A study of recurrent life-threatening thrombosis accompanied with the duplication of the factor IX gene.

Hereditary predisposition play an important role in thrombosis, especially in younger patients. Here we studied a young patient who experienced three different episodes of severe thromboses, some of which were life-threatening (pulmonary artery thrombosis, portal and mesenteric vein thrombosis, and arterial thrombosis of the lower leg). Blood levels of clotting related indicators were assessed. We screened 35 genes linked to thrombosis. We discovered a 756 kb duplication that spanned the F9 gene in region q27.1 of the X chromosome. The repeat includes the full F9 gene, thus, the patient had two functional copies of FIX with the FIX activity 192%. An identical repetition was found in the patient's mother. Both the patient and his mother had high, but variable, plasma FIX activities that promote coagulation. The patient's frequent, severe thrombolic events maybe attributed to the duplication of a big portion of the F9 gene and lupus anticoagulant positive.

Integration of machine learning to identify diagnostic genes in leukocytes for acute myocardial infarction patients.

BACKGROUND: Acute myocardial infarction (AMI) has two clinical characteristics: high missed diagnosis and dysfunction of leukocytes. Transcriptional RNA on leukocytes is closely related to the course evolution of AMI patients. We hypothesized that transcriptional RNA in leukocytes might provide potential diagnostic value for AMI. Integration machine learning (IML) was first used to explore AMI discrimination genes. The following clinical study was performed to validate the results. METHODS: A total of four AMI microarrays (derived from the Gene Expression Omnibus) were included in bioanalysis (220 sample size). Then, the clinical validation was finished with 20 AMI and 20 stable coronary artery disease patients (SCAD). At a ratio of 5:2, GSE59867 was included in the training set, while GSE60993, GSE62646, and GSE48060 were included in the testing set. IML was explicitly proposed in this research, which is composed of six machine learning algorithms, including support vector machine (SVM), neural network (NN), random forest (RF), gradient boosting machine (GBM), decision trees (DT), and least absolute shrinkage and selection operator (LASSO). IML had two functions in this research: filtered optimized variables and predicted the categorized value. Finally, The RNA of the recruited patients was analyzed to verify the results of IML. RESULTS: Thirty-nine differentially expressed genes (DEGs) were identified between controls and AMI individuals from the training sets. Among the thirty-nine DEGs, IML was used to process the predicted classification model and identify potential candidate genes with overall normalized weights > 1. Finally, two genes (AQP9 and SOCS3) show their diagnosis value with the area under the curve (AUC) > 0.9 in both the training and testing sets. The clinical study verified the significance of AQP9 and SOCS3. Notably, more stenotic coronary arteries or severe Killip classification indicated higher levels of these two genes, especially SOCS3. These two genes correlated with two immune cell types, monocytes and neutrophils. CONCLUSION: AQP9 and SOCS3 in leukocytes may be conducive to identifying AMI patients with SCAD patients. AQP9 and SOCS3 are closely associated with monocytes and neutrophils, which might contribute to advancing AMI diagnosis and shed light on novel genetic markers. Multiple clinical characteristics, multicenter, and large-sample relevant trials are still needed to confirm its clinical value.

Identification of novel susceptibility factors related to CP/CPPS-like symptoms: Evidence from a multicenter case-control study.

