Identification of the Immune-related lncRNA SNHG14/ miR-200a-3p/ PCOLCE2 Axis in Colorectal Cancer.

Context: Procollagen C-endopeptidase enhancer 2 (PCOLCE2) is associated with the degradation of the extracellular matrix and collagen-chain trimerization, playing a yet unexplored role in tumor prognosis. Objective: The study intended to characterize PCOLCE2's influence on colorectal cancer (CRC) using expression analysis and to investigate its prognostic potential. Design: The research team performed a genetic analysis using genetic databases, including The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), the Tumor IMmune Estimation Resource (TIMER), and LinkedOmics. Setting: The study took place at Xianyang Central Hospital, Xianyang, Shaanxi Province, China. Outcome Measures: The research team: (1) identified differentially expressed PCOLCE2; (2) determined PCOLCE2 expression in gastrointestinal neoplasm; (3) determined the relationship between PCOLCE2 expression and clinical information; (4) identified the mRNA-miRNA-lncRNA regulatory network; (5) ascertained miRNA expression regulated changes in downstream mRNA levels, that could affecting patients' overall survival (OS) and prognoses; (6) assessed the correlation between PCOLCE2 and immune cells; (7) established the relationship between PCOLCE2 and the immune checkpoint; (8) determined the correlation between PCOLCE2 and tumor purity and immune cell infiltration; (9) determined the relationship between PCOLCE2 expression and clinicopathological features; and (10) identified the pathological changes of PCOLCE2. Results: PCOLCE2 in colorectal adenocarcinoma (COAD) tissues was significantly lower than that in normal tissues (P < .05), correlating with DNA methylation and copy-number variation. Elevated PCOLCE2 levels were associated with poorer overall survival (OS), with P = 4.2e-07, and with advancing clinical stages-II, III, and IV-of the cancer (all P < .05). Furthermore, PCOLCE2 was significantly associated with the MSI phenotype and was an independent element impacting colorectal cancer's prognosis. The correlation analysis revealed positive connections between PCOLCE2 expression and immune checkpoint-linked genes-programmed cell death protein 1 (PDCD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and cluster of differentiation 274 (CD274), all while also being negatively correlated with tumor purity (Cor=-0.223, P = 5.59E-06) and positively associated with CD8+ T cells (Cor=0.087, P = 7.87E-02), CD4+T cells (Cor=0.236, P = 1.64E-06), macrophages (Cor=0.362, p=6.06E-14), neutrophils (Cor=0.206, P = 4.28E-05), B(Cor=0.231, P = 2.95E-06). Conclusions: The current study revealed for the first time that a novel regulatory axis-long noncoding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14)/ miR-200a-3p/ PCOLCE2- can act as the oncogenic axis of CRC cells and that clinicians can use it to predict the OS of colon-cancer patients. Additionally, differences in the protein expression of PCOLCE2 between normal and adenocarcinoma-colorectal tissues suggest its potential as a prognostic biomarker for CRC.

450-nm blue diode laser: a novel medical apparatus for upper tract urothelial lesions.

OBJECTIVE: To explore the feasibility, safety and effectiveness of the 450-nm blue diode laser (BL), novel blue laser in the treatment of upper tract urothelial carcinomas (UTUCs) and other lesions in a porcine model. MATERIAL AND METHODS: For in vitro experiment, the ureter tissue was vaporised and coagulated with BL, green-light laser (GL) and Ho:YAG laser (Ho). The efficiency, width and depth of vaporisation, and depth of coagulation were recorded and compared. For in vivo experiments, four swines weighing 70 kg were used. In the acute group, different modes of operations were performed to evaluate the thermal damage, perforation and bleeding. In the chronic group, the overall appearance of the ureter and laser wound healing were observed by the naked eyes and H&E staining 3 weeks after surgery. RESULTS: In in vitro study, the BL showed a higher efficiency of tissue vaporisation and less tissue coagulation for fresh ureter compared to GL and Ho. In the in vivo study, the power of BL set at 7 W was better, and the thickness of thermal damage varied with different surgery types in the range of 74-306 µm. After 3 weeks, the wound healed well static in vaporisation (SV), moving vaporisation (MV) and H&E staining indicated mucosal healing rather than scar healing. CONCLUSION: 5-10W blue diode laser achieved a higher efficiency of tissue vaporisation and less tissue coagulation in a porcine model, indicating its potential application in the endoscopic surgery of UTUC as an optional device with high performance and safety.

