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Background: The discovery of cuproptosis provides a new way to make full use of the pathophysiological effects of copper for anticancer therapy and could help identify a therapeutic target in bladder cancer. Methods: In this study, 411 BLCA tumor samples from the Cancer Genome Atlas (TCGA) cohort were obtained. Differentially expressed genes (DEGs) between chemotherapy-sensitive and chemotherapy-resistant mouse bladder cancers were also obtained. Sixteen genes were defined as cuproptosis-related genes (CRGs), and the cutoff score was calculated based on LASSO Cox regression. CCK-8 and Transwell assays were used to detect the migration and proliferation of 5637 and T24 cells, respectively. Liarozole dihydrochloride (L-D), a mild P450, inhibits the expression of CYP26B1. Multiple immunohistochemistry analyses were used to explore the association between the immune microenvironment and CRGs.Results: A higher Cuproptosis score was significantly associated with worse overall survival in BLCA (pCYP26B1andCYP26B1may be negatively associated with DNA damage and repair. In vitro experiments indicated that overexpression of CYP26B1 enhanced the migration and proliferation of BLCA cells, while L-D inhibited the migration and proliferation of BLCA cells. A higher expression level of Dihydrolipoamide S-Succinyltransferase (DLST) serves could as a risk factor in patients treated with atezolizumab and higher expression ofDLSTsuggest an immunosuppressive microenvironment. Conclusions:CYP26B1may be a therapeutic target for bladder cancer, and the higher expression of DLST may suggest an immunosuppressive microenvironment in BLCA.

The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis.RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis.P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04).The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.

Background. Clear cell renal cell carcinoma’s (ccRCC) occurrence and development are strongly linked to the metabolic reprogramming of tumors, and thus far, neither its prognosis nor treatment has achieved satisfying clinical outcomes. Methods. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively, provided us with information on the RNA expression of ccRCC patients and their clinical data. Cuproptosis-related genes (CRGS) were discovered in recent massive research. With the help of log-rank testing and univariate Cox analysis, the prognostic significance of CRGS was examined. Different cuproptosis subtypes were identified using consensus clustering analysis, and GSVA was used to further investigate the likely signaling pathways between various subtypes. Univariate Cox, least absolute shrinkage and selection operator (Lasso), random forest (RF), and multivariate stepwise Cox regression analysis were used to build prognostic models. After that, the models were verified by means of the C index, Kaplan–Meier (K-M) survival curves, and time-dependent receiver operating characteristic (ROC) curves. The association between prognostic models and the tumor immune microenvironment as well as the relationship between prognostic models and immunotherapy were next examined using ssGSEA and TIDE analysis. Four online prediction websites-Mircode, MiRDB, MiRTarBase, and TargetScan-were used to build a lncRNA-miRNA-mRNA ceRNA network. Results. By consensus clustering, two subgroups of cuproptosis were identified that represented distinct prognostic and immunological microenvironments. Conclusion. A prognostic risk model with 13 CR-lncRNAs was developed. The immune microenvironment and responsiveness to immunotherapy are substantially connected with the model, which may reliably predict the prognosis of patients with ccRCC.