BACKGROUND: We aimed to systematically identify novel susceptible factors related to the occurrence and development of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)-like symptoms that were not limited to lifestyles or dietary habits in Chinese population. METHODS: We recruited participants from three centers (Shanghai [northeast], Hefei [east], and Lanzhou [northwest]) from August 2020 to June 2021. Demographics, lifestyles, dietary habits, past medical history, and national institutes of health-chronic prostatitis symptom index (NIH-CPSI) were collected from the individuals via optimized questionnaires. Logistic regression analysis and multivariate adjustment models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the association between these variables and CP/CPPS-like symptoms. RESULTS: A total of 1851 participants were enrolled in this study (764 cases and 1087 controls). Age distributions differed between groups (median, range: 32, 18-74 vs. 29, 18-70, p < 0.001). After adjustment, physicochemical occupational hazards were identified significantly related to CP/CPPS-like symptom occurrence and development (ORoccurrence : 1.389, 95% CI: 1.031-1.870, p < 0.001; ORdevelopment : 2.222, 95% CI: 1.464-3.372, p < 0.001); besides, greater than or equal to four ejaculations per week significantly increased the likelihood of CP/CPPS-like symptoms compared with one ejaculation per week (ORoccurrence : 3.051, 95% CI: 1.598-5.827, p = 0.001). For these patients, who were easily felt gastrointestinal discomfort caused by spicy food intake, they had a higher incidence to affect with CP/CPPS-like symptoms (ORoccurrence : 2.258, 95% CI: 1.858-2.745, p < 0.001). In addition, history of drug allergy and genitourinary infections were identified as independent susceptible factors for the occurrence of CP/CPPS-like symptoms (ORoccurrence : 1.689, 95% CI: 1.007-2.834, p = 0.047; ORoccurrence : 3.442, 95% CI: 2.202-5.382, p < 0.001, respectively), while the history of rheumatic immune diseases was found tightly associated with the development of CP/CPPS-like symptoms (ORdevelopment : 2.002, 95% CI: 1.008-4.058, p = 0.048). CONCLUSION: Infection/inflammatory/immune-related disorders, novel dietary habits, and lifestyles associated with the susceptibility of CP/CPPS-like symptoms' occurrence and development are identified. Altering these irregular conditions serves as potential strategies for the treatment of patients with CP/CPPS-like symptoms.

Infiltration of inflammatory factors induced penile damage in chronic prostatitis.

The present study aimed to investigate the mechanism of penile damages in experimental autoimmune prostatitis (EAP) rat models to reveal the potential pathological mechanism of the relationship between CP and penile damages. Sprague-Dawley (SD) rats were administered with different concentrations of prostate tissue homogenate supernatant (PTHS) by multipoint subcutaneous injection to establish EAP models. IHC staining was done to assess the expression of inflammatory cytokines in prostate tissues and the corpus cavernosum of penis. Masson and Tunel staining was conducted to observe the fibrosis and apoptosis in the corpus cavernosum. Finally, the functional changes of corpus cavernosum were assessed by WB and IHC staining. The results revealed that EAP rats with different prostatitis severity were successfully established by PTHS. The expression of IL-1ß, IL-6 and TNF-α in prostate tissues increased with the concentration of PTHS. The results of Masson and Tunel staining indicated fibrosis and apoptosis gradually aggravated in corpus cavernosum among different subgroups. The function of cavernosum impaired by prostatitis from WB and IHC results and positively with the severity. In conclusion, there existed the infiltration of inflammatory factors and impaired function in the corpus cavernosum of EAP rats' penis and positively correlated with the severity of prostatitis.

MLC1 Overexpression Inhibits Tumor Progression through PI3K/AKT Signal Pathway in Prostate Cancer.

Prostate cancer (PC) is a prevalent malignancy in males, characterized by high morbidity and mortality. Despite MLC1 being established as a key mediator in tumor progression, its role in PC remains unexplored. This study aims to validate MLC1's anti-tumor effects and uncover potential mechanisms. MLC1's clinical significance is assessed using data from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. MLC1 expression is significantly reduced in PC samples compared with the adjacent normal tissues. MLC1 expression correlates negatively with tumor metastasis and positively with the survival of patients with PC. In vitro, up-regulating MLC1 effectively inhibits tumor progression by curtailing proliferation, infestation, and migration through the deactivation of the PI3K/AKT signaling pathway. Conversely, down-regulating MLC1 promotes PC progression, a phenomenon alleviated by the PI3K/AKT inhibitor, Gefitinib. Furthermore, the anti-tumor function of MLC1 is corroborated by a reduction in tumor volume compared with the negative control in vivo. This study confirms the anti-tumor effects of MLC1 via in vitro and in vivo experiments, demonstrating its potential mechanism of inhibiting the PI3K/AKT signaling pathway.

Prognostic value of preoperative combined neutrophil, monocyte, and lymphocyte scores in patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A retrospective study.

BACKGROUND: In a multi-institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy. METHODS: Between January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X-tile software to obtain the optimum cut-off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer-specific survival (CSS) in patients with RCC by Kaplan-Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C-index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time-dependent ROC curves. RESULTS: The optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M-stage (p = 0.008), T-stage (p < 0.001), N-stage (p = 0.006), and AJCC stage (p < 0.001). Multivariate Cox regression analysis revealed that RCC patients with lower PBIS scores showed a worse postoperative prognosis and served as an independent predictor of OS (p = 0.002) and CSS (p < 0.001). Ultimately, the nomograms based on PBIS scores demonstrated excellent predictive performance for OS (C-index: 0.770) and CSS (C-index: 0.828) through the analysis of calibration curves, ROC curves, DCA curves, and time-dependent ROC curves. CONCLUSION: PBIS score served as novel and effective predictor to accurately predict OS and CSS in patients with RCC receiving laparoscopic nephrectomy.

