The effect of physical therapy and mechanical stimulation on dysfunction of lower extremities after total pelvic exenteration in cervical carcinoma patient with rectovesicovaginal fistula induced by radiotherapy: a case report.

BACKGROUND: Total pelvic exenteration is the ultimate solution for rectovesicovaginal fistula caused by radiation therapy, yet total pelvic exenteration frequently causes intraoperative complications and postoperative complications. These complications are responsible for the dysfunction of lower extremities, impaired quality of life, and even the high long-term morbidity rate, thus multidisciplinary cooperation and early intervention for prevention of complications are necessary. Physical therapy was found to reduce the postoperative complications and promote rehabilitation, yet the effect on how physiotherapy prevents and treats complications after total pelvic exenteration and pelvic lymphadenectomy remains unclear. CASE PRESENTATION: A 50-year-old Chinese woman gradually developed perianal and pelvic floor pain and discomfort, right lower limb numbness, and involuntary vaginal discharge owing to recurrence and metastasis of cervical cancer more than half a year ago. Diagnosed as rectovesicovaginal fistula caused by radiation, she received total pelvic exenteration and subsequently developed severe lower limb edema, swelling pain, obturator nerve injury, and motor dysfunction. The patient was referred to a physiotherapist who performed rehabilitation evaluation and found edema in both lower extremities, right inguinal region pain (numeric pain rate scale 5/10), decreased temperature sensation and light touch in the medial thigh of the right lower limb, decreased right hip adductor muscle strength (manual muscle test 1/5) and right hip flexor muscle strength (manual muscle test 1/5), inability actively to adduct and flex the right hip with knee extension, low de Morton mobility Index score (0/100), and low Modified Barthel Index score (35/100). Routine physiotherapy was performed in 2 weeks, including therapeutic exercises, mechanical stimulation and electrical stimulation as well as manual therapy. The outcomes showed that physiotherapy significantly reduced lower limb pain and swelling, and improved hip range of motion, motor function, and activities of daily living, but still did not prevent thrombosis. CONCLUSION: Standardized physical therapy demonstrates the effect on postoperative complications after total pelvic exenteration and pelvic lymphadenectomy. This supports the necessity of multidisciplinary cooperation and early physiotherapy intervention. Further research is needed to determine the causes of thrombosis after standardized intervention, and more randomized controlled trials are needed to investigate the efficacy of physical therapy after total pelvic exenteration.

Poly-L-lactic acid/gelatin electrospun membrane-loaded bone marrow-derived mesenchymal stem cells attenuate erectile dysfunction caused by cavernous nerve injury.

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function.

Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization.

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe2 O3 nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe2 O3 providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe3+ . In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.

d-Galactose induces the senescence and phenotype switch of corpus cavernosum smooth muscle cells.

Studies regarding age-related erectile dysfunction (ED) based on naturally aging models are limited by their high costs, especially for the acquisition of primary cells from the corpus cavernosum. Herein, d-galactose ( d-gal) was employed to accelerate cell senescence, and the underlying mechanism was explored. As predominant functional cells involved in the erectile response, corpus cavernosum smooth muscle cells (CCSMCs) were isolated from 2-month-old rats. Following this, d-gal was introduced to induce cell senescence, which was verified via ß-galactosidase staining. The effects of d-gal on CCSMCs were evaluated by terminal deoxynucleoitidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence staining, flow cytometry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, RNA interference (RNAi) was carried out for rescue experiments. Subsequently, the influence of senescence on the corpus cavernosum was determined via scanning electron microscopy, qRT-PCR, immunohistochemistry, TUNEL, and Masson stainings. The results revealed that the accelerated senescence of CCSMCs was promoted by d-gal. Simultaneously, smooth muscle alpha-actin (alpha-SMA) expression was inhibited, while that of osteopontin (OPN) and Krüppel-like factor 4 (KLF4), as well as fibrotic and apoptotic levels, were elevated. After knocking down KLF4 expression in d-gal-induced CCSMCs by RNAi, the expression level of cellular alpha-SMA increased. Contrastingly, the OPN expression, apoptotic and fibrotic levels declined. In addition, cellular senescence acquired partial remission. Accordingly, in the aged corpus cavernosum, the fibrotic and apoptotic rates were increased, followed by downregulation in the expression of alpha-SMA and the concurrent upregulation in the expression of OPN and KLF4. Overall, our results signaled that d-gal-induced accelerated senescence of CCSMCs could trigger fibrosis, apoptosis and phenotypic switch to the synthetic state, potentially attributed to the upregulation of KLF4 expression, which may be a multipotential therapeutic target of age-related ED.

