Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade.

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.

Dual Improvement in Sensitivity and Humidity Tolerance of a NO2 Sensor Based on 3-Aminopropyltriethoxysilane Self-Assembled Monolayer-Functionalized SnSe2 for Explosive Photolysis Gas Detection.

Explosives can be analyzed for their content by detecting the photolytic gaseous byproducts. However, to prevent electrostatic sparking, explosives are frequently preserved in conditions with low temperatures and high humidity, impeding the performance of gas detection. Thus, it has become a research priority to develop gas sensors that operate at ambient temperature and high humidity levels in the realm of explosive breakdown gas-phase detection. In this work, 3-aminopropyltriethoxysilane (APTES) self-assembled monolayer-functionalized tin diselenide (APTES-SnSe2) nanosheets were synthesized via a facile solution stirring strategy, resulting in a room-temperature NO2 sensor with improved sensitivity and humidity tolerance. The APTES-SnSe2 sensor with moderate functionalization time outperforms the pure SnSe2 sensor in terms of the response value (317.51 vs 110.98%) and response deviation (3.11 vs 24.13%) under humidity interference to 500 ppb NO2. According to density functional theory simulations, the stronger adsorption of terminal amino groups of the APTES molecules to NO2 molecules and stable adsorption energy in the presence of H2O are the causes of the improved sensing capabilities. Practically, the APTES-SnSe2 sensor achieves accurate detection of photolysis gases from trace nitro explosives octogen, pentaerythritol tetranitrate, and trinitrotoluene at room temperature and various humidity levels. This study provides a potential strategy for the construction of gas sensors with high responsiveness and antihumidity capabilities to identify explosive content in harsh environments.

Analysis of the efficacy and risk factors of surgical treatment of recurrent UPJO in adults.

BACKGROUND: To compare the efficacy of secondary pyeloplasty and balloon dilation and to analyze the risk factors for secondary surgical failure in patients with recurrent uretero-pelvic junction obstruction (UPJO). METHODS: We retrospectively analyzed 65 patients with recurrent UPJO who underwent secondary surgery between September 2011 and March 2019, of whom 33 had complete baseline data and follow-up data. General clinical information, perioperative data, and follow-up results were collected from patients. Risk factors for surgical failure in patients with recurrent UPJO were analyzed using logistic regression. RESULTS: The failure rates of secondary pyeloplasty and balloon dilation in secondary surgery were 16.7% and 33.3%, respectively. Univariate analysis showed that ureteral stenosis length and operative time were associated with secondary pyeloplasty and balloon dilatation failure (p < 0.05), and ureteral stenosis length was an independent risk factor for secondary pyeloplasty failure (OR = 0.074, 95% CI: 0.006-0.864, p = 0.038). In the balloon dilation group, treatment failure rates were significantly lower in patients with stenotic segment lengths less than 1 ± 0.32 cm than in patients with stenotic segment lengths greater than 1 ± 0.32 cm (p = 0.019). CONCLUSIONS: The secondary pyeloplasty may provide better benefit. Ureteral stricture length is an independent risk factor for failure of secondary pyeloplasty and a potential risk factor for balloon dilatation. Operation time is a potential risk factor for pyeloplasty and balloon dilatation.

A Novel Preoperative Prediction Model Based on Deep Learning to Predict Neoplasm T Staging and Grading in Patients with Upper Tract Urothelial Carcinoma.

Objectives: To create a novel preoperative prediction model based on a deep learning algorithm to predict neoplasm T staging and grading in patients with upper tract urothelial carcinoma (UTUC). Methods: We performed a retrospective cohort study of patients diagnosed with UTUC between 2001 and 2012 at our institution. Five deep learning algorithms (CGRU, BiGRU, CNN-BiGRU, CBiLSTM, and CNN-BiLSTM) were used to develop a preoperative prediction model for neoplasm T staging and grading. The Matthews correlation coefficient (MMC) and the receiver-operating characteristic curve with the area under the curve (AUC) were used to evaluate the performance of each prediction model. Results: The clinical data of a total of 884 patients with pathologically confirmed UTUC were collected. The T-staging prediction model based on CNN-BiGRU achieved the best performance, and the MMC and AUC were 0.598 (0.592-0.604) and 0.760 (0.755-0.765), respectively. The grading prediction model [1973 World Health Organization (WHO) grading system] based on CNN-BiGRU achieved the best performance, and the MMC and AUC were 0.612 (0.609-0.615) and 0.804 (0.801-0.807), respectively. The grading prediction model [2004 WHO grading system] based on BiGRU achieved the best performance, and the MMC and AUC were 0.621 (0.616-0.626) and 0.824 (0.819-0.829), respectively. Conclusions: We developed an accurate UTUC preoperative prediction model to predict neoplasm T staging and grading based on deep learning algorithms, which will help urologists to make appropriate treatment decisions in the early stage.