Cuproptosis-related LINC01711 promotes the progression of kidney renal clear cell carcinoma.

This study utilized The Cancer Genome Atlas (TCGA) database to identify cuproptosis-related long non-coding RNAs (CRlncRNAs) in patients with kidney renal clear cell carcinoma (KIRC) which was further applied to construct risk signatures. All KIRC patients were divided into the training and the validation sets at a ratio of 7:3. Lasso regression analysis identified two prognosis-associated CRlncRNAs (LINC01204 and LINC01711), and prognostic risk signatures were constructed in both the training and the validation sets. Kaplan-Meier survival curves showed that patients with high-risk scores had significantly shorter overall survival (OS) than those with low-risk scores both in both the training and the validation sets. The area under the curve (AUC) of the prognostic nomogram generated based on age, grade, stage and risk signature to predict the 1-, 3- and 5-year OS were 0.84, 0.81 and 0.77, respectively, and the calibration curves also showed the high accuracy of the nomogram. In addition, we constructed the LINC01204/LINC01711-miRNA-mRNA ceRNA network graph. Finally, we experimentally investigated the function of LINC01711 by knocking down LINC01711 and revealed that knockdown of LINC01711 inhibited the proliferation, migration and invasion of KIRC cells. Hence, in this study, we developed a signature of prognostic risk-associated CRlncRNAs that could accurately predict the prognosis of KIRC patients and constructed a related ceRNA network to shed light on the mechanistic study of KIRC. LINC01711 might serve as a potential biomarker for the early diagnosis and prognosis of KIRC patients.

The relationship between ethylene oxide levels in hemoglobin and the prevalence of kidney stones in US adults: an exposure-response analysis from NHANES 2013-2016.

Exposure to ethylene oxide may cause a number of diseases. The purpose of this study was to investigate whether there is an association between hemoglobin ethylene oxide (HbEO) and the risk of developing kidney stones in US adults. We analyzed 3348 patients from the National Health and Nutrition Survey (NHANES) 2013-2016 and conducted a cross-sectional study. Dose-response analysis curves of restricted cubic spline function, multiple logistic regression, and subgroup analysis were used to investigate the association between HbEO and the risk of kidney stones. Logistic regression models were used to analyze the correlation between HbEO and kidney stones. Among the 3348 participants, 3016 people self-reported having a kidney stone. After adjusting for age, sex, race, marital status, education level, diabetes, vigorous recreational activity, moderate recreational activity, body mass index, blood urea nitrogen, creatinine, eGFR, and uric acid, we found a positive association between HbEO and the risk of kidney stones. We divided patients into four groups based on quartiles of HbEO levels and performed multifactorial logistic regression after adjusting for confounders, which showed that the incidence of kidney stones increased with increasing HbEO concentrations compared with Q1 (Q2, OR = 0.922, 95% CI, 0. 657-1.295, P = 0.639; Q3, OR = 1.004, 95% CI, 0.713-1.414, P = 0.983; Q4, OR = 1.535, 95% CI, 1.114-2.114, P = 0.009). High levels of HbEO were positively correlated with the risk of kidney stone development and could be used as an indicator of kidney stone prevention.

Association between sarcopenia and kidney stones in United States adult population between 2011 and 2018.