This work aimed to investigate the molecular mechanism of the activation of hypoxia-inducible factors under different low oxygen partial pressures.Strictly follow in vitro aseptic culture of bladder cancer cell line UMUC3 and when the cells grow in the logarithmic phase, culture the cells under different low oxygen partial pressures. Among these groups, two groups of cells were transfected with small interfering-hypoxia inducible factor 1α (si-HIF-1α) liposome plasmids to silencing the HIF-1α expression.Cell cloning experiment showed that HIF-1α will increase cell adhesion and proliferation under hypoxia. Matrigel angiogenesis experiment showed that hypoxia has a negative impact on the angiogenesis of tumor cells. Cell scratch test indicated that hypoxia has a greater impact on the migration ability of cancer cells, and HIF-1α has a significant impact on the migration process. Cell invasion test proved that hypoxia has a greater impact on the invasion ability of cancer cells, and HIF-1α has a great impact on the invasion process.HIF-1α can target the regulatory gene vascular endothelial growth factor to promote tumor cell proliferation, migration, invasion, neovascularization and lymph node metastasis.Por lo tanto, este trabajo investiga el mecanismo molecular de la activación de factores inducibles por hipoxia bajo diferentes presiones parciales de oxígeno bajas.Siga estrictamente el cultivo aséptico in vitro de la línea celular de cáncer de vejiga UMUC3 y cuando las células crezcan en la fase logarítmica, cultive las células bajo diferentes presiones parciales de oxígeno bajas. Entre estos grupos, se transfectaron dos grupos de células con plásmidos de liposomas si-HIF-1α para silenciar la expresión de HIF-1α.El experimento de clonación celular mostró que HIF-1α aumentará la adhesión y proliferación celular bajo hipoxia. El experimento de angiogénesis de Matrigel mostró que la hipoxia tiene un impacto negativo en la angiogénesis de las células tumorales. La prueba de raspado celular indicó que la hipoxia tiene un mayor impacto en la capacidad de migración de las células cancerosas, y HIF-1α tiene un impacto significativo en el proceso de migración. La prueba de invasión celular demostró que la hipoxia tiene un mayor impacto en la capacidad de invasión de las células cancerosas y HIF-1α tiene un gran impacto en el proceso de invasión.HIF-1α puede dirigirse al gen regulador vascular endothelial growth factor para promover la proliferación, migración, invasión, neovascularización y metástasis en los ganglios linfáticos de las células tumorales.

BACKGROUND Cordyceps cicadae is beneficial in treating renal diseases, especially in inhibiting renal ischemia/reperfusion injury (IRI). The aim of this study was to systematically analyze and predict the potential mechanism of Cordyceps cicadae in renal IRI therapy using network pharmacology. MATERIAL AND METHODS Cordycepin, adenosine, and cordycepic acid are the 3 major medicinal ingredients in Cordyceps cicadae. Based on network pharmacology, the 3D structure of the 3 compounds were obtained, and then the common targets between these compounds and renal IRI were analyzed and determined. We used the ingredient-target (I-T), protein-protein interaction (PPI) networks, the enrichment analysis of Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to find the possible pharmacological mechanism of Cordyceps cicadae in treating renal IRI. RESULTS Through target fishing and analysis, the 3 active ingredients of Cordyceps cicadae shared 81 target genes with renal IRI. I-T network showed that adenosine had the highest degree, and 5 genes were associated with the 3 active ingredients. PPI network analysis showed that ALB, GAPDH, CASP3, MAPK1, FN1, and IL-10 play a pivotal role. The enrichment analysis of GO and KEGG showed that Cordyceps cicadae can treat renal IRI through MAPK, cAMP, PPAR, Rap1, and HIF-1 signaling pathways. CONCLUSIONS Cordyceps cicadae exerts its therapeutic effect on renal IRI via multiple targets and pathways. Nevertheless, further experimentation is needed to verify this. The method of network pharmacology provides an effective method of determining the comprehensive action mechanism of Traditional Chinese Medicine (TCM).