Clinical outcome comparison of laparoscopic radical antegrade modular pancreatosplenectomy vs. laparoscopic distal pancreatosplenectomy for left-sided pancreatic ductal adenocarcinoma surgical resection.

Background: Laparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS) is a validated surgical treatment for patients with left-sided pancreatic ductal adenocarcinoma (PDAC). In addition, laparoscopic distal pancreatectomy (LDPS) has purported benefits. However, there is a limited analysis comparing the results between LRAMPS and LDPS. Thus, this study aims to compare the short-term and long-term outcomes of patients who underwent LRAMPS and LDPS for PDAC treatment. Methods: Patients with left-sided PDAC that underwent LRAMPS or LDPS from 2015 to 2021 were retrospectively identified. Demographic and clinic pathologic data were collected. Disease-free survival (DFS) and overall survival (OS) probabilities were obtained. Results: The number of lymph nodes retrieved was significantly greater in the LRAMPS group than in the LDPS group. Several clinicopathological factors, including CA19-9 levels greater than 37 U/ml, positive lymph nodes, moderate to poor tumor differentiation, and peripancreas fat invasion, were associated with DFS. Moderate with poor tumor differentiation was associated with poor DFS (HR 0.568; 95% CI 0.373-0.921; P = 0.021). Levels of CA19-9 greater than 37 U/ml, CEA levels greater than 5 µg/ml, larger tumor size, positive lymph nodes, moderate with poor tumor differentiation, peripancreas fat invasion, and adjuvant chemotherapy were all associated with OS. LRAMPS nearly improved OS but did not reach statistical significance. Serum carcinoembryonic antigen (CEA) levels greater than 5 ug/ml (HR 1.693; 95% CI 1.200-1.132; P = 0.001), and positive lymph nodes (HR 2.410; 95% CI 1.453-3.995; P = 0.001) were independently associated with poor OS. Treatment with adjuvant chemotherapy was associated with improved OS (HR 0.491; 95% CI 0.248-0.708; P = 0.001). Conclusions: The LRAMPS procedure achieved comparable results to standard LDPS in terms of postoperative outcomes. Treatment with chemotherapy is important for the prognosis of patients with left-sided pancreatic cancer.

Identification of Germline Mutations in Upper Tract Urothelial Carcinoma With Suspected Lynch Syndrome.

Objective: Whole-exon sequencing (WES) is a commercially available tool for hereditary disease testing. However, little is known about hereditary upper-tract urothelial carcinoma (UTUC) in the Chinese population. This study aims to investigate the prevalence of Lynch syndrome (LS) in UTUC patients with high-risk features and identify the germline mutations of genetic predisposition gene mutations in those patients. Methods: In total, 354 consecutive UTUC patients undergoing surgery were universally recruited, of whom 108 patients under 60 years old or with a personal/family history of cancer underwent universal immunohistochemistry staining to detect the expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Patients with deficient or weak MMR protein staining or meeting the Amsterdam II criterion were defined as suspected LS patients, who further experienced microsatellite instability (MSI) (BAT25, BAT26, BAT40, D2S123, D5S346, D17S250) detection and performed WES analysis to explore germline pathogenic/likely pathogenic (P/LP) alterations. Results: Of 108 patients, 90 (83.3%) cases were included due to younger than 60 years, and 18 cases due to personal/family history. IHC staining identified 21 patients with deficient MMR protein staining and 15 cases with weak MMR protein staining. Three cases met the Amsterdam II criterion but with proficient MMR protein staining. Finally, WES analysis was performed in 38 suspected LS patients and P/LP germline mutations were identified in 22 individuals. Genetic testing confirmed 5 LS cases, including 3 cases with novel mutations. MSI-harboring tumor was discovered in 4 LS cases, one of whom had weak MMR protein staining. Germline P/LP variants in DNA damage repair genes were found in 11 cases. In addition, we found that 11 patients had high- or moderate- penetrance P/LP mutations other than MMR genes. The common P/LP variants in high- or moderate-penetrance genes were 4 in ATM, 3 in MSH6 and KIT, and 2 in APC, NF1 and DICER. Conclusions: We identified approximately 11% of UTUC cases as suspected LS and at least 1.4% patients with confirmed LS-associated UTUC. In addition, broader germline genetic testing could be considered to screen for cancer severity in hereditary UTUC patients.

