Guanghui Hu

Coffee consumption and prostate cancer risk: a meta-analysis of cohort studies.

This meta-analysis was conducted to assess the association between coffee consumption and prostate cancer risk. Thirteen cohort studies with 34,105 cases and 539,577 participants were included in the meta-analysis. The summary relative risks (RRs) with 95% confidence intervals (CIs) for different coffee intake levels were calculated. Dose-response relationship was assessed using generalized least square trend estimation. The pooled RR for the highest vs. lowest coffee intake was 0.90 (95% CI: 0.85–0.95), with no significant heterogeneity across studies (P = 0.267; I2= 17.5%). The dose-response analysis showed a lower cancer risk decreased by 2.5% (RR = 0.975; 95% CI: 0.957–0.995) for every 2 cups/day increment in coffee consumption. Stratifying by geographic region, there was a statistically significant protective influence of coffee on prostate cancer risk among European populations. In subgroup analysis of prostate cancer grade, the summary RRs were 0.89 (95% CI: 0.83–0.96) for nonadvanced, 0.82 (95% CI: 0.61–1.10) for advanced and 0.76 (95% CI: 0.55–1.06) for fatal diseases. Our findings suggest that coffee consumption may be associated with a reduced risk of prostate cancer and it also has an inverse association with nonadvanced prostate cancer. Because of the limited number of studies, more prospective studies with large sample size are needed to confirm this association.

Fruit and vegetable consumption and risk of bladder cancer: an updated meta-analysis of observational studies

This meta-analysis was conducted to assess the association between fruit and vegetable intake and bladder cancer risk. Eligible studies published up to August 2014 were retrieved both through a computer search of PubMed, Embase and the Cochrane library and through a manual review of references. The summary relative risks with 95% confidence intervals (CIs) for the highest versus the lowest intakes of fruits and vegetables were calculated with random-effects models. Heterogeneity and publication bias were also evaluated. Potential sources of heterogeneity were detected with metaregression. Subgroup analyses and sensitivity analyses were also performed. A total of 27 studies (12 cohort and 15 case–control studies) were included in this meta-analysis. The summary relative risks for the highest versus lowest were 0.84 (95% CI: 0.72–0.96) for vegetable intake and 0.81 (95% CI: 0.73–0.89) for fruit intake. The dose–response analysis showed that the risk of bladder cancer decreased by 8% (relative risk=0.92; 95% CI: 0.87–0.97) and 9% (relative risk=0.91; 95% CI: 0.83–0.99) for every 200 g/day increment in vegetable and fruit consumption, respectively. Sensitivity analysis confirmed the stability of the results. Our findings suggest that intake of vegetables and fruits may significantly reduce the risk of bladder cancer. Further well-designed prospective studies are warranted to confirm these findings.

LncRNA-SARCC suppresses renal cell carcinoma (RCC) progression via altering the androgen receptor(AR)/miRNA-143-3p signals

While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK. In addition, bisulfite sequencing analysis substantiated that LncRNA-SARCC promoter was highly methylated in renal cancer tissues compared with paired non-cancerous renal tissues. Notably, treating with Sunitinib, the multi-targeted receptor tyrosine kinase inhibitor, increased the expression of LncRNA-SARCC, which decreased RCC cells resistance to Sunitinib. Thus, our study presented a road map for targeting this newly identified LncRNA-SARCC and its pathway, which expands potential therapeutic strategies for RCC treatment.

Transcutaneous electrical nerve stimulation in the treatment of patients with poststroke urinary incontinence

Purpose To investigate the therapeutic effect of transcutaneous electrical nerve stimulation (TENS) on poststroke urinary incontinence (UI). Patients and methods Sixty-one patients with poststroke UI were enrolled at the Neurology Department in the Shanghai Tenth People’s Hospital of Tongji University between January 2010–January 2011 and were divided into treatment and control groups (n=32 and n=29, respectively). TENS was applied to the treatment group, while the control group received basic therapy. The therapeutic group completed the whole set of TENS therapy with a treatment frequency of 30 minutes once a day for 60 days. The positive electrode was placed on the second lumbar spinous process, and the negative electrodes were inside the middle and lower third of the junction between the posterior superior iliac spine and ischia node. The overactive bladder symptom score, Barthel Index, and urodynamics examination were estimated before and after therapy in both groups. Results The daily micturition, nocturia, urgent urination, and urge UI in the treatment group significantly improved compared to the control group (P<0.05). The patients in the treatment group were superior in the self-care ability of daily living and also had an advantage over the indexes on maximum cystometry volume, flow rate, and the pressure of detrusor in the end of the filling phase. Conclusion TENS improved incontinence symptoms, enhanced the quality of life, and decreased adverse effects; hence, it is recommended in treating poststroke UI.

miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3β in human renal cell carcinoma

MicroRNAs play a crucial role in cancer progression and metastasis. miR-203a has been identified as a tumor suppressor in various cancers. However, its functions in renal cell carcinoma have not been illustrated. In this study, we detected the miR-203a expression in renal cell carcinoma and evaluated its association with clinical features. Overexpression of miR-203a was found in renal cell carcinoma tissues and renal cell carcinoma cells. High miR-203a expression is correlated with tumor stage and short overall survival time. Bioinformatics and luciferase assay confirmed that glycogen synthase kinase-3β was a target gene of miR-203a. Silencing of miR-203a could inhibit cell proliferation and migration, arrest them in G1 phase, and promote apoptosis in vitro. miR-203a promotes the progression of renal cell carcinoma and predicts a poor prognosis.