BACKGROUND Deep convolutional neural networks have been applied to predict bladder cancer recurrence by analysing CT scans. However, such models suffer from a limited number of images collected from hospitals, leading to unstable performance. The size of medical datasets is limited by the complexity and high cost of large-scale studies, making it difficult to obtain rich training data in medical research. OBJECTIVE In this study, we aim to investigate 13 mainstream deep convolutional neural networks and build a pipeline of bladder cancer recurrence risk classification using CT scans and pre-trained deep learning convolutional neural networks. METHODS A five-year follow-up dataset from 101 patients with bladder cancer was collected from the Department of Urology at Xuzhou Central Hospital, Jiangsu Province, China. The CT scans of each patient were extracted from the dataset and formed an image set of 492 scans. 5-fold cross-validation were used to assess the performance and general error estimation of deep learning models. 13 mainstream deep convolutional neural networks were built to predict bladder cancer's recurrence risk level. Model performance was assessed by accuracy, precision, recall, F1-score and Area Under the Curve (AUC). RESULTS The pre-trained VGG16 had the best accuracy of 0.954 compared to the other 12 pre-trained models. The model also had a precision of 0.945, recall of 0.946, and F1-score of 0.943. The AUC for short-term recurrence was 0.978, for medium-term recurrence was 0.981, and for long-term recurrence was 0.975. CONCLUSIONS Transfer learning provided a new way to deal with bladder cancer recurrence risk classification with deep learning and small-scale dataset. A pre-trained VGG16 performed the best in predicting the risk of bladder cancer recurrence using CT scans.

Introduction Transurethral seminal vesiculoscopy (TSV) is a common treatment for obstructive azoospermia but has a high rate of recurrence. Aim Introduce a new method involving indwelling double-J (D-J) tubes in seminal vesicles during TSV in order to reduce recurrent rate and refractory obstructive azoospermia. Methods A prospective study was performed to compare the effects and complications of patients treated with or without indwelling D-J tubes after TSV. General information and TSV Surgical parameters, including age, body mass index, preoperational antibiotics, history of urinary tract disease, surgical time length (STL) and complications during and after the surgery, were collected and used as baseline information. The current study compared the postoperative complications and postoperative hospital days (PHD), as well as the recurrence rate of haemospermia between the two groups. Results A total of 59 cases, including 28 patients who underwent treatment with indwelling D-J tubes and 31 patients who underwent treatment with the standard TSV procedure, were enrolled in this study. There was no statistically significant difference in baseline data, Intraoperative and postoperative complications and postoperative hospital days between the two groups (p > 0.05), and there was a statistically significant difference in STL and recurrence rate between the two groups (p

Objective To introduce a new sequential sheath urethral dilatation (SSUD) method to treat male short segment posterior urethral stricture (MSS-PUS). Methods 67 male patients who had a MSS-PUS were enrolled and randomly assigned to one of two groups: group A (SSUD) and group B (Cold knife internal urethrotomy, CIU). Baseline information, including age, diabetes status, location of urethral stricture, preoperative ultrasound post-void residual (PVR) measurement, preoperative maximum urinary flow rate (Qmax), and preoperative International Prostate Symptom Score (IPSS) were collected and compared between groups. The operation time, postoperative length of hospital stay, indwelling catheter size, success rate, operative complications, recurrence, postoperative PVR, Qmax, and IPSS were evaluated and compared between the two groups. Results There was no significant difference in the baseline data, postoperative data, the complication, recurrence rates, postoperative length of hospital stay and postoperative PVR measurements between the two groups (p > 0.05), but the difference in immediate success rate, operative time, indwelling catheter size, postoperative Qmax and postoperative IPSS was statistically significant (p