A self-powered photoelectrochemical cathodic molecular imprinting sensor based on Au@TiO2 nanorods photoanode and Cu2O photocathode for sensitive detection of sarcosine.

Quantitative determination of sarcosine (SAR) in biological liquids is of great importance, as SAR has been recently suggested as a promising biomarker for prostate cancer diagnostics. Herein, a self-powered photoelectrochemical (PEC) molecular imprinted sensor integrated with photoanode (Au@TiO2 nanorods) and photocathode (Cu2O) is proposed for the first time towards the specific and sensitive detection of SAR. With the benefits of strong photocurrent driving force attributed to a large inherent deviation between the Fermi levels of photoanode and photocathode in this system, the photogenerated electrons of Au@TiO2 can rapidly transferred along the outer circuit and attracted by the holes in the valence band of the photocathode, forming a self-powered PEC system and improve the photocurrent of the cathode. Under the optimal conditions, the constructed cathode imprinted sensor has a linear range of 10 nM - 10 µM, and the limitation of detection is 0.19 nM. This work proved that the PEC sensing platform has great potential in the field of miniaturized biosensing without external power supply.

NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer.

The high incidence and vulnerability to recurrence of bladder cancer (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in BLCA has not been elucidated. In this study, NFE2L3 expression was significantly increased in BLCA samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival and metastasis-free survival in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited BLCA cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition in BLCA cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

Patient-Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening.

Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient-derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient-derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine.

Threshold switching memristor-based stochastic neurons for probabilistic computing.

Biological neurons exhibit dynamic excitation behavior in the form of stochastic firing, rather than stiffly giving out spikes upon reaching a fixed threshold voltage, which empowers the brain to perform probabilistic inference in the face of uncertainty. However, owing to the complexity of the stochastic firing process in biological neurons, the challenge of fabricating and applying stochastic neurons with bio-realistic dynamics to probabilistic scenarios remains to be fully addressed. In this work, a novel CuS/GeSe conductive-bridge threshold switching memristor is fabricated and singled out to realize electronic stochastic neurons, which is ascribed to the similarity between the stochastic switching behavior observed in the device and that of biological ion channels. The corresponding electric circuit of a stochastic neuron is then constructed and the probabilistic firing capacity of the neuron is utilized to implement Bayesian inference in a spiking neural network (SNN). The application prospects are demonstrated on the example of a tumor diagnosis task, where common fatal diagnostic errors of a conventional artificial neural network are successfully circumvented. Moreover, in comparison to deterministic neuron-based SNNs, the stochastic neurons enable SNNs to deliver an estimate of the uncertainty in their predictions, and the fidelity of the judgement is drastically improved by 81.2%.

lncRNA-UCA1 in the diagnosis of bladder cancer: A meta-analysis.

BACKGROUND: The main purpose of this study is to systematically evaluate the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, and to provide a scientific basis for the diagnosis of bladder cancer. METHODS: By searching PubMed, Web of Science, EMBASE, CNKI, Wanfang, Weipu and other databases, in order to collect relevant literature of lncRNA-UCA1 for diagnosis of bladder cancer. The starting and ending time of the search is from the establishment of the database to December 31, 2019. Screen documents and extract data according to inclusion and exclusion criteria. QUADAS entry tool was used to evaluate the quality of literature. Meta-Disc 1.4 and Stata 12.0 software were used for statistical analysis, and UCA1 was combined for the statistics of bladder cancer diagnosis. RESULTS: A total of 7 articles were included in this study, including 954 cases of bladder cancer patients and 482 cases of non-bladder cancer patients. The receiver operating characteristic curve (ROC) curve AUC of lncRNA-UCA1 used to diagnose bladder cancer was 0.86. The sensitivity was 0.83 (95% CI: 0.80-0.85), and the specificity was 0.86 (95% CI: 0.82-0.89). The positive likelihood ratio is 6.38 (95% CI: 3.01-13.55), and the negative likelihood ratio is 0.20 (95% CI: 0.13-0.31). The diagnostic odds ratio is 33.13 (95% CI: 11.16-98.33). CONCLUSION: lncRNA-UCA1 has a high value of clinical auxiliary diagnosis for bladder cancer, and it can be further promoted and applied clinically.

ß-Edorphin predict pregnancy outcome of PCOS and DOR women after IVF-ET.

