Machine learning application identifies plasma markers for proteinuria in metastatic colorectal cancer patients treated with Bevacizumab.

BACKGROUND AND OBJECTIVES: Proteinuria is a common complication after the application of bevacizumab therapy in patients with metastatic colorectal cancer, and severe proteinuria can lead to discontinuation of the drug. There is a lack of sophisticated means to predict bevacizumab-induced proteinuria, so the present study aims to predict bevacizumab-induced proteinuria using peripheral venous blood samples. METHODS: A total of 122 subjects were enrolled and underwent pre-treatment plasma markers, and we followed them for six months with proteinuria as the endpoint event. We then analyzed the clinical features and plasma markers for grade ≥ 2 proteinuria occurrence using machine learning to construct a model with predictive utility. RESULTS: One hundred sixteen subjects were included in the statistical analysis. We found that high baseline systolic blood pressure, low baseline HGF, high baseline ET1, high baseline MMP2, and high baseline ACE1 were risk factors for the development of grade ≥ 2 proteinuria in patients with metastatic colorectal cancer who received bevacizumab. Then, we constructed a support vector machine model with a sensitivity of 0.889, a specificity of 0.918, a precision of 0.615, and an F1 score of 0.727. CONCLUSION: We constructed a machine learning model for predicting grade ≥ 2 bevacizumab-induced proteinuria, which may provide proteinuria risk assessment for applying bevacizumab in patients with metastatic colorectal cancer.

Perfusion preparation of the rat bladder decellularized scaffold.

Introduction: Bladder reconstruction is a huge challenge in the field of urology. In recent years, perfusion methods have brought promising results in the field of tissue engineering. We prepared bladder decellularized scaffolds by improved perfusion, which may be suitable for bladder reconstruction. Methods: We prepared decellularized scaffolds of rat bladder by perfusion of SDS (0.5% sodium dodecyl sulfate), SDS-SDC (0.5% sodium dodecyl sulfate +0.5% sodium deoxycholate). Histological characteristics of bladder decellularized scaffolds were assessed by Hematoxylin and eosin, Masson, and DAPI staining. Moreover, we also prepared a murine bladder transplantation model to evaluate the regenerative potential of scaffolds. Results: Hematoxylin and eosin, Masson, and DAPI staining indicated almost no cellular component residues in the SDS-SDC group. Histological analysis (hematoxylin and eosin staining, Masson staining), CD31 and F4/80 staining analysis, one month after implantation, revealed that the decellularized scaffolds had regenerative characteristics, and the SDS-SDC scaffold had better regenerative properties than the SDS scaffold. Conclusions: We successfully prepared the decellularized scaffold for the rat bladder by perfusion. Our results showed that the SDS-SDC scaffold had better decellularization efficiency and reconstruction ability than the SDS scaffold, which provides a new perspective on bladder reconstruction materials.

The association between recent cannabis use and urinary incontinence in women: a population-based analysis of the NHANES from 2009 to 2018.

INTRODUCTION: In this study, we investigated the association between recent cannabis use and urinary incontinence(UI) among women using the 2009-2018 National Health and Nutrition Examination Survey. METHODS: A total of 7889 women aged 20 years and older were included in the study. Respondents were dichotomized as recent users or non-users if they had used or not used cannabis in the past 30 days, respectively. Urinary incontinence (UI) was ascertained by self-report. Multivariable logistic regression models were used to adjust for sociodemographic and health-related covariates. RESULTS: Among 7889 women, 12.1% (n = 955) of subjects reported recent cannabis use. In the adjusted analysis, recent users were more likely than non-users to report stress, urge and mixed incontinence (OR 1.31, 95% CI 1.12-1.53, p < 0.001; OR 1.40, 95% CI 1.18-1.66, p < 0.001; and OR 1.29, 95% CI 1.12-1.53, p = 0.018). And, the association becomes more significant among heavy users (≥ 20 of the past 30 days) (SUI: OR 1.63, 95% CI 1.26-2.09, p < 0.001; UUI: OR 1.72, 95% CI 1.32-2.24, p < 0.001; and MUI: OR 1.64, 95% CI 1.20-2.25, p = 0.0019). CONCLUSION: Recent cannabis use was associated with an increased likelihood of stress, urge and mixed incontinence in women.

Associations Between Bacterial Vaginosis and Urgency Urinary Incontinence in Women: An Analysis of Nhanes 2001 to 2004.

OBJECTIVE: To investigate the relationship between bacterial vaginosis (BV) and urinary incontinence (UI) in American women. MATERIALS AND METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004 were merged. Self-collected vaginal swabs were used to assess BV. Urinary incontinence was determined by self-report. Multivariable logistic regression models were used to assess the association between BV and UI in American women, controlling for potential confounders. RESULTS: Overall, 31.3% of female respondents tested positive for bacterial vaginosis. Women with bacterial vaginosis were more likely to report stress urinary incontinence (SUI) (22.78% vs 17.79%), urgency urinary incontinence (UUI) (12.86% vs 7.26%) and mixed urinary incontinence (MUI) (7.35% vs 4.42%) than women without bacterial vaginosis. In the adjusted analysis, women with bacterial vaginosis had 1.47 times greater odds of urgency urinary incontinence (OR 1.47, 95% CI 1.07-2.17, P = .0160), and bacterial vaginosis did not increase the odds of stress urinary incontinence and mixed urinary incontinence in women. CONCLUSION: After controlling for known risk factors, bacterial vaginosis seems to be significantly related to female urgency urinary incontinence. However, the cross-sectional nature of this study does not allow the conclusion of causality. Further basic and cohort studies are needed to examine the association of BV with UUI.

