017 to January 2020. We used ImageJ software to obtain texture feature parameters based on apparent diffusion coefficient (ADC) images, then standardized texture feature parameters, and used LASSO regression to reduce multiple feature parameters; 70% of the cases were randomly selected from the PCa group and the benign prostate hyperplasia group as the training set. The remaining 30% was used as the test set. The machine learning classification model for identifying benign and malignant prostate lesions was constructed using the feature parameters after dimensionality reduction. The clinical indicators were statistically analyzed, and we constructed a machine learning classification model based on clinical indicators of benign and malignant prostate lesions. Finally, we compared the model’s performance based on radiomics texture features and clinical indicators to identify benign and malignant prostate lesions in PI-RADS 4/5 score. Results The area under the curve (AUC) of the R-logistic model test set was 0.838, higher than the R-SVM and R-AdaBoost classification models. At this time, the corresponding R-logistic classification model formula is as follow: Y_radiomics=9.396-7.464*median ADC-0.584*kurtosis+0.627*skewness+0.576*MRI lesions volume; analysis of clinical indicators shows that the corresponding C-logistic classification model formula is as follows: Y_clinical =-2.608+0.324*PSA-3.045*Fib+4.147*LDL-C, the AUC value of the model training set was 0.860, smaller than the training set R-logistic classification model AUC value of 0.936. Conclusions Radiomics combined with the machine learning classifier model has strong classification performance in identifying benign and PCa in PI-RADS 4/5 score. Various treatments and outcomes for PCa patients can be applied clinically.
目的:探讨全前列腺表观弥散系数图纹理特征与前列腺癌根治术后病理Gleason评分(gleason score,GS)升高(gleason upgrading,GU)是否有相关性.方法:回顾性分析苏州大学附属第一医院2016年1月—2019年11月术前穿刺病理GS 6分的56例腹腔镜前列腺癌根治患者,计算出全前列腺和全前列腺基于阈值的ADC平均值、中位数、25和75百分位数、峰度、偏度和熵等ADC纹理参数.比较术后病理GS升高(GU)组和GS未升高(gleason non-upgrading,GN)组ADC纹理参数的差异;评价各参数和GU的相关性,ROC曲线评价各参数的诊断效能.结果:56例术前GS 6分患者根治术后GS 6分28例(50.00%),GU组的全前列腺ADC熵为(9.87±0.29),显著高于G N组的(9.65±0.43)(t=2.197,P=0.032<0.05);G U组的基于阈值的A D C平均值为(0.801±0.047)×10-3?m m2/s,显著低于GN组的(0.842±0.042)×10-3?mm2/s(t=3.413,P=0.001<0.05),全前列腺ADC熵和基于阈值的ADC平均值预测GU的AUC值分别为0.657和0.786.Logistic多因素回归分析显示全前列腺ADC熵高和基于阈值的ADC平均值低是GU的独立危险因素.结论:全前列腺ADC熵和基于阈值的ADC平均值与GU有明显相关性.
目的:提取泌尿系结石的全体积CT纹理参数,分析全体积CT纹理参数与结石成分和钬激光碎石手术时间的关系,探讨全体积CT纹理分析在泌尿系结石的临床应用价值.方法:回顾性分析2018年1月-2019年10月在无锡市人民医院住院接受钬激光碎石手术治疗并进行结石成分分析的104例泌尿系结石患者的临床资料.用相关软件处理CT中的结石图像、转换为数值.提取整个结石全体积的每一个像素CT值,计算出全体积CT纹理参数,包括均值、中值、和、25百分位数、75百分位数、极大值、极小值、全距、峰度、偏度和熵(En-tropy).比较尿酸结石、草酸钙结石和混合结石三组患者之间全体积CT纹理参数的差异;分析全体积CT纹理参数和钬激光碎石手术时间的相关性.结果:全体积CT纹理参数中,尿酸结石组的均值、中值、全距、极大值、25百分位数、75百分位数显著低于草酸钙结石组和混合结石组(P<0.05),熵、峰度和偏度在尿酸结石组、草酸钙结石组和混合结石组中无明显差异(P>0.05);全体积CT纹理参数中Entropy,25百分位数、和、中值和偏度在钬激光碎石手术时间两组比较差异有统计学意义(P<0.05).其中Entropy、25百分位数及和与钬激光碎石手术时间成正相关性;偏度呈负相关性.Entropy呈最强的正相关性(r>0.5,Pearson和Spearman相关系数同时满足),25百分位数与和呈现较强的正相关性(0.3<r<0.5,Pearson和Spearman相关系数同时满足),偏度呈现中等强度负相关性(r=-0.351,Pearson相关系数;r=-0.345,Spearman相关系数).结论:全体积CT纹理参数中,均值、中值、全距、极大值、25百分位数和75百分位数在尿酸结石组中明显低于非尿酸结石组,这些纹理参数有望被选用来帮助区分尿酸结石和非尿酸结石;Entropy、25百分位数及和与钬激光碎石手术时间正相关,偏度与钬激光碎石手术时间负相关,这些纹理参数的测量有助于术前评估钬激光碎石手术的难易程度.