Loperamide induces protective autophagy and apoptosis through the ROS/JNK signaling pathway in bladder cancer.

Bladder cancer is one of the most common carcinomas in the human urinary system worldwide. Loperamide, known as an antidiarrheal drug, exerts anti-tumor activities against various cancers. However, the effect of loperamide on bladder cancer cells remains unclear. Our study aimed to investigate the effect of loperamide on bladder cancer and explore the underlying mechanisms. We found that loperamide suppressed the proliferation of 5637 and T24 cells in a dose-dependent manner. Loperamide treatment showed both pro-apoptotic and pro-autophagic effects on bladder cancer cells. Moreover, it was revealed that loperamide induced reactive oxygen species (ROS) accumulation, leading to the activation of c-Jun N-terminal kinase (JNK) signaling pathway. Notably, ROS scavenger N-acetyl-L-cysteine (NAC) and JNK inhibitor SP600125 effectively attenuated the induction of autophagy and apoptosis triggered by loperamide. Finally, blocking autophagy with CQ could significantly enhance the anti-cancer effect of loperamide both in vitro and in vivo. Overall, these findings demonstrated that loperamide induced autophagy and apoptosis through the ROS-mediated JNK pathway in bladder cancer cells. Our results suggest that the strategy of combining loperamide with autophagy inhibitor CQ may provide a therapeutic option for the treatment of bladder cancer.

Laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism: a retrospective study based on 154 patients.

BACKGROUND: The purpose of this study was to investigate the clinical effect of laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism. METHODS: A retrospective analysis of cryptorchidism patients who were admitted to our hospital from July 2018 to July 2021. The patients were divided into the laparoscopic assisted trans-scrotal surgery group (n = 76) and the traditional surgery group (n = 78) according to the surgical method. RESULTS: All patients were successfully operated. There was no significant difference in operation time between the laparoscopic assisted trans-scrotal group and the traditional group (P>0.05). Although there was no significant difference in the postoperative hospital stay between the two groups, the time of postoperative hospital stay of the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (P = 0.062). Additionally, there was no significant difference in discharge rate on the first day after surgery between the two groups, but the discharge rate on the first day after surgery was more than 90% in both groups. In terms of postoperative complications, there were no cases of testicular retraction, testicular atrophy, inguinal hernia, or hydrocele that occurred in both groups. There was no significant difference in the incidence of scrotal hematoma between the two groups(P>0.05). Although there was no significant difference in the incidence of poor wound healing between the two groups(P>0.05), the incidence in the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (2.6% vs. 6.4%). CONCLUSION: Laparoscopic assisted trans-scrotal surgery is as safe and effective method as traditional surgery for patients with inguinal cryptorchidism, and could also provide a good appearance.

Paeoniflorin suppresses kidney inflammation by regulating macrophage polarization via KLF4-mediated mitophagy.

BACKGROUND: Macrophages M1 polarization involved in the process of renal inflammatory injury, is a well-established hallmark of chronic kidney disease (CKD). Paeoniflorin (PF), a water-soluble monoterpene glycoside extracted from Paeonia lactiflora, revealed renal anti-inflammatory activities in our previous study. However, the potential molecular mechanism of PF on CKD remains unknown. PURPOSE: The present study aims to investigate the regulation of PF on macrophage polarization in CKD. METHODS: A CKD model was established by cationic bovine serum albumin and a murine macrophage cell line RAW264.7 induced with lipopolysaccharide (LPS) were used to clarify the underlying mechanisms of PF in CKD. RESULTS: Results showed that PF exhibited favorable protective effects on CKD model mice by promoting renal function, ameliorating renal pathological injury and podocyte damage. Furthermore, PF inhibited the infiltration of M1 macrophage marker CD68 and iNOS in kidney tissue, but increased the proportion of M2 macrophage marker CD206. In RAW264.7 cells stimulated with LPS, the levels of cytokines including IL-6, IL-1ß, TNF-α, MCP-1 were lessened under PF treatment, while the levels of Arg1, Fizz1, IL-10 and Ym-1 were augmented. These results indicated that PF promoted macrophage polarization from M1 to M2 in vivo and in vitro. More importantly, PF repaired the damaged mitochondria through increasing mitochondrial membrane potential and reducing ROS accumulation. The mitophagy-related proteins PINK1, Parkin, Bnip3, P62 and LC3 were up-regulated by PF, accompanied by the incremental expressions of Krüppel-like transcription factor 4 (KLF4). Moreover, the promotion of mitophagy and inhibition of M1 macrophage polarization owing to PF were reversed by mitophagy inhibitor Mdivi-1 or silencing KLF4. CONCLUSION: Overall, PF suppressed renal inflammation by promoting macrophage polarization from M1 to M2 and inducing mitophagy via regulating KLF4. It is expected to provide a new strategy for exploring the effects of PF in treating CKD.

