A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones.

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR). Methods: Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran's Q test were used to assess the directional pleiotropy and heterogeneity. Results: cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis. Conclusions: The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway.

Renal cell carcinoma (RCC) is one of the most common urological malignancies occurring in adult human kidneys worldwide. Recent research on antitumor drugs has focused on plant extracts, a class of compounds that play critical roles in cancer treatment. The present study aimed to investigate the potential antitumor effect of ginkgolic acid (GA) in RCC. Transwell invasion assay, cell counting kit-8 assay and flow cytometry were used to measure cell migration, cell viability and apoptosis, respectively. A network pharmacology approach was applied to identify pathway information, combining molecular docking techniques to screen for key target information. In the present study, GA inhibited the viability and proliferation of RCC cells (786-O and A498), both in vitro and in vivo, via G1 arrest. GA also reduced RCC cell invasion and migration. In addition, the epidermal growth factor receptor (EGFR) was identified as a critical target protein of GA, which significantly inactivated EGFR signaling in RCC (P<0.05). Collectively, the present study provided evidence that GA exerts its anticancer function by directly targeting the EGFR signaling pathway, revealing the potential of GA therapy for RCC.

Aurora-A regulates autophagy through the Akt pathway in human prostate cancer.

BACKGROUND: Aurora A kinase is frequently overexpressed in a variety of tumor types, including the prostate. However, the function of Aurora A in autophagy in prostate cancer has not been investigated. Here, we aimed to study the functioning mechanism and autophagy associated signaling pathways of Aurora A in prostate cancer. METHODS: To investigate the biological function of Aurora A, down-regulation of Aurora A was performed followed by functional testing assays. Immunohistochemistry was used to detect the expression of Aurora A in human prostate cancer specimens. CCK8, Transwell, flow cytometric analysis and measurement of tumor formation in nude mice were performed to test the effects of Aurora A down-regulation in vivo and in vitro. Signaling pathway analysis was performed by using Western blot. Autophagy activity was measured by monitoring the expression levels of LC3-II. RESULTS: Aurora A overexpression was significantly higher in human prostate cancer specimens than in BPH. Furthermore, Aurora A knockdown inhibited the proliferation of prostate cancer cells by suppressing the Akt pathway, indicating that Akt is a novel Aurora A substrate in prostate cancer. Additionally, Aurora A down-regulation prompts autophagy in prostate cancer cells. Most importantly, Aurora A ablation almost fully abrogates tumorigenesis in nude mice, suggesting that Aurora A is a key oncogenic effector in prostate cancer. CONCLUSIONS: Taken together, our data suggest that Aurora-A plays an important role in the suppression of autophagy by inhibiting the phosphorylation of Akt, which in turn prevents autophagy-induced apoptosis in prostate cancer.

The influence of zinc hydroxystannate on reducing toxic gases (CO, NO(x) and HCN) generation and fire hazards of thermoplastic polyurethane composites.

A uniform zinc hydroxystannate (ZnHS) microcube was synthesized to reduce toxicity and fire hazards of thermoplastic polyurethane (TPU) composites using ammonium polyphosphate as a flame retardant agent. The structure, morphology and thermal properties of ZnHS were characterized by X-ray diffraction, transmission electron microscopy and thermogravimetric analysis, respectively. Smoke suppression properties and synergistic flame retardant effect of ZnHS on flame retardant TPU composites were intensively investigated by smoke density test, cone calorimeter test, and thermalgravimetric analysis. Thermogravimetric analysis/infrared spectrometry and tube furnace were employed to evaluate the toxic gases (CO, NOx and HCN) of TPU composites. The incorporation of ZnHS into TPU matrix effectively improved the fire safety and restrained the smoke density, which is attributed to that the char residue catalyzed by ZnHS enhanced barrier effect that reduced peak heat release rate, total heat release, smoke particles and organic volatiles during combustion. Furthermore, the ZnHS synergist demonstrated high efficiency in catalytic degradation of the toxic gases, which obviously decreased total volatiled product and toxic volatiles evolved, such as the CO, HCN and NOx, indicating suppressed toxicity of the TPU composites.

Idiopathic abdominal cocoon syndrome with unilateral abdominal cryptorchidism and greater omentum hypoplasia in a young case of small bowel obstruction.

Abdominal cocoon syndrome (ACS) is a rare cause of intestinal obstruction due to total or partial encapsulation of the small intestine by a fibrocollagenous membrane. Idiopathic ACS with abdominal cryptorchidism and greater omentum hypoplasia is even rarer clinically. We successfully treated a 26-year-old male case of small bowel obstruction with acute peritonitis. He was finally diagnosed with idiopathic ACS with unilateral abdominal cryptorchidism and greater omentum hypoplasia during exploratory laparotomy. He then underwent enterolysis, cryptorchidectomy, and appendectomy. He recovered gradually from the operations and early postoperative inflammatory ileus. There has been no recurrence of intestinal obstruction since the operation, and he is still in follow-up. We analyzed his clinical data and retrospectively reviewed the literature, and our findings may be helpful for the clinical diagnosis and treatment on ACS.

