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Introduction: Intra-vesical Prostatic Protrusion (IPP) has been reported to be associated with bladder outlet obstruction (BOO) and is the main cause of LUTS during the development of Benign Prostatic Hyperplasia (BPH). However, the molecular mechanism of IPP is still unclear. Methods: Clinical data analysis was performed to detect the association of IPP and long-term complications in patients with BPH. To explore the molecular mechanism of IPP formation, we performed RNA sequencing on prostate tissues (IPP or not) Stromal cells obtained from IPP-derived primary cultures. Cell proliferation was evaluated by CCK-8 assay. Multiple proteins in the signaling pathway were assessed using western blot. Results: Firstly, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, Fibroblast growth factor 7 (FGF7) was up-regulated in IPP tissues compared to normal prostate tissues through RNA sequencing. We observed that FGF7 was up-regulated in both IPP tissues and IPP primary stromal cells through IHC, Western-blot and qRT-PCR. Meanwhile, FGF7 expression is significantly up-regulated in high IPP grade prostate tissues. Down-regulation of FGF7 in IPP-derived stromal cells led to impairment of proliferation and migration of the prostate epithelial cells via co-culture experiments. Additionally, FGF7 induced the epithelial-mesenchymal transition (EMT) process through binding to FGFR2. RNA sequencing analysis also revealed the activation of MAPK/ERK1/2 signaling pathway. Moreover, down-regulation of MAPK/ERK1/2 by specific inhibitor impacted effects of FGF7 stimulation in vitro. Conclusions: Our data revealed a novel amplification effect, namely stromal cells derived FGF7 promotes epithelial cell proliferation as well as stromal cell phenotype which eventually induced IPP formation. And targeting FGF7 significantly reduced epithelial to stromal transition, also providing a potential therapeutic target for BPH progression.

PurposeThis study aimed to examine the research hotspots and evolution paths in the field of health information behavior (HIB) in China and abroad, and conduct comparative analysis to better understand its development trajectory globally.Design/methodology/approachA keyword search of the relevant literature included in the China National Knowledge Infrastructure (CNKI) database and Web of Science (WoS) core collection database was conducted, using the visualized analysis tool CiteSpace V for bibliometric analyses.FindingsThe common research hotspots in China and abroad can be divided into related research on HIB, research on its influencing factors and health information research. Among these, health information-seeking behavior has been the focus of domestic and foreign scholars. From the subdivision perspective, the focus of Chinese and foreign research hotspots differs. In terms of evolutionary path, the initial stage of HIB research in China and abroad revolves around health information and health information-seeking behavior, followed by the influencing factors of HIB; however, the research breakthrough point is the reverse. Then, domestic and foreign research was conducted on different types of HIBs. Regarding the selection of research objects, Chinese and foreign research objects were increasingly diversified.Research limitations/implicationsThis study also has several limitations. First, the literature sample only selected the literature in the WoS and CNKI databases, and there may be many HIB-related works published in other databases. Therefore, future research should include other databases. Second, in terms of language, this study selected only Chinese and English literature, but in many countries, important research results on certain topics are usually published in native language, and future research should expand the language selection. Third, this study only conducted national and institutional collaboration network analysis, keyword co-occurrence analysis, cluster analysis and timeline chart analysis.Practical implicationsThe implication of practice can be divided into the following three points. (1) Analyzing the domestic and foreign literature on HIB and identifying highly cooperative institutions and countries in the field of HIB can reveal the research situation of HIB and help researchers establish new research networks in the future. (2) Analyzing the research hotspots and evolutionary paths of HIB at home and abroad is helpful for quickly understanding the development context of this field and grasping the emerging research directions such as HIB of people in close contact with patients, health information exchange behavior, health information avoidance behavior and health information discontinuation behavior, which can help researchers to explore the future research direction in this field, so as to determine the topic and fill the research gap. (3) Combining the analysis of HIB-related research at home and abroad is helpful for professionals to understand the characteristics and rules of HIB of users, consumers and other groups to further optimize and improve health information services.Originality/valueComparing and summarizing the research status of HIB in China and globally, and presenting the findings visually, will help researchers better grasp the research overview and hotspot changes in this field, as well as provide a follow-up reference.

Extreme hypoxia is among the most prominent pathogenic features of pancreatic cancer (PC). Both the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and hypoxic inducible factor-1α (HIF-1α) are highly expressed in PC patients and play a crucial role in disease progression. Reciprocal regulation involving PVT1 and HIF-1α in PC, however, is poorly understood. Here, we report that PVT1 binds to the HIF-1α promoter and activates its transcription. In addition, we found that PVT1 could bind to HIF-1α and increases HIF-1α post-translationally. Our findings suggest that the PVT1‒HIF-1α positive feedback loop is a potential therapeutic target in the treatment of PC.