Enhanced recovery management in pediatric pyeloplasty: outcomes in a single institution and tips for improvement.

OBJECTIVE: We report the application of enhanced recovery after surgery (ERAS) regimens to pediatric patients undergoing laparoscopic pyeloplasty (LP), aiming to guide the practice of ERAS in pediatric LP. METHODS: From October 2018, we prospectively implemented a twenty-point ERAS regimen, including a modified LP procedure, for pediatric UPJO patients in a single institution. Data from 2018 to 2021 were collected and analyzed retrospectively. The variables gathered included: demographics, preoperative details and recovery elements. Outcomes were postoperative length of stay (POS), readmission rate, operation time and blood loss. RESULTS: A total of 75 pediatric patients (0-14 years) were included. The mean POS was 2.4 ± 1.4 days, shorter than that in recent studies in China (3.3 ± 1.4 days, 6 (3-16) days). None were redo, and six restenosis (8%) were improved after treatment with ureteral balloon dilatation. The mean operation time was 257.9 ± 54.4 min, and blood loss was 11.8 ± 10.0 ml. In the univariable analysis and multivariable analysis, no external drainage, sacral anesthesia, and withdrawal of the catheter on day one were independently associated with a POS of ≤ 2 d (p < 0.05). CONCLUSION: The implementation of this ERAS protocol for pediatric LP has resulted in a shorter length of stay without a higher readmission rate. Surgery techniques, drainage management and analgesia are the key to further improvement. ERAS for pediatric pyeloplasty should be encouraged.

Gambogenic acid induces apoptosis and autophagy through ROS-mediated endoplasmic reticulum stress via JNK pathway in prostate cancer cells.

Prostate cancer (PCa) is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC) with limited therapies. Gambogenic acid (GNA), a flavonoids compound isolated from Gamboge, exhibits anti-tumor capacity in various cancers. Our results showed that GNA revealed not only antiproliferative and pro-apoptotic activities but also the induction of autophagy in PCa cells. In addition, autophagy inhibitor chloroquine enhanced the pro-apoptosis effect of GNA. Moreover, the activation of JNK pathway and the induction of apoptosis and autophagy triggered by GNA were attenuated by JNK inhibitor SP600125. We also found that GNA significantly promoted reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress. Meanwhile, suppressing ER stress with 4-phenylbutyric acid (4-PBA) markedly blocked the activation of JNK pathway induced by GNA. Further research indicated that ROS scavenger N-acetyl-L-cysteine (NAC) effectively abrogated ER stress and JNK pathway activation induced by GNA. Furthermore, NAC and 4-PBA significantly reversed GNA-triggered apoptosis and autophagy. Finally, GNA remarkably suppressed prostate tumor growth with low toxicity in vivo. In conclusion, the present study revealed that GNA induced apoptosis and autophagy through ROS-mediated ER stress via JNK signaling pathway in PCa cells. Thus, GNA might be a promising therapeutic drug against PCa.

MitoTEMPO protects against podocyte injury by inhibiting NLRP3 inflammasome via PINK1/Parkin pathway-mediated mitophagy.

Activation of inflammation is an important pathogenic factor contributing to the development of chronic kidney disease (CKD). Recent studies manifested the implication of impaired mitophagy mediated NLRP3 inflammasome activation in the progression of CKD. Mitochondria-targeted antioxidant mitoTEMPO showed antioxidant and anti-inflammatory properties in kidney disease. This study aims to investigate the protective mechanism of mitoTEMPO on podocyte injury related to mitophagy and NLRP3 inflammasome. Our results showed that mitoTEMPO obviously ameliorated renal function and podocyte injury in CKD model rats induced by cationic bovine serum albumin (C-BSA). More importantly, mitoTMEPO significantly inhibited NLRP3 inflammasome activation compared with CKD model rats (P < 0.01). In vitro, TNF-α damaged human podocyte cells (HPC) and activated NLRP3 inflammasome, which was rescued by NLRP3 inhibitor and mitoTEMPO. Meanwhile, mitoTEMPO lessened excessive mitochondrial ROS (mtROS) and degressive mitochondrial membrane potential (MMP) in HPC. We also found that mitoTEMPO induced mitophagy in vivo and in vitro. Moreover, silenced Parkin dramatically reserved the inhibitory effect of mitoTEMPO on NLRP3 inflammasome. Taking together, these findings reveal that mitoTEMPO ameliorated podocyte injury by inhibiting NLRP3 inflammasome via PINK1/Parkin pathway-mediated mitophagy. MitoTEMPO may be a new candidate to protect against podocyte injury in CKD.