目的:评估全病灶表观弥散系数(ADC)图像的熵值对前列腺癌(PCa)的临床诊断价值及效能.方法:选取我院2017年8月—2020年1月接受经直肠超声与磁共振融合成像(TURS-MRI)靶向前列腺穿刺的并取得病理报告的110例患者作为研究对象,分为前列腺癌组和前列腺增生组.首先,所有患者穿刺前行多参数磁共振(mp-MRI)检查,并结合T2图像、扩散加权成像(DWI)和DCE图像以确定病灶大小及层面;其次,根据ADC图像对所有病灶进行勾画并计算其ADC熵值;再次,利用独立样本t检验评价两组患者的熵值差异是否显著;最后,采用受试者操作特征曲线(ROC)计算曲线下面积(AUC)来评定ADC熵值的效能.结果:前列腺增生组患者和前列腺癌组患者的全病灶ADC熵值比较差异有统计学意义(P<0.01);ROC曲线下面积为90.20%,前列腺癌诊断的截点值为6.23.结论:全病灶ADC熵值的诊断效能较高,也即全病灶ADC熵值对前列腺癌的诊断具有一定的价值,可为临床诊治提供帮助.
Background: To extract the texture features of Apparent Diffusion Coefficient (ADC) images in Mp-MRI and build a machine learning model based on radiomics texture analysis to determine its ability to distinguish benign from prostate cancer (PCa) lesions using PI-RADS 4/5 score.Materials and methods: First, use ImageJ software to obtain texture feature parameters based on ADC images; use R language to standardize texture feature parameters, and use Lasso regression to reduce the dimensionality of multiple feature parameters; then, use the feature parameters after dimensionality reduction to construct image-based groups. Learn R-Logistic, R-SVM, R-AdaBoost to identify the machine learning classification model of prostate benign and malignant nodules. Secondly, the clinical indicators of the patients were statistically analyzed, and the three clinical indicators with the largest AUC values were selected to establish a classification model based on clinical indicators of benign and malignant prostate nodules. Finally, compare the performance of the model based on radiomics texture features and clinical indicators to identify benign and malignant prostate nodules in PI-RADS 4/5.Results: The experimental results show that the AUC of the R-Logistic model test set is 0.838, which is higher than the R-SVM and R-AdaBoost classification models. At this time, the corresponding R-Logistic classification model formula is: Y_radiomics=9.396-7.464*median ADC-0.584 *kurtosis+0.627*skewness+0.576*MRI lesions volume; analysis of clinical indicators shows that the 3 indicators with the highest discrimination efficiency are PSA, Fib, LDL-C, and the corresponding C-Logistic classification model formula is: Y_clinical =-2.608 +0.324*PSA-3.045*Fib+4.147*LDL-C, the AUC value of the model training set is 0.860, which is smaller than the training set R-Logistic classification model AUC value of 0.936.Conclusion: The machine learning classifier model is established based on the texture features of radiomics. It has a good classification performance in identifying benign and malignant nodules of the prostate in PI-RADS 4/5. This has certain potential and clinical value for patients with prostate cancer to adopt different treatment methods and prognosis.
BACKGROUND:Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). METHODS:The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. RESULTS:The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. CONCLUSION:The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.
Abstract Background Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients. Methods A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed. Results Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4+/CD8+, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis. Conclusion This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.