Background To identify risk factors by developing a nomogram for predicting surgical outcomes for female patients who underwent tension free vaginal tape (TVT) for stress urinary incontinence (SUI). Methods Data on 365 patients with pure SUI who underwent TVT at the Shanghai General Hospital between February, 2017 and July, 2018, were retrospectively collected. Within this group, symptoms of patients who were found to have disappeared or have been improved (subjective success group) were compared with symptoms of those patients who were found to have no change or recurrence (subjective failure group). We evaluated the effect of treatment after TVT surgery on SUI patients based upon patient prognosis. Results During the study period, 327 women underwent TVT surgery and met the qualifications for inclusion in six-month follow-up consultations and 38 patients were lost. Multivariable logistic regression analysis of risk factors that were important in relation to the failure of surgery indicated two independent predictors: total cholesterol (TC) (P=0.005) and maximal urethral closure pressure (MUCP) (P=0.028). We developed a nomogram to predict prognosis after TVT in female patients with SUI using these parameters. Conclusions We developed a predictive model for preoperative estimation of prognosis in female patients who underwent TVT based treatment for SUI. This model could select patients who were found to have successful postoperative outcomes, which can lead to a rational therapeutic choice.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive platelet disorder due to a qualitative or quantitative anomaly of the platelet membrane glycoprotein GPIIb/IIIa. Its clinical manifestations include mild to severe bleeding. GT diagnosis mainly depends on platelet function analysis, flow cytometry, and gene detection. Treatment methods include conservative symptomatic treatment and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT is the only clinical radical method for GT. Herein, we report a 2-year-old boy with GT successfully cured by related identical peripheral blood stem cell transplantation (PBSCT). The platelet disorder was corrected to a normal level after PBSCT, with no significant complication related to the transplantation. Hematopoietic stem cell transplantation with full-matched donor in early stage could be a treatment option for GT.

Dan Yu,1,&ast; Di-Xiao Yang,2,&ast; Yao Li,3 Bi Guan,2 Qian Ming,2 Yan Li,2 Yi-Ping Zhu,4 Li-Qing Chen,1 Wei-Xiang Luo5 1Department of Otolaryngology and Hepatobiliary, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 2Nursing Department, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 3Intensive Care Unit, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 4Department of Oncology, Chengdu Wenjiang District People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 5Department of Nursing, Shenzhen People’s Hospital (2nd Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Xiang LuoDepartment of Nursing, Shenzhen People’s Hospital (2nd Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of ChinaTel +86 755-25533018-2887Email luoweixiang688@hotmail.comBackground: Due to the poor healing of superficial malignant tumor ulcer wounds, patients suffer great pain and significantly reduced quality of life. Related research shows that oxygen therapy can reduce wound bleeding and promote wound healing.Objective: This study aims to explore the therapeutic effect of nano-silver antibacterial dressing combined with high-flow oxygen therapy on surface malignant tumor ulcers.Methods: In this retrospective analysis, 64 patients with superficial malignant tumors and ulcer infection were included and divided into the research group and the control group, with 32 cases in each group. After conventional debridement, the control group was treated with vaseline dressing, while the research group was treated with nano-silver medical antibacterial dressing combined with high-flow oxygen therapy. Both groups were treated for 7 days. The frequency of dressing change and the number of times of blood oozing between the two groups after treatment were recorded. The pain, clinical efficacy, and levels of procalcitonin (PCT) and C-reactive protein (CRP) were compared between the two groups before and after treatment.Results: The dressing changes and blood oozing were less frequent in the research group compared with the control group. The pain score and the levels of PCT and CRP in the research group were lower than those in the control group. The overall response rate was significantly higher in the research group as compared to the control group. All the above differences were statistically significant (P< 0.05).Conclusion: Nano-silver medical antibacterial dressing combined with high-flow oxygen therapy can reduce the frequency of dressing changes in patients, relieve pain, reduce inflammation, and accelerate the healing of superficial malignant tumor ulcer wounds.Keywords: nano-silver medical antibacterial dressing, high flow oxygen therapy, body surface malignant tumor, ulcer, wound