PURPOSE: The present study aims to explore whether ß-EP in serum (sß-EP) and follicular fluid (ffß-EP) could predict the in vitro fertilization (IVF) outcomes of patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR). METHODS: 90 PCOS women, 50 DOR women, and 100 women with normal ovarian function (control group), who were all undergoing an IVF-embryo transfer trial, were included in the study. Biochemical characteristics, anti-Mullerian hormone (AMH), sß-EP, ffß-EP, embryo formation, and pregnancy indicators were assessed in all women. The correlations of AMH and ß-EP with oocyte quality were analyzed. Population-based and age-category stratified receiver operating characteristic (ROC) curve analysis of AMH and ß-EP for predicting pregnancy and live birth were performed. RESULTS: Compared with the control group, the PCOS group had higher antral follicle count, testosterone, luteinizing hormone, AMH, sß-EP, and ffß-EP, which were lower in the DOR group. Meanwhile, the PCOS and DOR groups had higher cycle cancellation and miscarriage rates, and lower high quality embryo numbers. Correlation analysis showed that the oocyte quality were positively correlated with AMH, sß-EP, and ffß-EP. The population-based and age-stratified ROC curve analysis showed that sß-EP and ffß-EP had high sensitivity and specificity to predict pregnancy and live birth. Meanwhile, age-stratified AMH enhanced the sensitivity for prediction of live birth after IVF. CONCLUSION: sß-EP and ffß-EP are different among women with PCOS, DOR, and normal ovarian function. ß-EP can be used as a good predictor of clinical pregnancy and live birth after IVF.

Prognostic autophagy model based on CASP4 and BIRC5 expression in patients with renal cancer: independent datasets-based study.

The purpose of this study was to identify key autophagy-related genes (ARGs) in patients with renal cancer (RC) by bioinformatics analysis, and to clarify their potential prognostic value. Thirty-eight differentially expressed ARGs were identified between RC and normal tissues based on The Cancer Genome Atlas database. Functional enrichment analysis suggested that autophagy may play a tumor-promoting role in the initiation of RC. We established a prognostic model with two ARGs (CASP4 and BIRC5) demonstrating significant correlations in expression levels with patient overall survival (OS). Multivariate Cox regression analysis showed that age and the autophagy genes prognostic model were independent prognostic factors for patients with RC. Considering the known prognostic significance of clinical stage in RC, we constructed a nomogram based on age, clinical stage, and the prognostic model. The prognostic model was verified in a separate validation set and external cohort of patients from Beijing Hospital. Patients of low and high risk were defined based on the median risk value calculated by the model and the high risk appeared associated with a significant shorter OS (P < 0.01). Overall, our findings reveal that ARGs have potential prognostic value in patients with RC, providing new directions for targeted therapy.

Balloon versus Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy: a systematic review and meta-analysis.

OBJECTIVE: To compare the safety and efficacy of balloon and Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy (PCNL). METHOD: EMBASE, PUBMED, MEDLINE and the Cochrane Central Register of Controlled Trials were searched for pertinent studies up until 30 October 2019. Pooled effects were calculated as ORs with 95% CIs or mean differences (MD) with 95% CIs. Endpoints included postoperative decrease in haemoglobin, transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, access time, total operation time and length of postoperative hospitalisation (LPH). Bonferroni's correction was intercalated to reduce the likelihood of making a meta-analytical false positive. RESULTS: One randomised controlled trial and five controlled clinical trials were included, which involved 1317 patients in total. We found a lower drop in postoperative haemoglobin for patients receiving balloon dilation compared with those in the Amplatz group (MD=-0.21, 95% CI -0.33 to 0.09, p=0.0005; Bonferroni correction a=0.005). Access time in the balloon group was also, on average, 2.61 min shorter than the Amplatz group (MD=-2.61, 95% CI -4.20 to 1.01, p=0.001; Bonferroni correction a=0.005). No significant differences were identified between the two dilation methods in terms of transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, total operation time and LPH. CONCLUSION: Balloon dilation is a safe and effective tract dilation technique for access creation during fluoroscopically guided PCNL. Both of methods have similar success rates although balloon dilation is associated with significantly less postoperative haemoglobin decline and shorter access time. Therefore, balloon dilation appears to be the superior tract dilation technique, but further confirmatory research is required to confirm these findings.

MIR-138-5P inhibits the progression of prostate cancer by targeting FOXC1.