Jiangang Chen,1,2 Lin Hao,1,3 Shaoqi Zhang,1 Yong Zhang,2 Bingzheng Dong,1,3 Qianjin Zhang,1 Conghui Han1,3 1Medical College of Soochow University, Suzhou, Jiangsu Province, 215123, People’s Republic of China; 2Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China; 3Department of Urology, Xuzhou Central Hospital, Xuzhou Clinical College Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu Province, 221009, People’s Republic of ChinaCorrespondence: Conghui HanDepartment of Urology, Xuzhou Central Hospital, Xuzhou Clinical College Affiliated to Xuzhou Medical University, 199 Jiefang South Road, Xuzhou, Jiangsu, 221009, People’s Republic of ChinaEmail conghuihandoctor@163.comBackground: We conducted a two-center study to investigate the prognostic value of preoperative fibrinogen–albumin ratio (FAR) in patients undergoing radical cystectomy (RC).Methods: The clinical and survival data of 267 patients with bladder cancer (BCa) treated with RC were collected, of which 140 patients from Xuzhou Central Hospital were divided into training set and 127 patients from The Second Affiliated Hospital of Nantong University were divided into validation set. X-tile software was used to obtain the optimal cut-off values for preoperative platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and FAR. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of PLR, NLR, FAR and modified Glasgow prognostic score (mGPS). Kaplan–Meier curves were used to assess overall survival (OS) and progression-free survival (PFS) of patients in different FAR groups. Univariate and multivariate Cox regression were used to assess patients’ independent risk factors, and R software was used to construct prognostic nomograms.Results: In the training set, the optimal cut-off values for PLR, NLR and FAR were 76.76, 3.97 and 0.08, respectively. Both in the training and validation sets, FAR had better ability to predict OS and PFS than PLR and NLR, and patients in the higher FAR group had worse OS and PFS. In the multivariate Cox regression analysis, FAR was an independent risk factor for OS [hazard ratio (HR) 3.569, 95% confidence interval (CI): 1.015– 12.546, P=0.047] and PFS [HR 5.071, 95% CI: 1.394– 18.451, P=0.014]. In addition, FAR-based prognostic nomograms had high predictive ability than TNM staging.Conclusion: Preoperative FAR is an independent prognostic factor for OS and PFS in BCa patients treated with RC, and a high FAR predicted a poor prognosis. In addition, a prognostic nomogram based on FAR can better predict individual survival.Keywords: fibrinogen–albumin ratio, bladder cancer, radical cystectomy, overall survival, progression-free survival

Genetic, lifestyle, and environmental factors contribute to the etiology of polycystic ovary syndrome (PCOS). Increased body mass index (BMI) exacerbates the reproductive and metabolic parameters and reduces the fecundity of women with PCOS. This is a secondary analysis of a large-sample, multicenter, randomized controlled trial conducted at 21 sites in Chinese mainland. A total of 1000 women diagnosed with PCOS were enrolled in this trial. Of these, 998 women with PCOS were included in the analysis. Increased BMI was associated with more severe menstrual irregularities, elevated testosterone level, higher prevalence of metabolic syndrome, and poorer quality of life. The rates of ovulation per woman for the normal, overweight, and obese BMI groups were 83.0%, 78.2%, and 63.6%, respectively (P

Background Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. Methods Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I–T) and protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. Results Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. Conclusions S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

During spaceflight, astronauts are subjected to various physical stressors including microgravity, which could cause immune dysfunction and thus potentially predispose astronauts to infections and illness. However, the mechanisms by which microgravity affects innate immunity remain largely unclear. In this study, we conducted RNA-sequencing analysis to show that simulated microgravity (SMG) suppresses the production of inflammatory cytokines including tumor necrosis factor (TNF) and interleukin-6 (IL-6) as well as the activation of the innate immune signaling pathways including the p38 mitogen-activated protein kinase (MAPK) and the Erk1/2 MAPK pathways in the Enteropathogenic escherichia coli (EPEC)-infected macrophage cells. We then adopted hindlimb-unloading (HU) mice, a model mimicking the microgravity of a spaceflight environment, to demonstrate that microgravity suppresses proinflammatory cytokine-mediated intestinal immunity to Citrobacter rodentium infection and induces the disturbance of gut microbiota, both of which phenotypes could be largely corrected by the introduction of VSL#3, a high-concentration probiotic preparation of eight live freeze-dried bacterial species. Taken together, our study provides new insights into microgravity-mediated innate immune suppression and intestinal microbiota disturbance, and suggests that probiotic VSL#3 has great potential as a dietary supplement in protecting individuals from spaceflight mission-associated infections and gut microbiota dysbiosis.