Purpose: To investigate the relationship between kidney stones and sarcopenia in United States adult population between 2011 and 2018. Materials and methods: We conducted a cross-section study based on the National Health and Nutrition Examination Survey (NHANES) including 39,156 individuals. Sarcopenia was assessed by the sarcopenia index. Association between kidney stones and sarcopenia verified by multiple logistic regression analysis and dose-response curves analysis using restricted cubic spline (RCS) regression. Meanwhile, propensity score matching (PSM) was performed to exclude the effect of confounding variables. Results: There were 9,472 participants in the study by our accurate enrollment screening process. The odds of kidney stones decreased significantly with the increase of sarcopenia index. Logistic regression analysis showed that sarcopenia expressed significant differences in the participants which suffered kidney stone before PSM (p < 0.001). In model 4, adjusting all relevant covariates shown that adjusted odds ratio (aOR) of the 95% confidence intervals for kidney stones in all participants, age <39 years and age ≥40 years, were, respectively, 1.286 (1.006-1,643), 1.697 (1.065-2.702), and 0.965 (0.700-1.330) for sarcopenia, and p values were 0.044, 0.026, and 0.827. After performing PSM, the aOR of the 95% in modal 4 for kidney stones in all participants and age <40 year were 2.365 (1.598-3.500) and 6.793 (2.619-17.6180), respectively (p < 0.01), and especially the aOR in participants (age ≥40) was 1.771(1.138-2.757) with p value being 0.011. Conclusion: Sarcopenia was positively related to the potential risk of kidney stones in the United States adult population.

Prognostic value of total body muscle-fat ratio in patients with kidney stone disease: A US population-based study.

Purpose: To examine the relationship between the muscle-fat ratio (MFR) and kidney stone disease (KSD) in the adult population of the United States between 2011 and 2018, and whether it can be used as a predictor of KSD prognosis. Materials and methods: We conducted a cross-sectional study analysing 9326 patients from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. We analyzed all participants by sex, age, race, level of education, marital status, household income-to-poverty ratio, hypertension, diabetes, vigorous physical activity, moderate physical activity, blood urea nitrogen, creatinine, uric acid, cotinine, and MFR. Dose-response curves with a restricted cubic spline function, univariate and multifactorial logistic regression were used for the analysis of the correlation between MFR and KSD. Finally, we created predictive models based on age, race, hypertension, diabetes mellitus, cotinine and MFR. The prediction model was evaluated using calibration curves, receiver operating characteristic curves and clinical decision curves from the training and test sets. Results: Of the 9326 participants, 8582 (92%) self-reported that they did not have KSD and 744 (8%) self-reported that they had KSD. Univariate and multifactorial logistic regression showed that MFR was negatively associated with the prevalence of KSD (odds ratio [OR]: 0.770, 95% CI: 0.703-0.843; OR: 0.815, 95% CI: 0.738-0.897). Similarly, the risk of developing KSD decreased with increasing MFR as shown by the dose curves in the restricted cubic bar graphs. Furthermore, there is some accuracy (AUC = 0.652) and clinical applicability to the model we constructed based on the results of multifactorial logistic regression. Conclusion: The MFR is protective factor against the developing KSD in adults in the USA.

M6A-mediated-upregulation of lncRNA BLACAT3 promotes bladder cancer angiogenesis and hematogenous metastasis through YBX3 nuclear shuttling and enhancing NCF2 transcription.

Lymphatic metastasis is recognized as the leading manner of metastasis in bladder cancer (BLCa), but hematogenous metastasis accounts for a majority of cancer-associated deaths. The past two decades have witnessed tremendous attention in long non-coding RNAs (lncRNAs), which are a new hope for the development of targeted drug therapy for metastatic cancers; however, the underlying mechanism of lncRNAs involved in BLCa hematogenous metastasis remains to be elucidated. Here, we identified BLCa-associated transcript 3 (BLACAT3), a lncRNA, which was aberrantly upregulated in BLCa and corelated with poor prognosis of patients with muscle-invasive bladder cancer. Methodologically, m6A epitranscriptomic microarray, RNA sequencing and mass spectrometry (MS) were used to screen the key molecules of the regulatory axis. Functional assays, animal models and clinical samples were used to explore the roles of BLACAT3 in BLCa in vitro and in vivo. Mechanistically, m6A modification contributes to BLACAT3 upregulation by stabilizing RNA structure. BLACAT3 recruits YBX3 to shuttle into the nucleus, synergistically enhances NCF2 transcription, and promotes BLCa angiogenesis and hematogenous metastasis by activating downstream NF-κB signaling. Our findings will develop prognosis prediction tools for BLCa patients and discover novel therapeutic biological targets for metastatic BLCa.

The chloroplast genome of Salix floderusii and characterization of chloroplast regulatory elements.