Dynamic Predictive Models with Visualized Machine Learning for Assessing the Risk of Lung Metastasis in Kidney Cancer Patients.

Objective: To establish and verify the clinical prediction model of lung metastasis in renal cancer patients. Method: Kidney cancer patients from January 1, 2010, to December 31, 2017, in the SEER database were enrolled in this study. In the first section, LASSO method was adopted to select variables. Independent influencing factors were identified after multivariate logistic regression analysis. In the second section, machine learning (ML) algorithms were implemented to establish models and 10-foldcross-validation was used to train the models. Finally, receiver operating characteristic curves, probability density functions, and clinical utility curve were applied to estimate model's performance. The final model was shown by a website calculator. Result: Lung metastasis was confirmed in 7.43% (3171 out of 42650) of study population. In multivariate logistic regression, bone metastasis, brain metastasis, grade, liver metastasis, N stage, T stage, and tumor size were independent risk factors of lung metastasis in renal cancer patients. Primary site and sequence number were independent protection factors of LM in renal cancer patients. The above 9 impact factors were used to develop the prediction models, which included random forest (RF), naive Bayes classifier (NBC), decision tree (DT), xgboost (XGB), gradient boosting machine (GBM), and logistic regression (LR). In 10-foldcross-validation, the average area under curve (AUC) ranked from 0.907 to 0.934. In ROC curve analysis, AUC ranged from 0.879-0.922. We found that the XGB model performed best, and a Web-based calculator was done according to XGB model. Conclusion: This study provided preliminary evidence that the ML algorithm can be used to predict lung metastases in patients with kidney cancer. This low cost, noninvasive and easy to implement diagnostic method is useful for clinical work. Of course this model still needs to undergo more real-world validation.

A Novel Nomogram for Prediction and Evaluation of Lymphatic Metastasis in Patients With Renal Cell Carcinoma.

Background: Lymphatic metastasis is an important mechanism of renal cell carcinoma (RCC) dissemination and is an indicator of poor prognosis. Therefore, we aimed to identify predictors of lymphatic metastases (LMs) in RCC patients and to develop a new nomogram to assess the risk of LMs. Methods: This study included patients with RCC from 2010 to 2018 in the Surveillance, Epidemiology, and Final Results (SEER) database into the training cohort and included the RCC patients diagnosed during the same period in the Second Affiliated Hospital of Dalian Medical University into the validation cohort. Univariate and multivariate logistic regression analysis were performed to identify risk factors for LM, constructing a nomogram. The receiver operating characteristic (ROC) curves were generated to assess the nomogram's performance, and the concordance index (C-index), area under curve value (AUC), and calibration plots were used to evaluate the discrimination and calibration of the nomogram. The nomogram's clinical performance was evaluated by decision curve analysis (DCA), probability density function (PDF) and clinical utility curve (CUC). Furthermore, Kaplan-Meier curves were performed in the training and the validation cohort to evaluate the survival risk of the patients with lymphatic metastasis or not. Additionally, on the basis of the constructed nomogram, we obtained a convenient and intuitive network calculator. Results: A total of 41837 patients were included for analysis, including 41,018 in the training group and 819 in the validation group. Eleven risk factors were considered as predictor variables in the nomogram. The nomogram displayed excellent discrimination power, with AUC both reached 0.916 in the training group (95% confidence interval (CI) 0.913 to 0.918) and the validation group (95% CI 0.895 to 0.934). The calibration curves presented that the nomogram-based prediction had good consistency with practical application. Moreover, Kaplan-Meier curves analysis showed that RCC patients with LMs had worse survival outcomes compared with patients without LMs. Conclusions: The nomogram and web calculator (https://liwenle0910.shinyapps.io/DynNomapp/) may be a useful tool to quantify the risk of LMs in patients with RCC, which may provide guidance for clinicians, such as identifying high-risk patients, performing surgery, and establishing personalized treatment as soon as possible.

Long Non-Coding RNA Signatures Associated with Ferroptosis Predict Prognosis in Colorectal Cancer.