Background. Castration-resistant prostate cancer (CRPC), one of the prostate cancers, is a medical conundrum around the world. Some studies have demonstrated that many long noncoding RNAs in exosomes are very important in many types of cancer, including prostate cancer. However, until now, the function of exosomes in the occurrence and development of CRPC has not been reported. Methods. In vitro, cell coculture was used in LNCap cells and PC-3 cells, while the isolation and purification of exosomes and the subsequent treatment assays were used in functional studies. In vitro assays were performed to detect the transformation of ADPC cells (androgen-dependent prostate cancer) into AIPC cells (androgen-independent prostate cancer). Subsequently, a lncRNA-sequencing assay was performed to detect different lncRNA expression profiles in ADPC cells cocultured with or without AIPC exosomes. The role of LINC01213 was analysed by a TCGA database after silencing the expression of LINC01213. CCK-8, qRT-PCR, and Western blotting studies were performed to analyse the possible mechanism by which exosomes participate in prostate cancer progression. Results. In the coculture system, ADPC cells acquired androgen deprivation tolerance through exosome-mediated intercellular communication. Exosomes secreted by AIPC cells can promote the transformation of ADPC cells into androgen-independent cells in vitro and in vivo. lncRNA sequencing showed that LINC01213 was upregulated in exosomes derived from AIPC cell lines. The rescue experiments were preformed, and the results revealed that most of the functions of LINC01213 were performed by Wnt/β-catenin. Conclusions. All the findings showed that exosomes play a key role in CRPC progression by upregulating LINC01213 and activating Wnt/β-catenin signalling.

Purpose. We aimed to investigate the changes of serum and cell exosome miR-205 levels in patients with prostate carcinoma and its clinical significance. Materials and Methods. Firstly, pronouncement of miR-205 in normal and prostate carcinoma tissues was analyzed by using UALCAN database. The relationship between miR-205 in tumor tissues and the pathological and clinical characteristics of patients with prostate carcinoma were analyzed. Consequently, 60 people with prostate carcinoma were collected to the Minhang Hospital from August 2016 to August 2021. Serum of patients in the two groups was collected, and RNA in serum exosomes was extracted, and qRT-PCR was used to analyze the expression of miR-205 mediated by serum exosomes. Meanwhile, the relationship among the clinical as well as pathological aspects and bodement of patients with prostate carcinoma and the pronouncement level of miR-205 mediated by exosome was compared. Next, assays like wound healing and CKK-8 were used to investigate the effects of miR-205 in exosomes extracted from prostate carcinoma on the augmentation and metastasis of prostate carcinoma. Results. The results showed that the pronouncement level of miR-205 in tissues with prostate carcinoma was significantly lower than that in normal prostate tissues. In addition, the pronouncement level of miR-205 in fluid exosome of people with prostate carcinoma and exosomes derived from the lines of prostate carcinoma was considerably less than that in serum exosomes of healthy patients and that of normal cell lines of prostate. The pronouncement level of miR-205 in fluid exosomes of people with prostate carcinoma was negatively associated with cancer phase, uncontrolled cell division in lymph nodes, distant metastasis, and PSA level at initial diagnosis. Analysis (multivariate and univariate) showed that miR-205 pronouncement was a sovereign threat cause for prognosis of prostate cancer patients. Additionally, the pronouncement and metastasis of prostate carcinoma can be restricted by the overexpression of miR-205. Conclusion. The pronouncement of miR-205 in liquid derived exosomes is correlated with the prediction of people with prostate carcinoma and may be a new marker for identification and cure of prostate carcinoma.

Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

The prolyl 3-hydroxylase family member 4 (P3H4) (alias SC65) is implicated in a variety of physiological and pathological processes. However, little is known about the role of P3H4 in tumors. This study aimed to investigate the role of P3H4 in bladder cancer (BC) and the regulatory mechanisms that influence its expression. P3H4 was highly expressed in BC tissues. Knockdown of P3H4 inhibited BC cell proliferation, cell cycle, migration and invasion in vitro, and inhibited BC growth in vivo. We also found that ETV4 bound directly to the promoter region of P3H4 and activated its transcription. Furthermore, overexpression of ETV4 rescued the inhibition of proliferation and invasion induced by PH4 silencing. ETV4 was significantly overexpressed in the BC tissues. In conclusion, P3H4 functioned an oncogene role in BC progression, and ETV4 bound directly to the P3H4 promoter region to regulate its transcription.