The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

A novel minimally invasive percutaneous nephrolithotomy technique: safety and efficacy report

Abstract Objective. The aim of this study was to evaluate the outcome and determine the complications of ultrasound-guided 16 F tract percutaneous nephrolithotomy (PCNL) by review of over 1000 cases in a Chinese hospital. Material and methods. A total of 1368 patients underwent 16 F tract PCNL in the hospital between March 2007 and July 2013. Surgery was performed under general anesthesia in all cases. Central venous puncture was chosen as a puncture device. Complications, residual stones, stone clearance and the need for auxiliary treatments were evaluated. Management experience was evaluated with respect to the complications. Results. Complications occurred in 275 out of 1368 patients (20.1%). There were 102 Clavien grade 1 (7.4%), 121 grade 2 (8.8%) and 48 grade 3 (3.5%) complications, but no grade 4 or 5 complications. Access to the kidney was established in 99.7% of cases and 82.0% of cases had complete stone clearance without undergoing further PCNL. Auxiliary treatments included shockwave lithotripsy in 135 patients, second-phase PCNL in 49 patients and ureteroscopy in 63 patients. Three cases of rare complications occurred, including a double-J stent translocated to the chest, and intraoperative acute pulmonary edema and heart failure. Severe intraoperative or postoperative complications should be managed immediately. Conclusion. An ultrasound-guided mini-tract PCNL is safe and convenient, even for patients with complicated stones.

High expression of the secreted protein dickkopf homolog 4: Roles in invasion and metastasis of renal cell carcinoma and its association with Von Hippel-Lindau gene

The aim of this study was to investigate the effects of the dickkopf homolog 4 (DKK4)/Wnt/β-catenin signaling pathway on tumorigenesis and metastasis in clear cell renal cell carcinoma (ccRCC), as well as to elucidate the underlying mechanisms. We examined the expression of DKK4 in 30 cases of ccRCC and matched adjacent normal tissues, and investigated its correlation with clinicopathological characteristics. Stable DKK4-transfected cells were established, and DKK4 functional analyses were performed, including a T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter assay, and experiments on cell viability, apoptosis, invasive capability and tumor growth in vivo. Finally, western blot analysis was performed to detect Von Hippel-Lindau (VHL) expression in 50 clinical specimens. The expression levels of the DKK4, β-catenin and β-catenin downstream target genes, cyclin D1 and c-myc, were determined in the these specimens, as well as in RCC4(-), T3-14(+) cell lines by qRT-PCR and western blot analysis. The same tests were also performed in human embryonic kidney (HEK)293 cells which were transfected with the pCDH-DKK4 plasmid. After 6 weeks the tumor weight significantly increased in the mice transfected with the tumor cells. DKK4 mRNA and protein expression levels were significantly upregulated (p<0.001). DKK4 was distinctly overexpressed (68.0%) in all patient tissues. VHL(-) samples accounted for 60.0% of all samples, while DKK4 expression was significantly upregulated in 50% of these samples, indicating a correlation with VHL(-) expression (r=0.403, p<0.05). We also observed reduced expression levels of cyclin D1, c-myc and β-catenin (to a greater extent) in the VHL(-), RCC4(-) and T3-14(+) cells, as well as in the stably transfected HEK293 cells. DKK4 may be an oncogene, and its upregulated expression may be involved in the pathogenesis of ccRCC as a downstream gene of VHL. By activating other pathways apart from the Wnt/β-catenin pathway, DKK4 may play an important role in ccRCC tumorigenesis and metastasis.

Roscovitine protects murine Leydig cells from lipopolysaccharide-induced inflammation

Roscovitine is a cyclin-dependent kinase inhibitor, which has been previously investigated for its anticancer effects. It has also been confirmed that roscovitine can downregulate the expression of myeloid cell leukemia-1 protein to inhibit inflammation. In the present study, roscovitine was used to treat inflammation in lipopolysaccharide (LPS)-induced model mice. At the cellular level, Leydig cells isolated from mouse testis were assessed for inflammatory factors. It was revealed that roscovitine successfully reduced inflammation-associated injury induced by LPS pretreatment. At the molecular level, roscovitine was found to exert this effect through promotion of adenosine monophosphate-activated protein kinase phosphorylation. To the best of our knowledge, the present study was the first to suggest that roscovitine has a protective role in Leydig cells through its anti-inflammatory action.

Aldosterone Blocks Rat Stem Leydig Cell Development In Vitro

Aldosterone (ALDO) is a primary endogenous mineralocorticoid, appearing as the main hormone controlling sodium and water homeostasis. Its emerging role in the development of many organs has gained interest over the past few years. In the testis, Leydig cells contain mineralocorticoid receptors and ALDO stimulates androgen synthesis via the mineralocorticoid receptors in rat adult Leydig cells. Although ALDO pharmacologically promoted the Leydig cell function, its role in Leydig cell development was unclear. In the present study, we investigated effects of ALDO on rat stem Leydig cell (SLC) proliferation and differentiation. Using an in vitro culture system of the seminiferous tubules from Leydig cell-depleted testis and EdU (a modified thymidine analog) incorporation into the SLC for flurorescent labeling to judge its DNA synthesis and measurement of medium testosterone production, steroidogenesis-related gene and protein expression, we found that: (1) ALDO suppressed EdU incorporation into SLCs at 100 nM via mineralocorticoid receptor-mediated mechanism and (2) ALDO reduced Leydig cell number. In conclusion, ALDO pharmacologically blocked rat SLC development.