BACKGROUND: Currently, colorectal cancer has become a common gastrointestinal malignancy that usually occurs in the colon and rectum, and ferroptosis plays a vital role in the pathology and progression of colorectal tumors. METHODS: A total of 627 patients (51 normal and 644 tumor samples) from The Cancer Genome Atlas (TCGA)-COAD and TCGA-READ were included in the study. Lasso and Cox's regression was employed to analyze the characteristic lncRNAs in colorectal cancer samples, and a distinctive prognostic model of ferroptosis-related lncRNAs was established. By analyzing the divergence between the high and low-risk groups of ferroptosis-related lncRNAs, 15 characteristic lncRNAs related to the prognosis of colorectal cancer were evaluated. Kaplan-Meier analysis, operation characteristic curve (ROC), nomogram, and gene set enrichment analyses (GSEA) further confirmed the validity of the characteristic prognostic model with ferroptosis-related lncRNAs. RESULTS: Kaplan-Meier analysis confirmed a high-risk group of ferroptosis-related lncRNA interrelated with a poor prognosis in colorectal cancer. AUC estimates of 1 -, 3 -, and 5-year survival rates for ferroptosis-related lncRNA characteristic models were 0.745, 0.767 and 0.789. GSEA analysis showed that immune and malignancy-related pathways were active in the high-risk score group. In addition, differential analyses of immune function, including Checkpoint, cytolytic, HLA, and T cell co-inhibition, differed significantly betwixt low - and high-risk groups.CD160, TNFRSF18, CD27, PDCD1, CD200R1, ADORA2A, TNFRSF14, LAIR1, CD244, CD40, TNFRSF4, CD70, TNFSF14, TNFRSF25, CD276, HHLA2, VTCN1, LAG3, TNFSF18, and other immune checkpoints had different expressions betwixt the high- and low-risk group. CONCLUSION: Fifteen kinds of lncRNAs with different expressions (AP003555.1, AC099850.3, AL031985.3, LINC01857, STPG3-AS1, AL137782.1, AC124067.4, AC012313.5, AC083900.1, AC010973.2, ALMS1-IT1, AC013652.1, AC133540.1, AP006621.2, AC018653.3) were closely associated with poor prognosis of colorectal cancer. These indicators were significantly correlated with the overall survival (OS) rate and could be used as prognostic evaluation criteria.

Global, Regional, and National Incidence and Year Lived with Disability for Benign Prostatic Hyperplasia from 1990 to 2019.

The objective of this study is to provide comprehensive and up-to-date estimates on the disease burden of BPH in 204 countries and territories between 1990 and 2019. Data about incidence, year lived with disability (YLD), and their age-standardized rates (ASRs) for 21 regions, 5 Socio-demographic Index (SDI) quintiles, 204 countries and territories, and 12 age categories from 1990 to 2019 were obtained from the Global Burden of Disease 2019 study. Estimated annual percentage changes (EAPCs) of the ASRs and the associations between SDI and the ASRs were estimated. The effects of population growth, population aging, and age-specific rate on the changes in the absolute numbers of incidence and YLD were quantified. Globally, there were 11.26 million (95% uncertainty interval [UI]: 8.79, 14.46) new cases and 1.86 million (95%UI: 1.13, 2.78) YLD due to BPH in 2019. The global ASRs of incidence (EAPC: -0.031, 95% CI: -0.050, -0.012) and YLD (EAPC: -0.058, 95% CI: -0.084, -0.031) decreased slightly from 1990 to 2019, whereas the absolute numbers increased dramatically from 1990 (incidence by 105.7% and YLD by 110.6%), mainly driven by the population growth (53.5% for incidence and 54.4% for YLD) and population aging (55.7% for incidence and 63.2% for YLD). The burden of BPH varied markedly among different regions, socioeconomic status, and countries. As the population is growing and aging, great efforts are required to develop effective prevention, treatment and management strategies to meet the high and increasing burden of BPH worldwide.

SELE gene as a characteristic prognostic biomarker of colorectal cancer.