Bladder cancer (BCa) is a common malignancy in the urinary system. Ras-related protein Rab-27A (RAB27A) and Ras-related protein Rab-27B (RAB27B) have been verified to be closely related to the development of many tumors. Since the role of both RAB27A and RAB27B in BCa have not been reported, we intended to explore the function and mechanism of RAB27A and RAB27B in BCa development. Reverse transcription quantitative polymerase chain reaction revealed that RAB27A/B showed high expression in BCa tissues and cells. Cell counting kit-8, wound healing and Transwell assays as well as western blot analyses revealed that silencing RAB27A/B suppressed BCa cell proliferation, migration and invasion as well as the epithelial-mesenchymal transition (EMT) process. Based on bioinformatics analysis and our experiments, microRNA-186-5p (miR-186-5p) was found to be the upstream miRNA of RAB27A/B in BCa. MiR-186-5p expression was significantly downregulated in BCa cells and tissues. MiR-186-5p directly targeted the 3'-untranslated region (3'-UTR) of RAB27A/B and downregulated both mRNA and protein levels of RAB27A/B in BCa cells. MiR-186-5p overexpression suppressed BCa cell proliferation, migration and invasion as well as the EMT process in vitro and inhibited tumor growth in vivo. Overexpressing RAB27A/B rescued the inhibitory effect of miR-186-5p on malignant phenotypes of BCa cells. Furthermore, miR-186-5p inactivated the phosphatidylinositol 3-Kinase (PI3K)/mitogen-activated protein kinase (MAPK) signaling pathway by downregulating the expression of RAB27A/B, as shown in western blot analysis. Overall, miR-186-5p suppressed BCa cell proliferation, migration, invasion and EMT process and inhibited xenograft tumor growth by targeting RAB27A/B to inactivate the PI3K/MAPK signaling.

miR-219-5p has been reported to act as either a tumor suppressor or a tumor promoter in different cancers by targeting different genes. In the present study, we demonstrated that miR-219-5p negatively regulated the expression of TBXT, a known epithelial–mesenchymal transition (EMT) inducer, by directly binding to TBXT 3′-untranslated region. As a result of its inhibition on TBXT expression, miR-219-5p suppressed EMT and cell migration and invasion in breast cancer cells. The re-introduction of TBXT in miR-219-5p overexpressing cells decreased the inhibitory effects of miR-219 on EMT and cell migration and invasion. Moreover, miR-219-5p decreased breast cancer stem cell (CSC) marker genes expression and reduced the mammosphere forming capability of cells. Overall, our study highlighted that TBXT is a novel target of miR-219-5p. By suppressing TBXT, miR-219-5p plays an important role in EMT and cell migration and invasion of breast cancer cells.

Aim: The aim of the study is to investigate the effect of Cynomorium songaricum (CS) on the damage caused by cyclophosphamide (CP) in SD rats. Methods: Rats with CP-induced oligoasthenospermia were treated with different concentration of CS. Testicle weight, epididymal sperm count (ESC), sperm motility, and serum testosterone were analyzed, and expression levels of Thy1, Oct4, PLZF, C-kit, and GDNF were detected in testis tissues. Transmission electron microscopy (TEM) was performed to observe the effect of CS on the spermatogenic damage by CP. Results: Compared with the CP group, there were significant differences in testicle weight, ESC, and sperm motility (p0.05). The qPCR results revealed a significant difference in Thy1, Oct4, PLZF and GDNF expression between the CP group and CS group (p 0.05). The damage of CP was cured by CS observed under TEM. Conclusion: CS can increase sperm counts in the epididymis and improve sperm motility and has a therapeutic effect on the spermatogenic damage caused by CP in SD rats.