BACKGROUND Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and it commonly expresses peptide and protein factors that are active as hormones. These secreting factors manifest as paraneoplastic disorders, such as ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). The clinical features are abnormalities in carbohydrate metabolism, hypokalemia, peripheral edema, proximal myopathy, hypertension, hyperpigmentation, and severe systemic infection. However, it is uncommon that EAS has an influence on hypothalamus-pituitary function. CASE SUMMARY A 62-year-old man presented with complaints of haemoptysis, polyuria, polydipsia, increased appetite, weight loss, and pigmentation. Following a series of laboratory and imaging examinations, he was diagnosed with SCLC, EAS, hypogonadism, hypothyroidism, and central diabetes insipidus. After three rounds of chemotherapy, levels of ACTH, cortisol, thyroid hormone, gonadal hormone, and urine volume had returned to normal levels. In addition, the pulmonary tumor was reduced in size. CONCLUSION We report a rare case of SCLC complicated with panhypopituitarism due to EAS. We hypothesize that EAS induced high levels of serum glucocorticoid and negative feedback for the synthesis and secretion of antidiuretic hormone from the paraventricular nucleus, and trophic hormones from the anterior pituitary. Therefore, patients who present with symptoms of hypopituitarism, or even panhypopituitarism, with SCLC should be evaluated for EAS.

Objective: To study the correlation between ultrasound Tei index and cardiac injury in cancer patients after thoracic radiotherapy. Methods: The 78 patients with malignant tumor who received thoracic radiotherapy in Mianyang Central Hospital, Sichuan, China between February 2015 and March 2018 were selected as observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as control group. The observation group underwent cardiac ultrasonography before and after radiotherapy to calculate Tei indexes and serum was collected to determine cardiac injury markers, inflammatory cytokines and oxidative stress mediators, while the control group underwent cardiac ultrasonography during the physical examination to calculate Tei indexes and serum was collected to determine cardiac injury markers, inflammatory cytokines and oxidative stress mediators.Results: Left cardiac Tei index, right cardiac Tei index as well as serum creatine phosphokinase, creatine phosphokinase isoenzyme, troponin I, interferon-induced protein-10, interleukin-6, interleukin-10, transforming growth factor-β1 and 8-hydroxy-2-deoxyguanosine contents of the observation group after radiotherapy were significantly higher than those before radiotherapy and those of the control group (P

We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-β expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14–18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-β1 and EMT markers. In rat kidney tubular epithelial cells (NRK52E), ROS production increased expression levels of TGF-β1 and subsequently contributed to the induction of Snail1-mediated EMT. Notably, DBP exposure also promoted autophagy that downregulated TGF-β1. Taken together, our findings suggest that maternal exposure to DBP promotes EMT in tubular epithelial cells via upregulation of TGF-β1.

Background: Until recently, most enucleation techniques of the prostate were performed with the application of morcellator. We introduce a modified enucleation technique of thulium laser with non-morcellator approach, which is about incising and vaporizing remaining prostate tissue instead of a morcellator.Methods: A retrospective evaluation of 223 patients undergoing ThuLEP from January 2014 to December 2015 was performed in our institution. One hundred five of the patients used morcellator while the other 118 used non-morcellator approach. All patients were assessed with the International Prostate Symptom Score (IPSS), quality of life (Qol), ultrasonography, serum prostate-specific antigen (PSA), maximal urine flow rate (Qmax), and postvoid residual urine volume (PVR). We reassessed these parameters at 1-, 3-, 6-, and 12-months after operation. Operative time, perioperative, and postoperative complications were also recorded.Results: Significant improvement was noted in the IPSS, QoL, Qmax, and PVR in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. Comparisons of the total operation time and enucleation time demonstrated no significant differences between the two groups. Our non-morcellator approach needed more time to incise and vaporize the enucleated tissue compared to morcellation when the prostate volume was about 40–80 ml (p < 0.05), while it showed a significant lower rate of superficial bladder injury than using morcellator (p < 0.05). There were no significant differences in other complications between the two groups (p > 0.05).Conclusions: Our modified technique is a safe and effective procedure for the treatment of BPH avoiding the potential complications caused by morcellator.

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.

BACKGROUND: This study aimed to assess the prognostic value of a various of diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer (BC) undergoing radical cystectomy (RC).METHODS: IHC was performed on tumor specimens from 366 patients with transitional cell BC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with BC. The Kaplan–Meier estimate was performed to assess DFS, and univariate and multivariate Cox regression models were used to identify independent risk factors to predict DFS of patients with BC.RESULTS: Based on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (70.7%) compared with high-risk patients (17.9%) (p＜0.001); in the validation cohort, the 10-year DFS was 85.7% for the low-risk group and 20.4% for the high-risk group (p＜0.001). Multivariable Cox regression analyses showed that the high-risk group based on the nine-IHC-based classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the nine-IHC classifier and clinicopathological factors was developed for clinical application.CONCLUSION: The nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of BC.