OBJECTIVE: To investigate the expression and clinical value of the E-selectin gene (SELE) in colorectal cancer (CRC). METHODS: Using gene expression profiles and clinicopathological data for patients with CRC from The Cancer Genome Atlas, and tumor and adjacent normal tissues from 31 patients with CRC from Xianyang Central Hospital, we studied the correlation between SELE gene expression and clinical parameters using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: Higher expression of SELE was significantly associated with a poorer prognosis and shorter survival in patients with CRC. The median expression level of SELE was significantly higher in CRC tissues compared with healthy adjacent tissue. Cox regression analysis showed that the prognosis of CRC was significantly correlated with the expression of SELE. Immunohistochemical analysis also showed that positive expression of E-selectin increased significantly in line with increasing TNM stage.Conclusion: This study confirmed that SELE gene expression is an independent prognostic factor in patients with CRC.

Re-positive Cases of Nucleic Acid Tests in Discharged Patients With COVID-19: A Follow-Up Study.

Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 ± 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 ± 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients.

α1-Blockers and 5α-Reductase Inhibitors Are the Most Recommended Drugs in Treating Benign Prostatic Hyperplasia: An Evidence-Based Evaluation of Clinical Practice Guidelines.

OBJECTIVE: To systematically evaluate the quality of clinical practice guidelines (CPG) for medically treating benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application. METHODS: We searched databases of National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment to October 13, 2019, to collect evidence-based guidelines and/or consensus on BPH. Method quality of included guidelines was assessed according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, and differences and similarities among recommendations were compared. RESULTS: A total of 22 guidelines were included, of which eight were updated versions. According to the AGREE II instrument, the median score of scope and purpose, stakeholder involvement, rigor of formulate, clarity of presentation, applicability, and editorial independence was 71.5%, 41%, 25%, 64%, 18%, and 28%, respectively. Based on recommendations for medical treatment, almost all guidelines recommended α1-blockers and 5α-reductase inhibitors, and most guidelines also recommended muscarinic receptor antagonists. In terms of drug combination therapy, most guidelines recommended "α1 blockers and 5α-reductase inhibitors", and some guidelines also recommended "α1 blockers and muscarinic receptor antagonists". CONCLUSION: The recommendations from different guidelines were basically similar, only showing conflicts in some areas. The quality of included guidelines remains to be unified, and their context can provide valuable implications for development or improvement.

Extracellular regulated kinase 5 mediates osteoporosis through modulating viability and apoptosis of osteoblasts in ovariectomized rats.

Postmenopausal osteoporosis is a common condition characterized by the increase and activation of osteoclasts. The present study aimed to investigate the effects of extracellular signal-regulated kinase (ERK) 5 (ERK-5) on postmenopausal osteoporosis by regulating the biological behaviors of osteoblasts. Sprague-Dawley (SD) rats were ovariectomized to develop an osteoporosis model. A lentivirus packaging system was employed to generate lentiviruses capable of up- or down-regulating the expression of ERK-5 in ovariectomized rats. The femoral biomechanical properties, bone mineral density (BMD), contents of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) and bone turnover markers in rats, as well as viability, cycle and apoptosis of osteoblasts and ALP activity in osteoblasts were measured in the ovariectomized rats so as to explore the functional significance of ERK-5 in postmenopausal osteoporosis. The femoral mechanical strength of ovariectomized rats was enhanced by overexpression of ERK-5. Meanwhile femoral BMD, and bone metabolism were increased, and bone turnover normalized in the ovariectomized rats when ERK-5 was overexpressed. Lentivirus-mediated ERK-5 overexpression in osteoblasts was observed to inhibit osteoblast apoptosis, and promote viability, accompanied with increased ALP activity. Taken together, ERK-5 could decelerate osteoblast apoptosis and improve postmenopausal osteoporosis by increasing osteoblast viability. Thus, our study provides further understanding on a promising therapeutic target for postmenopausal osteoporosis.

A Novel 450 nm Semiconductor Blue Laser System for Application in Colon Endoscopic Surgery: An Ex Vivo Study of Laser-Tissue Interactions.