Analysis of a Long Non-coding RNA associated Signature to Predict Survival in Patients with Bladder Cancer.

BACKGROUND: The study aimed to find a potential long non-coding RNA (lncRNA) model related to survival in bladder cancer by analyzing data in The Cancer Genome Atlas (TCGA). METHODS: We downloaded the gene expression data from the TCGA and analyzed the differentially expressed lncRNAs (DELs) between tumor and normal tissues. Patients were divided into training and testing groups, and a prognostic risk score model with lncRNAs was constructed by using data in the training group using multivariate Cox and lasso regression analysis. We divided patients into high-and low-risk groups according to the median value in the lncRNA signature model. Survival and receiver operating characteristic (ROC) curves were visualized in both groups. Further, we validated the model in the testing group. RESULTS: We screened 169 DELs for bladder cancer. The univariate Cox regression analysis showed that 13 lncRNAs were associated with prognosis with a p-value <0.01. We selected 12 of these lncRNAs to perform a multivariate Cox analysis to build the lncRNA signature. The formula with nine lncRNAs, namely, MIR497HG, LINC00968, NALCN-AS1, LINC02321, RNF144A-AS1, MNX1-AS1, FLJ22447, LINC01956, FLJ42969, was significantly related to prognosis. Patients in the high-risk group had a lower survival rate compared with the low-risk group in the training and testing sets (both p-values < 0.05) and the area of the ROC curve was 0.737 and 0.68, respectively. CONCLUSIONS: The study illustrated a significant lncRNA signature and indicated the risk score Cox model could be an important biomarker to predict the prognosis of bladder cancer.

Promoter Methylation-Mediated NPTX2 Silencing Promotes Tumor Growth in Human Prostate Cancer.

Neuronal pentraxin 2 (NPTX2), a secretory protein of neuronal pentraxins, was first identified in the nervous system. Several studies have shown that expression levels of NPTX2 are associated with the development of various cancers. However, whether NPTX2 is involved in prostate cancer progression is unclear. Herein, we found that NPTX2 is significantly reduced in prostate cancer tissues and cancer cell lines compared to control prostate tissues and control prostatic epithelial cell lines. Furthermore, the NPTX2 promoter is highly methylated in prostate cancer cells. Consistently, NPTX2 could be restored by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine, 5-AZA-dC). Overexpression of NPTX2 inhibited prostate cancer cell proliferation both in vitro and in vivo. In conclusion, our study demonstrated that NPTX2 acts as a tumor suppressor gene in prostate cancer.

Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489,and TMEM147-AS1,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.

Zhen-Wu-Tang Induced Mitophagy to Protect Mitochondrial Function in Chronic Glomerulonephritis via PI3K/AKT/mTOR and AMPK Pathways.