Salix floderusii is a rare alpine tree species in the Salix genus. Unfortunately, no extensive germplasm identification, molecular phylogeny, and chloroplast genomics of this plant have been conducted. We sequenced the chloroplast (cp) genome of S. floderusii for the first time using second-generation sequencing technology. The cp genome was 155,540 bp long, including a large single-copy region (LSC, 84,401 bp), a small single-copy region (SSC, 16,221 bp), and inverted repeat regions (IR, 54,918 bp). A total of 131 genes were identified, including 86 protein genes, 37 tRNA genes, and 8 rRNA genes. The S. floderusii cp genome contains 1 complement repeat, 24 forward repeats, 17 palindromic repeats, and 7 reverse repeats. Analysis of the IR borders showed that the IRa and IRb regions of S. floderusii and Salix caprea were shorter than those of Salix cinerea, which may affect plastome evolution. Furthermore, four highly variable regions were found, including the rpl22 coding region, psbM/trnD-GUC non-coding region, petA/psbJ non-coding region, and ycf1 coding region. These high variable regions can be used as candidate molecular markers and as a reference for identifying future Salix species. In addition, phylogenetic analysis indicated that the cp genome of S. floderusii is sister to Salix cupularis and belongs to the Subgenus Vetrix. Genes (Sf-trnI, Sf-PpsbA, aadA, Sf-TpsbA, Sf-trnA) obtained via cloning were inserted into the pBluescript II SK (+) to yield the cp expression vectors, which harbored the selectable marker gene aadA. The results of a spectinomycin resistance test indicated that the cp expression vector had been successfully constructed. Moreover, the aadA gene was efficiently expressed under the regulation of predicted regulatory elements. The present study provides a solid foundation for establishing subsequent S. floderusii cp transformation systems and developing strategies for the genetic improvement of S. floderusii.

Constructing a heparin-modified penile decellularized scaffold to improve re-endothelialization in organizational reconstruction.

Background: Due to the unique anatomy and complex function of the penis, the reconstruction of penile defect is fraught with great challenges. The current standard methods are limited by numerous complications and insufficient donor sites. While functional vascularized penile tissue engineering offers a novel way to address this problem, revascularization remains the primary concern. Methods: In this study, a penile scaffold with associated modifications was constructed. The performance of decellularized penile scaffolds (DPSs) was improved by conjugation with heparin (HEP) and reseeding with human umbilical vein endothelial cells (HUVECs). There were three groups according to the modifications, including native DPSs, HEP-DPSs, HEP-HUVECs-DPSs. After perfusing with 1% Triton X-100/0.1% ammonium hydroxide solution, the cellular components were removed. Subsequently, the covalent binding of heparin in the DPSs was performed with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide, followed by reseeding with HUVECs. Scaffolds were implanted into the backs of rats and the implanted tissues were harvested at 1, 2, 3, and 4 weeks. Then hematoxylin and eosin (H&E) staining and immunofluorescence assays were performed to assess the degree of angiogenesis. Results: The native DPSs retained the extracellular matrix and heparinized modification. The H&E results indicated that more HUVECs covered the inner surface of tubular structures in the HEP-DPSs group compared to the native DPSs group. The number of vessels in the HEP-HUVECs-DPSs was significantly increased compared to the control scaffolds at all time points. Conclusions: These results suggested that, compared to the native DPS, heparin-conjugated scaffolds provided a superior environment for the growth of HUVECs and the modified methods provided a perspective for overcoming the obstacles in tissue engineering of transplantable penile tissues and the establishment of a functional vasculature.

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant kidney tumors with a poor prognosis. Accumulating evidence proves that zinc finger protein 268 (ZNF268) is associated with tumor progression, but the detailed regulatory functions of ZNF268 in ccRCC require further exploration. Thus, here we aim to characterize the role of ZNF268 in ccRCC. The clinical significance of ZNF268 was evaluated using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Subsequently, tumor-infiltrating immune cells, as well as upstream noncoding RNAs (ncRNAs) related to the tumor-suppressing function of ZNF268, were identified by in silico analyses. The expression of ZNF268 was significantly decreased in ccRCC samples compared with adjacent normal tissues. In addition, ZNF268 expression was negatively correlated with tumor progression and positively correlated with overall and disease-specific survival. TCGA and GTEx databases proved the potential tumor-suppressing function, which was measured both in vitro and in vivo after ZNF268 over-expression. Overexpression of ZNF268 effectively inhibited the proliferation, migration, invasion and promotied apoptosis of the Caki-1. The level of ZNF268 was positively related to the immune cell infiltration in the tumor. Moreover, we determined that the AC093157.1/miR-27a-3p axis can potentially regulate ZNF268 function in ccRCC. Our work describes a novel ncRNA-mediated ZNF268 function in ccRCC. ZNF268 acts as a tumor suppressor, and it is associated with apoptosis and immune cell infiltration in ccRCC.