Objective: Our study aimed to detect whether 450 nm blue laser can be applied effectively and safely in endosocopic submucosal dissection (ESD) system for surgery in colonic tissue. Background data: Semiconductor blue laser has been applied in surgery due to its excellent cutting property, however, whether blue laser can be applied in colonic surgery has not been reported. Materials and methods: Porcine colon tissues were vaporized by 450 nm blue semiconductor laser at 10-25 W and at working distances from 0.5 to 3 mm, with a three-dimensional scanning system. Moreover, we designed an ESD model and applied blue laser at 10 W on porcine colonic tissues with this system. Dimensions of the vaporized tissues and coagulation zones were assessed under microscopy. Results: Since the thickness of colonic wall is no more than 1 mm, first we determined the cutting property and safety of blue laser on porcine colon tissue and found that blue laser at 10 W made lesions shallower than 1 mm and the depth of vaporization can be controlled effectively within muscularis mucosa and submucosa. Moreover, a large scale of porcine colonic tissue was vaporized precisely by blue laser at power of 10 W with the ESD system ex vivo. Conclusions: Our results indicate that 450 nm blue laser at 10 W can be well controlled for laser-tissue interaction with excellent cutting efficiency and less thermal damage in adjacent tissues especially side of the submucosa. Therefore, 450 nm semiconductor blue laser could be a safe alternative approach for colonic surgery.

A 3-Dimensional Finite Element Analysis of Adjacent Segment Disk Degeneration Induced by Transforaminal Lumbar Interbody Fusion After Pedicle Screw Fixation.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is an effective treatment of upper lumbar intervertebral disk herniation. However, its clinical efficacy for adjacent segment disk degeneration (ASDD) remains undefined. Therefore, the biomechanical evaluation of ASDD caused by TLIF after pedicle screw fixation (PSF) was explored via a 3-dimensional (3D) finite element analysis. METHODS: Computed tomography images of a healthy male adult volunteer were used in this study. A L3-4 3D finite element model (model) was successfully constructed using Pro/E software, which was also used to establish the L4-5 of the TLIF, PSF, and PSF + TLIF models. Under the same loading conditions, the protrusion and retraction of the adjacent intervertebral disk and the stress distribution of the annulus fibrosis, facet joint, and articular process in the TLIF, PSF, and PSF + TLIF models were all compared. RESULTS: Protrusion and retraction of the adjacent intervertebral disk were more notable in the PSF + TLIF model than in the PSF model under the same loading conditions. The stress of the annulus fibrosis of the PSF + TLIF model was stronger relative to that of the PSF model under flexion, extension, or lateral bending. The stress of the articular process of the PSF + TLIF model was also stronger than that of the PSF model under extension or lateral bending. CONCLUSIONS: This study provides evidence that TLIF may aggravate ASDD after PSF. Furthermore, the findings provided in this report represent the theoretic basis for the clinical analysis of ASDD caused by TLIF after PSF.

WITHDRAWN: Spleen tyrosine kinase (SYK) protects renal tubular epithelial cell against hypoxia injury in children with acute kidney injury.

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Plasma long non-coding RNA MALAT1 is associated with distant metastasis in patients with epithelial ovarian cancer.

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a newly identified metastasis-associated long non-coding RNA. In a previous study, it was identified that plasma levels of MALAT1 were significantly increased in gastric cancer patients with metastasis compared with gastric cancer patients without metastasis and healthy control individuals. However, it is unclear whether plasma levels of MALAT1 may act as a biomarker for evaluating the development of metastasis in epithelial ovarian cancer (EOC). In the present study, groups that consisted of 47 patients with EOC and metastasis (EOC/DM), 47 patients with EOC without metastasis (EOC/NDM), and 47 healthy control (HC) individuals were established. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of plasma MALAT1 in these groups. The results showed that levels of plasma MALAT1 were significantly increased in the EOC/DM group compared with the EOC/NDM and HC groups (P<0.001). Receiver operating characteristic (ROC) analysis indicated that plasma MALAT1 yielded an area under the curve (AUC) of 0.820 [95% confidence interval (CI), 0.734-0.905; P<0.001], distinguishing between EOC/DM and EOC/NDM. ROC analysis also yielded an AUC of 0.884 (95% CI, 0.820-0.949; P<0.001), with 89.4% sensitivity and 72.3% specificity for distinguishing between EOC/DM and HC. Furthermore, multivariate analysis indicated that overexpression of MALAT1, differentiation (poor), tumor-node-metastasis stage (IV), lymph node metastasis (N3), peritoneal invasion (present) and higher serum carbohydrate antigen 125 levels were independent predictors of survival (hazard ratio, 3.322; P=0.028) in patients with EOC. Kaplan-Meier analysis revealed that patients with increased MALAT1 expression had a poorer disease-free survival time. In conclusion, the levels of plasma MALAT1 may act as a valuable biomarker for the diagnosis of metastasis.