Chronic glomerulonephritis (CGN) is one of the major causes of end-stage kidney disease. Zhen-wu-tang (ZWT), as a famous Chinese herbal prescription, is widely used in China for CGN therapy in clinic. However, the mechanism of ZWT in CGN has not been fully understood. The present study explored the therapeutic effect and the underlying mechanism of ZWT on mitochondrial function in cationic bovine serum albumin (C-BSA)-induced CGN model rats and tumor necrosis factor (TNF-α)-damaged mouse podocytes. The renal functions were measured by serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological changes and ultrastructure of kidney tissues were evaluated by periodic acid-Schiff (PAS) staining and transmission electron microscopy. The levels of antioxidases, including mitochondrial catalase (CAT), superoxide dismutase 2 (SOD2), and peroxiredoxin 3 (PRDX3), in CGN rats were examined by real-time PCR. The mitochondrial functions of podocytes were measured by ATP concentration, mitochondrial membrane potential (MMP), and mitochondrial ROS (mtROS). For mitophagy level detection, the expressions of mitophagy-related proteins, including LC3, p62, heat shock protein 60 (HSP60), and translocase of outer mitochondrial membrane 20 (TOMM20), were measured by Western blot, as the colocation of LC3 and mitochondrial marker COX IV were evaluated by immunofluorescence. Our results manifested that ZWT ameliorated CGN model rats by a remarkable decrease in Scr and BUN, inhibition of mesangial matrix proliferation, protection against foot processes fusion, and basement membrane thickening. More importantly, ZWT protected against mitochondrial dysfunction by increasing the expressions of CAT, SOD2, and PRDX3 in CGN model rats, increased ATP content and MMP in podocytes, and decreased excessive mtROS. Furthermore, ZWT induced mitophagy in CGN through increasing the expression of LC3, and decreasing p62, HSP60, TOMM20, and ZWT also enhanced the colocation of LC3 to the mitochondria. We found that ZWT inhibited the PI3K/AKT/mTOR pathway, which could be disturbed by PI3K inhibitor LY294002 and agonist insulin-like growth factor 1. Moreover, ZWT reversed the inhibition of the AMPK pathway in CGN. Overall, ZWT ameliorated renal mitochondrial dysfunction probably by inducing mitophagy via the PI3K/AKT/mTOR and AMPK pathways.

Suppression of CCDC6 sensitizes tumor to oncolytic virus M1.

Oncolytic virus is an effective therapeutic strategy for cancer treatment, which exploits natural or manipulated viruses to selectively target and kill cancer cells. However, the innate antiviral system of cancer cells may resistant to the treatment of oncolytic virus. M1 virus is a newly identified oncolytic virus belonging to alphavirus species, but the molecular mechanisms underlying its anticancer activity are largely unknown. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. RNA seq analysis was used to analyze the gene alternation after M1 virus infection. Small interfering RNAs transfection for gene knockdown was used for gene functional tests. Caspase-3/7 activity was detected by Caspase-Glo Assay Systems. A mice model of orthotopic bladder tumor was established to determine the oncolytic effectiveness of the M1 virus. The expression of cleaved-Caspase 3 as well as Ki-67 in tumor cells were detected by immunohistochemical analysis. To further define the molecular factors involved in M1 virus-mediated biological function, we knocked down genes related to alphavirus' activity and found that CCDC6 plays an important role in the oncolytic activity of M1 virus. Moreover, knocked down of CCDC6 augments the reproduction of M1 virus and resulted in endoplasmic reticulum (ER) stress-induced cell apoptosis in vitro as well as in vivo orthotopic bladder cancer model. Our research provides a rational new target for developing new compounds to promote the efficacy of oncolytic virus therapy.

Laparoscopic transmesenteric pyeloplasty and isthmusectomy for adult horseshoe kidney with recurrent symptomatic hydronephrosis.

INTRODUCTION: There is no consensus for the horseshoe kidneys with recurrent symptomatic hydronephrosis, so we presented our initial experience with a laparoscopic transmesenteric approach. CASE PRESENTATION: Five patients with symptomatic ureteropelvic junction obstruction were identified by computed tomography urography. The laparoscopic transmesenteric approach was performed in such a way that the mesentery of the small intestine was incised along with the blood vessels longitudinally, and the isthmus was isolated to avoid injury to the mesenteric blood supply; then we cut the isthmus using an endostapler. The ureteropelvic junction obstruction was removed via the Anderson-Hynes technique. The operation time was 135-204 min, and the estimated blood loss was 50-120 mL. Patients had a 5.7-day stay postoperatively, there were no other injuries or complications, and ultrasound scans or computed tomography urography showed good postoperative effects. CONCLUSION: Laparoscopic transmesenteric surgery is a feasible and safe procedure for selected cases with horseshoe kidney with recurrent symptomatic hydronephrosis.

miR-197-3p Represses the Proliferation of Prostate Cancer by Regulating the VDAC1/AKT/ß-catenin Signaling Axis.