Identification of prognostic factors for predicting survival of patients with malignant adrenal tumors: A population-based study.

Background: This study aimed to identify the prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in patients with malignant adrenal tumors and establish a predictive nomogram for patient survival. Methods: The clinical characteristics of patients diagnosed with malignant adrenal tumors between 1988 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. As the external validation set, we included 110 real-world patients from our medical centers. Univariate and multivariate Cox regressions were implemented to determine the prognostic factors of patients. The results from Cox regression were applied to establish the nomogram. Results: A total of 2,206 eligible patients were included in our study. Patients were randomly assigned to the training set (1,544; 70%) and the validation set (662; 30%). It was determined that gender, age, marital status, histological type, tumor size, SEER stage, surgery, and chemotherapy were prognostic factors that affected patient survival. The OS prediction nomogram contained all the risk factors, while gender was excluded in the CSS prediction nomogram. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) indicated that the nomogram had a better predictive performance than SEER stage. Moreover, the clinical impact curve (CIC) showed that the nomograms functioned as effective predictive models in clinical application. The C-index of nomogram for OS and CSS prediction was 0.773 (95% confidence interval [CI]: 0.761-0.785) and 0.689 (95% CI: 0.675-0.703) in the training set. The calibration curves exhibited significant agreement between the nomogram and actual observation. Additionally, the results from the external validation set also presented that established nomograms functioned well in predicting the survival of patients with malignant adrenal tumors. Conclusions: The following clinical variables were identified as prognostic factors: age, marital status, histological type, tumor size, SEER stage, surgery, and chemotherapy. The nomogram for patients with malignant adrenal tumors contained the accurate predictive performance of OS and CSS, contributing to optimizing individualized clinical treatments.

Multiple-model machine learning identifies potential functional genes in dilated cardiomyopathy.

Introduction: Machine learning (ML) has gained intensive popularity in various fields, such as disease diagnosis in healthcare. However, it has limitation for single algorithm to explore the diagnosing value of dilated cardiomyopathy (DCM). We aim to develop a novel overall normalized sum weight of multiple-model MLs to assess the diagnosing value in DCM. Methods: Gene expression data were selected from previously published databases (six sets of eligible microarrays, 386 samples) with eligible criteria. Two sets of microarrays were used as training; the others were studied in the testing sets (ratio 5:1). Totally, we identified 20 differently expressed genes (DEGs) between DCM and control individuals (7 upregulated and 13 down-regulated). Results: We developed six classification ML methods to identify potential candidate genes based on their overall weights. Three genes, serine proteinase inhibitor A3 (SERPINA3), frizzled-related proteins (FRPs) 3 (FRZB), and ficolin 3 (FCN3) were finally identified as the receiver operating characteristic (ROC). Interestingly, we found all three genes correlated considerably with plasma cells. Importantly, not only in training sets but also testing sets, the areas under the curve (AUCs) for SERPINA3, FRZB, and FCN3 were greater than 0.88. The ROC of SERPINA3 was significantly high (0.940 in training and 0.918 in testing sets), indicating it is a potentially functional gene in DCM. Especially, the plasma levels in DCM patients of SERPINA3, FCN, and FRZB were significant compared with healthy control. Discussion: SERPINA3, FRZB, and FCN3 might be potential diagnosis targets for DCM, Further verification work could be implemented.

Relationship between exposure to cadmium, lead, and mercury and the occurrence of urinary incontinence in women.