Increased expression of ESCO1 is correlated with poor patient survival and its role in human bladder cancer.

There is increasing evidence suggesting that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) was involved in tumorigenesis. However, its role in bladder cancer remains unclear. In this study, we aimed to study the clinical correlation and biological significance of ESCO1 in bladder cancer. Our results showed that ESCO1 was significantly over-expressed in bladder cancer tissues compared with that in adjacent normal tissues. And, increased ESCO1 expression was significantly associated with higher grade (P < 0.001), higher tumor stage (P = 0.014), and multifocality (P = 0.042). Kaplan-Meier analysis and Cox proportional hazards model were performed to determine the prognostic significance of ESCO1, and the results showed that ESCO1 is a useful prognostic marker for bladder cancer patients. Moreover, we found that ESCO1 knockdown inhibited the growth, migration, and invasion of bladder cancer cells. In conclusion, our findings indicated that ESCO1 may play an important role in human bladder cancer, and ESCO1 might serve as a novel target and prognosis factor for human bladder cancer.

PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways.

BACKGROUND: PACE4 is a proprotein convertase capable of processing numerous substrates involved in tumor growth, invasion, and metastasis. However, the precise role of PACE4 during prostate cancer cell apoptosis has not been reported. METHODS: In the present study, human prostate cancer cell lines DU145, LNCaP, and PC3 were transfected with PACE4 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. RESULTS: We revealed that PACE4 siRNA exhibited antitumor activity by inducing apoptosis, as determined by Cell Counting Kit-8 (CCK-8), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide (MTT) assay, cell cycle analysis, Hoechst staining, caspase-3/7 activity, and western blot analysis. In addition, PACE4 siRNA significantly increased the ratio of Bax/Bcl-2, which led to the release of cytochrome c. Moreover, PACE4 siRNA also induced endoplasmic reticulum stress by increasing the expression of GRP78, GRP94, p-PERK, and p-eIF2α. The ratio of Bax/Bcl-2 and GRP78 were also increased in PACE4 gene knockdown prostate cancer cells compared with the control cells. CONCLUSION: These data demonstrate that PACE4 siRNA may exert its antitumor activity through mitochondrial and endoplasmic reticulum stress signaling pathways, indicating it may be a novel therapeutic target for prostate cancer.

The role of tumor suppressor gene SOX11 in prostate cancer.

SOX genes play an important role in a number of developmental processes. The transcription factor SOX11 is one of the members of the SOX family emerging as important transcriptional regulators. The aim of this study was to investigate the role of SOX11 in prostate cancer (PCa) and its expression pattern and clinical significance. The gene expression of SOX11 in human PCa tissues compared with benign prostate hyperplasia (BPH) tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. SOX11 overexpression cell model was used to examine the role of SOX11 in cell growth and metastasis in vitro. The results showed that the positive rate of SOX11 staining was 16.67 % (10/60) in cases of prostatic carcinoma and 81.67 % (49/60) in cases of BPH, and the difference of SOX11 expression between PCa and BPH was statistically significant (P < 0.001). SOX11 mRNA level was lowly expressed in PCa cell lines compared to RWPE-1. SOX11 overexpression suppresses PCa cell migration and invasion. In conclusion, our findings demonstrate that SOX11 could suppress cell proliferation, migration, and invasion of PCa in vitro.

Application of two micron laser vaporesection combined with transurethral resection of the prostate in treatment of benign prostatic hyperplasia: analysis of 340 cases.

PURPOSE: To evaluate clinical efficacy and safety of two micron laser vaporesection combined with transurethral resection of the prostate (TURP) in treating benign prostatic hyperplasia (BPH). METHODS: In total, 340 BPH patients aged 62-86 years, were treated with two micron laser vaporesection plus TURP. Mean prostatic volume was measured as 38-182 ml. Operative time, intraoperative hemorrhage volume, time of postoperative bladder irrigation, time of indwelling urinary catheter and surgical complications were examined. International Prostate Symptom Score (IPSS), quality of life score (QOL), maximal urinary flow rate (Qmax) and post void residual urine volume (PVR) were analyzed. RESULTS: All cases underwent the surgery successfully. No transurethral resection syndrome was noted. Mean operative time was (72±15) min. Mean intra operative hemorrhage volume was (48.4±13.0) ml. Four patients were transfused with 2 U of suspended red blood cells. Time of postoperative bladder irrigation ranged from 0.5-2.5 d. Time of indwelling urinary catheter was 3-6 d. After removing urinary catheter, mild urinary irritation symptoms were noted in 19 cases. Ten patients developing urinary infection were recovered following anti-infection therapy. One with secondary urethral stenosis was healed after urethral dilatation for three times. Postoperative IPSS, QOL, Qmax and PVR were (6.0±2.0), (2.0±0.2), (18.5±1.6) ml/s and (11.0±4.0) ml, significantly improved compared with preoperative levels (all P<0.05). Fifty eight cases with normal sexual function retained sexual function postoperatively and had no retrograde ejaculation. CONCLUSIONS: Two micron laser vaporesection plus TURP is efficacious and safe in treating BPH with mild lower urinary tract symptoms and perioperative complications.