目的:评估全病灶ADC定量分析对前列腺成像报告和数据系统版本2(PI-RADS v2)评分4/5分病灶患者的前列腺癌(PCa)诊断价值.方法:选取经直肠超声与磁共振融合(TURS-MRI)靶向前列腺穿刺患者中mp-MRI存在PI-RADS v2评分4/5分病灶的55例为研究对象.根据T2、DWI和ADC图确定病灶位置及层面,提取所有层面病灶每个像素ADC值,计算第25百分位(P25)ADC值、第75百分位(P75)ADC值、平均ADC值和中位ADC值,根据病理结果分为前列腺癌组(PCa组)和良性病灶组(BPH组);采用独立样本t检验比较两组之间有无差异;采用受试者操作特征(ROC)曲线计算曲线下面积(AUC),评定每个指标诊断PCa的效能.结果:PCa组P25 ADC值、P75 ADC值、平均ADC值、中位ADC值均低于BPH组,差异有统计学意义(P<0.05).ROC曲线结果分析显示,平均ADC值的ROC曲线下面积最大为0.813,当约登指数最大时,诊断PCa的平均ADC截点值为0.89×10-3mm2/s,敏感度和特异度分别为60.4%和100%.结论:全病灶ADC定量分析有助于PI-RADS v2评分诊断PCa.全病灶平均ADC值诊断PCa的AUC最大,提示全病灶平均ADC值在PI-RADS v2评分4/5分患者中的辅助诊断作用值得进一步研究.
BACKGROUND Klotho deficiency has been implicated in various kidney diseases and has been associated with renal fibrosis. However, the role of Klotho in renal allograft fibrosis still remains undetermined. MATERIAL AND METHODS A 24-week-old rat renal transplant model with chronic allograft dysfunction (CAD) was carried out by orthotopic kidney transplantation using F344 donor rats to Lewis recipient rats. Successful establishment of the model was verified by HE and Masson staining and renal allograft function assessment. HK-2 cells were cultured and treated with TGF-ß1 and/or siRNA-Klotho at various time points. Total proteins and RNA were extracted from the cultured cells and kidney tissues. Western blot assay and quantitative RT-PCR were used to analyze the expression of Klotho, fibronectin, and ß-catenin pathways. RESULTS We successfully established and identified a 24-week-old rat renal transplant model with CAD. Loss of Klotho was identified to be associated with epithelial-to-mesenchymal transition (EMT), renal allograft fibrosis, and CAD. In HK-2 cells, a significant decrease of Klotho protein was observed in the renal fibrosis induced by TGF-ß1 in a time-dependent manner. Moreover, intervention of siRNA-Klotho remarkably promoted the progression of renal fibrosis and activation of the Wnt/ß-catenin signaling pathway. CONCLUSIONS Our results show that Klotho has a significant protective role against EMT, renal allograft fibrosis, and CAD following kidney transplantation, which is mediated by inhibition of the Wnt/ß-catenin signaling pathway.
To investigate the clinical effect of neoadjuvant chemotherapy on locally advanced prostate cancer, a case of prostate cancer in our hospital in 2019 was retrospectively analyzed. Preoperative PSA was 37.4ng/ml, clinical stage was T 4N 1M 0, and bone scan was negative. In order to reduce the difficulty of operation and postoperative complications, we treated the patients with neoadjuvant endocrine therapy plus 4 courses of neoadjuvant chemotherapy (docetaxel). Laparoscopic radical prostatectomy was successfully performed in the patient, and there was no biochemical recurrence after 1 year follow-up.
Although prostate biopsy is the gold standard for the diagnosis of prostate cancer, it also leads to high incidence of negative biopsies and the diagnosis of clinically low-risk prostate cancer and the subsequent overtreatment. It remains an unmet need to discover new biomarkers in order to defer the unnecessary biopsies in clinical practice. In this study, we described a new method, LBXexo score, to measure the urine exosomal PCA3/PRAC expression from non-DRE urine as a noninvasive diagnosis to improve the detection rate in Chinese population with a low serum PSA level. First-voided urine samples were collected to isolate exosomes, and exosomal RNAs of PCA3 and PRAC were measured by quantitative reverse transcription PCR. A significant increase in exoPCA3/PRAC was observed in both any-grade and high-grade prostate cancer groups when compared with the biopsy-negative group. Receiver-operating characteristic curve analyses showed that the LBXexo score significantly improved diagnostic performance in predicting biopsy results, with AUCs of 0.723 (p=0.017) and 0.736 (p=0.038) for any-grade and high-grade (GS ≥ 7) prostate cancer, respectively. For high-grade cancer, LBXexo had the negative and positive predictive values of 100% and 27.59%, respectively, and could potentially avoid unnecessary biopsy. This is the first report in Chinese population that demonstrates the predictive value of the exosomal expression of PCA3 and PRAC derived from non-DRE urine in predicting prostate biopsy outcomes. It could be used in clinical practice to make a better informed biopsy decision and avoid unnecessary biopsies in Chinese population.