BACKGROUND: Studies have suggested that micro-RNAs (miRNAs) can function as an oncogene or a tumor suppressor in cancers. However, the role of MIR-138-5P (613394) in prostate cancer (PCa) remains unclear. METHODS: Expression level of MIR-138-5P in PCa cell lines and normal cell line was analyzed with the quantitative real-time PCR method. Cell counting kit-8 assay, colony formation assay, wound-healing assay, and transwell invasion assay were performed to analyze the biological functions of MIR-138-5P. RESULTS: We showed MIR-138-5P expression level was significantly decreased in PCa cell lines compared with the normal cell line. Overexpression of MIR-138-5P inhibits PCa cell proliferation, colony formation, cell migration, and cell invasion in vitro. Mechanistically, we showed Forkhead box C1 (FOXC1, 601090) was a direct target for MIR-138-5P in PCa. We confirmed that overexpression of FOXC1 partially reversed the effects of MIR-138-5P on PCa cell behaviors. CONCLUSIONS: Collectively, we showed that MIR-138-5P functions as a tumor suppressor gene in PCa via targeting FOXC1.

LncRNA LOXL1-AS1 promotes endometrial cancer progression by sponging miR-28-5p to upregulate RAP1B expression.

BACKGROUND: Increasing lncRNAs are found to be involved in the biological process of multiple cancer types. Herein, we aimed to reveal the role of LOXL1-AS1 in endometrial cancer (EC) progression. METHODS: Tumor and corresponding normal tissues were obtained from EC patients. Si-LOXL1-AS1 and miR-28-5p inhibitor were transfected to downregulate the expressions of LOXL1-AS1 and miR-28-5p, while miR-28-5p mimics were used to upregulate the miR-28-5p expression. CCK-8 and colony assays were applied to estimate the cell proliferation. Flow cytometry was performed to measure the cell apoptosis. Wound healing and transwell assays were conducted to assess the cell migration and invasion abilities. Informatics analysis was used to explore the relationship among LOXL1-AS1, miR-28-5p and RAP1B. RESULTS: LOXL1-AS1 was found markedly up-regulated in EC tissues and cell lines. LOXL1-AS1 knockdown displayed evident suppression in cell proliferation, migration and invasion, as well as promotion in cell apoptosis. Moreover, the LOXL1-AS1 induced regulatory effects on EC cells were partially reversed by miR-28-5p inhibitor. Mechanistically, LOXL1-AS1 competitively bond to miR-28-5p, resulting in upregulation of RAP1B. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSIONS: In summary, LOXL1-AS1 exerted oncogenic roles in EC progression by sponging miR-28-5p and thereby upregulating RAP1B. This finding might provide potential targets for EC therapy.

Caspase 4 Overexpression as a Prognostic Marker in Clear Cell Renal Cell Carcinoma: A Study Based on the Cancer Genome Atlas Data Mining.

The dysregulation of caspase 4 (CASP4) expression is related to the occurrence, development, and outcome of many malignant tumors; however, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Herein, we investigated the expression of CASP4 in tumor tissues and its relationship with clinical prognosis, immune infiltration, and drug sensitivity status of ccRCC patients. Oncomine and The Cancer Genome Atlas (TCGA) databases were used to determine CASP4 mRNA expression in ccRCC patients. The correlation between CASP4 expression and disease prognosis was evaluated using Kaplan-Meier analysis. Related pathways were obtained from TCGA database via gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Meanwhile, genes co-expressing with CASP4 in ccRCC were investigated. Finally, we analyzed the proportion of tumor-infiltrating immune cells (TICs) using the CIBERSORT computational method and assessed CASP4 methylation and its relationship with drug sensitivity. Immunohistochemical analysis of 30 paired ccRCC and adjacent normal tissues confirmed the in silico results. CASP4 mRNA expression in ccRCC was significantly higher than that in the normal tissues, positively correlated with clinicopathological features (clinical stage and pathological grade), and negatively correlated with patient overall survival (OS). GSEA and GSVA showed that the genes in the CASP4-high expression group were primarily enriched in immune-related activities. Moreover, CIBERSORT analysis of TIC proportions revealed that activated CD4 memory T cells were positively correlated with CASP4 expression. Notably, methylation analysis revealed that the abnormal upregulation of CASP4 might be caused by hypomethylation. Finally, we found that the abnormal expression of CASP4 may be related to tumor drug resistance. Overall, our study shows that CASP4 is overexpressed in ccRCC and is an important factor affecting disease prognosis. Hence, CASP4 may serve as a potential prognostic biomarker and therapeutic target in ccRCC.

MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression.

MicroRNA-34a (miR-34a) serves as a tumor suppressor in a number of different types of cancer. The present study was performed to investigate the involvement of miR-34a in bladder cancer. In the present study, miR-34a was downregulated in patients with bladder cancer compared with the healthy controls in bladder biopsies and plasma. Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size. Transfection of miR-34a mimics upregulated the expression of phosphatase and tensin homolog (PTEN) in bladder cancer cells, and decreased cell migration and invasion. miR-34a may inhibit bladder cancer cell migration and invasion by upregulating PTEN. miR-34a may additionally serve as a potential therapeutic target for bladder cancer.

One-shot dilation versus serial dilation technique for access in percutaneous nephrolithotomy: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to systematically review the outcomes of the use of one-shot dilation (OSD) and serial tract dilation for percutaneous nephrolithotomy (PCNL). METHODS: A systematic review and meta-analysis was conducted. The randomised controlled trials (RCTs) included in the study were identified from EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials. The last search was performed on 30 April 2018. Summary effects were calculated as risk ratios (RRs) with 95% CIs or mean differences (MDs) with 95% CIs. The endpoints included access time, fluoroscopy time, successful dilation rate, stone-free rate, postoperative decrease in haemoglobin levels, transfusion rate, complication rate and length of postoperative hospital stay. RESULTS: A total of seven RCTs were included in the study, with clinical data reported for 697 patients. The overall access time was approximately 110 s shorter in the OSD group than in the serial dilation group (MD, -110.14; 95% CI -161.99 to -58.30; p<0.0001). The fluoroscopy time was shorter with OSD in all RCTs. In addition, the decrease in postoperative haemoglobin levels was approximately 2.3g/L less in patients in the OSD group than in those in the serial dilation group (MD, -0.23; 95% CI-0.39 to -0.07; p=0.004). No relationship was found between the successful dilation rate, stone-free rate, transfusion rate, or complication rate and the method of tract dilation. CONCLUSION: OSD is a safe and efficacious tract dilation technique that can reduce the access time, fluoroscopy time and postoperative decrease in haemoglobin level. No difference was found in the successful dilation rate, stone-free rate, transfusion rate or rate of complications between the OSD and serial dilation groups. The difference in the length of postoperative hospital stay was uncertain. OSD may be a better method of tract creation for PCNL.

A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer.

AIM: To explore the molecular mechanism of nonmuscle invasive bladder cancer (NMIBC), matched normal, and cancer tissues of 10 NMIBC were examined for RNA sequencing. METHODS: We profiled the messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression of patients with NMIBC. Differentially expressed mRNAs and lncRNAs were screened between cancer and normal tissues and validated by quantitative polymerase chain reaction (qPCR), and lncRNA-mRNA-miRNA interaction network was constructed. RESULTS: A total of 91 upregulated and 190 downregulated genes and 34 upregulated and 58 downregulated lncRNAs were screened from the sequencing result. The differentially expressed mRNAs were enriched in focal adhesion, rap1 signaling pathway, Hippo signaling pathway, PI3K-Akt signaling pathway, extracellular matrix (ECM)-receptor interaction, Ras signaling pathway, and mitogen-activated protein kinases signaling pathway, of which some pathways were involved in the cancer development. In the RNA sequencing, KIT and laminin subunitγ γ3 (LAMC3) were significantly downregulated in the NMIBC group compared with the normal group. The results of quantitative reverse transcription PCR showed that the expression of LAMC3 and KIT were significantly decreased in the NMIBC group compared with the normal group. The lncRNA-mRNA-miRNA interaction network was constructed by Cytoscape software to further investigate the interaction correlations. The results implied that KIT and LAMC3 might regulate the lncRNAs (such as ENST00000445707, ENST00000501122, ENST00000505254, ENST00000528986, ENST00000557661, ENST00000602964, ENST00000614517, ENST00000620864, and ENST00000623414) by the miRNAs (such as hsa-let-7f-2-3p, hsa-miR-125a-3p, hsa-miR-134-3p, hsa-miR-191-5p, hsa-miR-210-5p, hsa-miR-30a-5p, hsa-miR-30d-5p, hsa-miR-30e-5p, hsa-miR-92a-2-5p, and hsa-miR-95-3p), and finally played a role in the development of NMIBC cancer. CONCLUSION: Altogether, our study preliminarily indicated that KIT and LAMC3 might play a crucial role in the development of NMIBC cancer via a complex mRNA-lncRNA-miRNA regulatory network.