Left laparoscopic radical nephrectomy in the presence of a duplicated inferior vena cava with complicated anomalous tributaries by a transmesocolic approach.

Laparoscopic radical nephrectomy should be executed under the most fundamental principle of early ligature of the renal artery to prevent diffusion of cancerous cells. This is extremely true in the treatment of large renal tumors touching the main renal vasculature. Obviously, the concomitance of a duplicated inferior vena cava (IVC) with associated aberrant tributaries will significantly increase the surgical difficulty and the procedural risk of vascular injury. Herein we describe a transperitoneal left laparoscopic radical nephrectomy for a large hilar left renal tumor in the presence of a duplicated IVC with complicated anomalous tributaries by a transmesocolic approach.

Comparison of single-surgeon series of transperitoneal laparoendoscopic single-site surgery and standard laparoscopic adrenalectomy.

OBJECTIVE: To assess the feasibility, safety, and efficacy of transperitoneal laparoendoscopic single-site (LESS) adrenalectomy and determine whether it shows any objective advantage compared with standard laparoscopy. METHODS: From August 2009 to May 2011, 13 transperitoneal LESS adrenalectomies were performed through a 2-3-cm skin incision using the TriPort access system. This cohort was compared with a contemporary 1:2 matched-pair group of 26 patients undergoing standard laparoscopic adrenalectomy by the same urologist. The perioperative outcomes, including cosmetic satisfaction scores, were statistically analyzed. RESULTS: The 2 groups were comparable with respect to patient demographics, estimated blood loss, and postoperative hospitalization (P > .05). The LESS procedures had a longer mean operative time (148.5 vs 112.9 minutes, P = .032) but a significantly lower postoperative visual analog pain scale score (2.3 vs 3.7, P = .001), fewer patients requiring analgesics (30.8% vs 73.1%, P = .011), and an earlier resumption of oral intake (21.6 vs 26.0 hours, P = .002). The mean length of the scar in the LESS group was much smaller (2.3 vs 5.9 cm, P < .0001) with a statistically significant greater mean cosmetic satisfaction score (9.5 vs 9.1, P = .042). CONCLUSION: The perioperative outcomes of transperitoneal LESS adrenalectomy for small adrenal tumors were comparable to those with the standard laparoscopic approach. It also provides better postoperative pain control, faster recovery of bowel function, and better cosmetic satisfaction than standard laparoscopy, albeit with a longer operative time.

Left transperitoneal laparoscopic partial nephrectomy in the presence of a left-sided inferior vena cava.

OBJECTIVES: To report a case and the surgical techniques of transperitoneal laparoscopic partial nephrectomy (LPN) in a patient with a small left renal mass and an aberrant left-sided inferior vena cava (IVC). METHODS: An otherwise healthy 49-year-old man with a body mass index of 23.1 kg/m(2) was diagnosed with a 5 × 6-cm mass in the left kidney. A transperitoneal LPN was performed in the presence of a left-sided IVC. The procedure was completed using standard laparoscopic instruments. The left renal vein was identified, with the gonadal vein used as an anatomic landmark. Slightly rostral to the location where the renal vein emptied into the left-sided IVC, 2 renal arteries were dissected and clamped individually using laparoscopic bulldog clamps. A standard LPN was then completed. RESULTS: The duration of the surgery was 182 minutes, and there was an estimated blood loss of 100 mL. The warm ischemic time was 31 minutes. The postoperative recovery was uneventful, and the patient was discharged to his home on postoperative day 7. A pathologic examination revealed a renal oxyphilic adenoma, which is a benign lesion. At the follow-up visits that were 1 month and 3 months after surgery, the patient was determined to be clinically healthy. CONCLUSIONS: The anomaly of a left-sided IVC is not an impediment to performing a transperitoneal LPN; however, the correct identification of the anatomical landmarks and the use of meticulous intraoperative techniques are of paramount importance during this procedure.