Main Pathological Changes of Benign Ureteral Strictures.

Objective: To identify the pathological classification of benign ureteral strictures according to the histological features and explore the relationship between various pathological types and inflammatory cells, fibroblasts, and collagen. Patients and Methods: Thirty one specimens from patients diagnosed with ureteral strictures between 2013 and 2021 were included and classified according to the histopathological characteristics. The number of fibroblasts and inflammatory cells was counted, and the proportion of type I and type III collagen in ureteral stricture tissues was detected by picrosirius red staining. Results: We identified three types of benign ureteral strictures in 31 specimens: inflammatory cell infiltration (n = 10, 32%), fibroplasia (n = 14, 45%), and hyalinization (n = 7, 23%), with significant differences in obstruction history and hydronephrosis grades among the three types. The number of inflammatory cells (lymphocytes, neutrophils and eosinophils) was significantly lower in hyalinization ureteral strictures than in the other two types (p < 0.05). The number of foreign-body giant cells associated with foreign-body reactions increased significantly in suture-induced ureteral strictures (p < 0.05). Fibroplasia type had the largest number of fibroblasts, whereas the other two types had smaller numbers. The results of type I and III collagen analysis showed that type I and III collagen were the most abundant in hyalinization among all ureteral stricture types (p < 0.05). Compared to ureteral strictures, the content of type I and III collagen in atresia increased significantly (p < 0.05). Conclusion: Common pathological types of benign ureteral strictures include inflammatory cell infiltration, fibroplasia, and hyalinization. Changes in type I and III collagen, inflammatory cells, and fibroblasts in different pathological types may be related to the progression of ureteral strictures.

Teenage Childbearing as an Independent Risk Factor for Stress Urinary Incontinence in American Women.

PURPOSE: To evaluate the associations among teenage childbearing (Age at first birth<=19 years old) with later-life risk of stress and urgency urinary incontinence (SUI, UUI) in American women using nationally representative data from America. MATERIALS AND METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018 were merged to include 2673 women. The question, "How old were you at the time of your first live birth?" was used to assess teenage childbearing. Urinary incontinence was ascertained by self-report. Multivariable logistic regression models were used to assess the association between teenage childbearing and urinary incontinence in American women, controlling for potential confounders. RESULTS: Among the 2673 women with complete data, the prevalence of SUI was 27.3%, and the prevalence of UUI was 22.1%. Overall, 856 of female had given birth at or before the age of nineteen. Teenage childbearing was significantly associated with SUI (OR=1.9, 95%CI=1.5-2.3, p < 0.001), but teenage childbearing was not associated with UUI (OR=1.2, 95%CI=1.0-1.5, p = 0.0658). CONCLUSION: After controlling for known risk factors, teenage childbearing seems to be signif-icantly related to female stress urinary incontinence.

Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic ß-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic ß-cells and subsequent insulin secretion in T2DM.

Association between red cell distribution width and the risk of heart events in patients with coronary artery disease.

Red cell distribution width (RDW) has been found to be a novel prognostic biomarker in patients with coronary artery disease (CAD); however, the association between RDW and the risk of heart events in patients with CAD is yet to be fully elucidated. Thus, the aim of the present study was to determine whether an elevated RDW was associated with the Framingham risk score (FRS) in patients with CAD. Data were retrospectively collected from Affiliated Dongyang Hospital of Wenzhou Medical University (Dongyang, China). The patients had undergone a coronary angiography and their clinical data were integrated. The patients (male, 260; female, 132) were divided into two groups based on the results of the coronary angiography, namely the CAD (n=283) and control groups (n=109). The FRS was calculated for all the subjects, and complete blood count testing with biochemical measurements was performed. The mean RDW level was 13.7±1.8% in the CAD group and 13.1±1.0% in the control group, while the mean FRS was 9.0±4.9 in the CAD group and 6.4±3.9 in the control group. The RDW and FRS were significantly higher in the CAD group compared with the control group (P<0.001). No statistically significant differences were observed between the groups with regard to the hematocrit, mean corpuscular volume, platelets, glucose, urea, albumin, aspartate aminotransferase, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and N-terminal pro-brain natriuretic peptide (P>0.05). The RDW was shown to significantly correlate with the red blood cell (RBC) count (r=-0.133, P=0.029), hemoglobin level (r=-0.207, P=0.001) and TG level (r=0.226, P<0.001) within the laboratory parameters, as well as the FRS (r=0.206, P<0.001). In the stepwise multivariate linear regression, which included the RBC count, hemoglobin level, TG level and RDW, the FRS was predicted by hemoglobin (r2=0.034, P=0.001), TG (r2=0.059, P<0.001) and RDW (r2=0.030, P=0.003) parameters. Therefore, a novel association was revealed between higher levels of RDW and an elevated FRS in patients with CAD, which raises the possibility that a simple marker, RDW, may be associated with an increased risk of heart events in CAD patients.