Introduction There have been problems with low qualification operator-related complications and failures of transurethral seminal vesiculoscopy (TSV) in China. Aim To study the guiding role of seminal tract anatomical study (STAS) in TSV. Material and methods We performed STAS to study the structure, morphology, duct trajectory, and anatomical relationships between the seminal vesicles and the adjacent tissue in pelvic specimens from 12 adult cadavers. Then the surgical effects and complications of 82 cases of TSV performed by 3 doctors were retrospectively studied to compare the difference between the two groups of before and after the anatomical study. Results The anatomical studies of the 12 adult cadaveric pelvis specimens identified the lengths and widths of the right- and left-side seminal vesicles and tracts. The TSV can treat lesions located in the distal seminal tract and vesicle, but proximal lesions cannot be reached, which is an anatomical limitation of this technique. There were significant differences in the surgical times and the surgical validity rates between the 2 groups. Conclusions Our anatomical study of the seminal tract and seminal vesicles is valuable for guiding TSV in clinical practice.

Background This study aimed to determine whether the enhancer of the rudimentary homolog (ERH) gene regulates cell migration and invasion in human bladder urothelial carcinoma (BUC) T24 cells and the underlying mechanism. Methods First, we knocked down ERH in BUC T24 and 5637 cells by shRNA and then used wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays to determine the migration and invasion ability after ERH was knocked down. Moreover, we used gene expression profiling chip analysis and further functional experiments to explore the possible mechanism through which ERH knockdown downregulated metastasis ability in T24 cells. Results Wound healing cell scratch migration assays, transwell cell migration assays, transwell cell invasion chamber experiments and nude mouse tail vein transfer assays all showed that the metastasis ability was significantly inhibited in human BUC T24 and 5637 cells with ERH knockdown. A gene expression profiling chip analysis in T24 cells showed that the MYC gene may be an important downstream target of the ERH gene, and the functional experiments showed that MYC is a functional target of ERH in BUC T24 cells. Conclusion ERH knockdown could inhibit the metastasis of BUC T24 cells in vitro and in vivo. This study further explored the mechanism of the ERH gene in the metastasis of the T24 human bladder cancer cell line and found that ERH may regulate MYC gene expression. The results of this research provide a basis for the clinical application of ERH as a potential target for BUC treatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5423-9) contains supplementary material, which is available to authorized users.

Muscle-invasive bladder carcinoma (MIBC) accounts for 25% of newly diagnosed bladder carcinomas (BCs) and presents a high risk of progression and metastasis. This study aimed to identify reliable biomarkers associated with muscle invasion and prognosis to identify potential therapeutic targets for MIBC. Four gene datasets were downloaded from the Gene Expression Omnibus, and the integrated differentially expressed genes (DEGs) were then subjected to gene ontology (GO) terms and pathway enrichment analyses. Correlation analysis between the expression of the top-ranking DEGs and pathological T stages was performed to identify the genes associated with early muscle invasion. The corresponding prognostic values were evaluated, and co-expressed genes mined in the cBioPortal database were loaded into ClueGo in Cytoscape for pathway enrichment analysis. Using data mining from the STRING and TCGA databases, protein-protein interaction and competitive endogenous RNA networks were constructed. In total, 645 integrated DEGs were identified and these were mainly enriched in 26 pathways, including cell cycle, bladder cancer, DNA replication, and PPAR signaling pathway. S100A7 expression was significantly increased from the T2 stage and showed significantly worse overall survival and disease-specific survival in patients with BC. In total, 144 genes co-expressed with S100A7 in BC were significantly enriched in the IL-17 pathway. S100A7 was predicted to directly interact with LYZ, which potentially shows competitive binding with hsa-mir-140 to affect the expression of six lncRNAs in MIBC. In conclusion, high S100A7 expression was predicted to be associated with early muscle invasion and poor survival in patients with BC.