Cadmium, lead, and mercury are nephrotoxic metals that are commonly found as hazardous pollutants in many areas of the USA. We examined the relationship between exposure to cadmium, lead, and mercury with the occurrence of urgency urinary incontinence (UUI) and stress urinary incontinence (SUI) in women. This study was conducted using data on women > 20 years of age, collected between 2005 and 2016, who reported experiencing urinary incontinence in the National Health and Nutrition Examination Survey (NHANES). Restricted cubic spline analysis was used to characterize a dose-response relationship between continuous exposure to different nephrotoxic metals and the occurrence of UUI and SUI. A total of 4406 women were included in this study, with 2624 (59.6%) suffering from SUI and 3177 (72.1%) suffering from UUI in the weighted population. The results of our multivariate analysis indicated that age, race, marital status, body mass index (BMI), and exposure to nephrotoxic metals were risk factors for developing UI. The odds ratio (OR; 95% confidence interval) for developing UI was positively correlated with the exposure to cadmium and lead in women. The OR of SUI occurrence increased with increasing levels of cadmium in blood, with a peak at 4 µg/L. The OR of UUI occurrence increased with increasing levels of blood and urinary lead, with peaks at 7 µg/dL and 5 µg/L, respectively. The presence of mercury was not significantly correlated with the occurrence of SUI or UUI. Exposure to high levels of cadmium and lead, which are nephrotoxic metals, is associated with the occurrence of UI in women.

Prognostic value of glucose to lymphocyte ratio for patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A multi-institutional, propensity score matching cohort study.

Background: We evaluated the prognostic value of preoperative blood glucose to lymphocyte ratio (GLR) in renal cell carcinoma (RCC) patients who underwent laparoscopic nephrectomy through a multi-institutional clinical study. Methods: A total of 420 patients with RCC from three medical centers from 2014 to 2019 were included in this study. The effect of GLR on overall survival (OS) and cancer-specific survival (CSS) in RCC patients was assessed by Kaplan-Meier survival curves, univariate and multivariate Cox regression analysis. Moreover, a 1:1 propensity score matching (PSM) analysis of different GLR groups was utilized to further confirm the prognostic ability of GLR. Results: The optimal cut-off value for GLR was 6.8. Patients were divided into high GLR and low GLR groups according to the optimal cut-off value. GLR was significant association with diabetes, cardiovascular disease and AJCC stage. High GLR predicted adverse OS ( P = 0.002) and CSS ( P < 0.01) in RCC patients. Multivariate Cox regression analysis revealed that high GLR was an independent prognostic factor for OS [hazard ratio (HR): 2.389, 95% confidence interval (CI), 1.136-5.027, P = 0.008] and CSS (HR: 3.474, 95% CI, 1.555-7.761, P = 0.002). After PSM analysis of the patients in the high GLR and low GLR groups, high GLR still predicted poor OS ( P = 0.021) and CSS ( P = 0.037). Conclusions: High GLR is associated with adverse prognosis in RCC patients, and GLR can serve as an independent prognostic marker for OS and CSS in RCC patients receiving laparoscopic nephrectomy.

Prognostic Value of Lymphocyte-C-Reactive Protein Ratio in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Population-Based Study.

PURPOSE: This study aimed to assess the prognostic value of the lymphocyte-C-reactive protein ratio (LCR) in patients with bladder cancer (BCa) who underwent radical cystectomy (RC). MATERIALS AND METHODS: BCa patients between 2009 and 2018 were retrieved from our medical center. The predictive value of LCR on survival of BCa patients was evaluated through the Kaplan-Meier survival and receiver operating characteristic (ROC) curves. The multivariate Cox regression results were used for conducting the nomogram, which were further verified by ROC, decision curve analysis (DCA), and calibration curves. Propensity score matching (PSM) was performed to validate our findings. RESULTS: A total of 201 BCa patients who received RC were included in this study, with 62 (30.8%) patients in the low LCR group and 139 (69.2%) in the high LCR group. Multivariate analysis results revealed that the high LCR group was significantly related to better prognosis and functioned as a prognostic biomarker for overall survival (OS) [hazard ratio (HR) = 0.41, 95% CI, 0.26-0.66; p < 0.001] and disease-free survival (DFS) [HR = 0.40, 95% CI, 0.26-0.66; p < 0.001]. The nomogram processed better predictive capability and accuracy than TNM stage from ROC results (AUC = 0.754 vs. AUC = 0.715), with the confirmation of calibration curves and DCA. The result of PSM confirmed that LCR was significantly correlated with OS and DFS. CONCLUSION: Our finding demonstrates that LCR is a novel, convenient, and effective predictor that may provide vital assistance for clinical decision and individualized therapy in BCa patients after RC.

Combination of C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio as a Novel Prognostic Index in Patients With Bladder Cancer After Radical Cystectomy.

BACKGROUND: Inflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC). MATERIALS AND METHODS: BC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves. RESULTS: Of the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538-3.993, p < 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667-4.762, p < 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms. CONCLUSION: C-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.