Accumulating investigations have demonstrated that microRNAs (miRNAs) are promising efficient targets for the next generation of molecular therapeutics. The development of miRNA-based therapies requires the identification and validation of cancer-associated miRNAs. Herein, we identified that miR-197-3p regulates the carcinogenesis and development of prostate cancer (PCa) via bioinformatics analysis. Next, we investigated the function and regulatory mechanisms of miR-197-3p in PCa. Overexpression of miR-197-3p suppressed PCa cell proliferation and colony formation. In contrast, inhibition of miR-197-3p activity enhanced PCa cell proliferation and colony formation. Mechanistic investigations identified that voltage dependent anion channel 1 (VDAC1) is a direct target of miR-197-3p. miR-197-3p targeting of VDAC1 resulted in downregulation of p-Akt and ß-catenin. Subsequently, we found that restoration of VDAC1 abolished the effects of miR-197-3p on PCa cell proliferation and AKT signaling pathway. Furthermore, we confirmed that miR-197-3p suppressed tumor xenograft growth in vivo. In conclusion, our study offers an empirical investigation of miR-197-3p, a tumor suppressor that may be a potential therapeutic target in PCa.

Statin and metformin therapy in prostate cancer patients with hyperlipidemia who underwent radiotherapy: a population-based cohort study.

PURPOSE: To evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan. SUBJECTS AND METHODS: Newly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000-2010. The survival rate was estimated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes. RESULTS: The study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09-0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45-18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes. CONCLUSION: The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

Impact and Predictive Value of Prostate Weight on the Outcomes of Nerve Sparing Laparoscopic Radical Prostatectomy in Patients with Low Risk Prostate Cancer.

PURPOSE: To investigate the impact of prostate weight on outcomes of nerve sparing laparoscopic radical prosta-tectomy (LRP) and assess its predictive value on postoperative continence and potency recovery. MATERIALS AND METHODS: We conducted a retrospective study on the clinical data of 165 patients with low risk prostate cancer (PCa) who underwent nerve sparing LRP. All the patients included had normal preoperative uri-nary and sexual function. The association of prostate weight with perioperative data was assessed using Spearman correlation coefficient. Univariate and multivariate Cox regression analyses were employed to identify prognostic predictors for continence and potency recovery. RESULTS: Increased prostate weight was significantly associated with older age, higher prostate-specific antigen (PSA), lower biopsy and pathological T stage and Gleason score, longer operative time, and higher estimated blood loss (P < .05). The continence rates at the 3rd, 6th, and 12th month after surgery were 63.6% (105/165), 87.9% (145/165), and 95.8% (158/165); and the potency rates were 44.8% (74/165), 62.4% (103/165) and 77.6% (128/165), respectively. Furthermore, multivariate Cox analysis showed that patient age (HR = 0.52, 95% CI: 0.35- 0.76) and prostate weight (HR = 0.54, 95% CI: 0.34-0.86) were independent predictors for continence recovery, while only patient age (HR = 0.66, 95% CI: 0.45-0.96) could independently predict potency recovery. CONCLUSION: Larger prostate size was correlated with older age, higher PSA, lower tumor stage and grade, longer operative time, and more intraoperative blood loss in low risk PCa patients. Increased prostate weight may inde-pendently predict poor continence recovery after nerve sparing LRP.

A modification with threading cannula needle-assisted 4-point suspension fixation for retroperitoneal laparoscopic pyeloplasty in children with ureteropelvic junction obstruction: a cohort study in single center.

PURPOSE: To evaluate the effect and safety of modifying a threading cannula needle-assisted suspension fixation in retroperitoneal laparoscopic dismembered pyeloplasty (LDP) for children with congenital ureteropelvic junction obstruction (UPJO). METHODS: Between December 2012 and December 2017, 45 children (< 14 years of age) with congenital UPJO were divided into two groups. In Group A, children underwent conventional "no-suspension fixation" LDP; and in Group B, "4-point suspension fixation" LDP was performed to lower difficulties and shorten operative time. The perioperative clinical data were recorded and analyzed. RESULTS: No statistical difference was found between two groups in preoperative characteristics. The duration of surgery, operative time for completion of anastomosis and the length of postoperative hospital stay in Group B was remarkably shortened than that in Group A, respectively (P < 0.05 for all). There was no significant difference between two groups in terms of postoperative renal pelvic diameter (RPD) decreasing, extubation time and success rates of surgery (P > 0.05 for all). In addition, no recurrent stenosis and urine leakage in both groups, and the postoperative RPD remained at the low level in both groups during the period of follow-up. CONCLUSIONS: Our modification of the 4-point suspension fixation for retroperitoneal LDP is an effective and safe method for children with UPJO. It can simplify the surgical procedures, lower difficulties (especially in precise anastomotic suturing) and shorten the learning curve. This modification might be of particular interest to urologists for improving treatment of children with UPJO.