Background Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression. Methods The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo. Results We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo. Conclusions Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0884-2) contains supplementary material, which is available to authorized users.

To compare the efficacy and safety of thulium laser VapoResection of the prostate (ThuVaRP) versus standard traditional transurethral resection of the prostate (TURP) or plasmakinetic resection of prostate (PKRP) for benign prostatic obstruction. Systematic searches were performed in the Medline, EMBASE, the Cochrane Library, Web of Science, and CNKI in December 2017. The outcomes of demographic and clinical characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were assessed. 16 studies were selected in the meta-analysis including nine randomized controlled trials (RCTs) and seven non-RCTs. Among of them, nine studies compared ThuVaRP with PKRP, while seven studies compared ThuVaRP with TURP. It seemed that ThuVaRP needed longer operation time than TURP (WMD = 6.41, 95% CI 1.38–11.44, p = 0.01) and PKRP (WMD = 10.15, 95% CI 5.20–15.10, p

Background Increased prostatic smooth muscle tone and hyperplastic growth contribute to urethral obstruction and voiding symptoms in benign prostatic hyperplasia (BPH). It has been suggested that different proliferative potential of stromal cells between transition zone (TZ) and adjoining regions of the prostate plays a significant role in the development of BPH. However, the molecular mechanisms of this hyperplastic process remain unclear. We found tumor necrosis factor receptor-associated factor 6 (TRAF6) highly expressed in TZ stromal cells compared to peripheral zone (PZ) stromal cells by gene array analyzes. Therefore, we aim to study the potential mechanisms of stromal TRAF6 in promoting BPH progression. Methods Stromal cells obtained from BPH-derived primary cultures. The TRAF6-siRNA vector were constructed and transfected into cultured human BPH primary TZ stromal cells, and TRAF6-overexpressing vector were constructed and transfected into cultured human BPH primary PZ stromal cells. Stromal cells were recombined with BPH-1 cells then subcutaneously inoculated into the kidney capsule of male nude mice. Cell proliferation was evaluated by CCK-8 assay. Multiple proteins in the Akt/mTOR pathway were assessed using western blot. Results TRAF6 levels were increased in TZ stroma compared with PZ stroma of BPH. The in vitro cell culture and in vivo cell recombination revealed that selective downregulation of TRAF6 in TZ stromal cells led to suppression of the proliferation, while upregulation of TRAF6 in PZ stromal cells enhanced the proliferation. We found that the Phosphorylation and Ubiquitination of Akt as well as the Phosphorylation of mTOR, P70S6K were decreased when TRAF6 was downregulated in primary cultured TZ stromal cells of BPH. Conclusions TRAF6 can promote the proliferation of stromal cells of BPH via Akt/mTOR signaling. Our results may make stromal TRAF6 responsible for zonal characteristic of BPH and as a promising therapeutic strategy for BPH treatment.

Laparoscopic distal gastrectomy (LDG) for gastric cancer has gradually gained popularity. However, laparoscopic total gastrectomy (LTG) has been reported rarely when compared with LDG. This study was designed to evaluate the surgical outcomes as well as the morbidity and mortality of LTG compared with LDG to confirm the feasibility and safety of LTG.We reviewed the data of patients at our institution undergoing LTG (n = 448) or LDG (n = 956) for gastric cancer between January 2008 and July 2016. Then the clinical characteristics and perioperative clinical outcomes of the two groups were compared.Except for tumor size and stage, there were no statistically significant differences in the clinicopathological parameters between the groups. LTG was associated with significantly longer operation time, late time to postoperative diet, and longer hospital stay compared with the LDG group. Overall complications developed in 60 patients (13.4%) and surgical complications in 48 patients (10.7%) after LTG. Postoperative complications were less frequent in the LDG group than in the LTG group (8.4% versus 13.4%, p .01), and fewer surgical complications were observed with LDG than with LTG (7.5% versus 10.7%, p = .05).The results of LTG were favorable even though are not inferior to those of LDG. LTG for gastric cancer is technically feasible and safe. However, because of the limits of this study, other high-quality studies are needed for further evaluation.

// Yi-Ping Zhu 1, * , Lei Chen 1, * , Xing-jie Wang 1, * , Qi-Heng Jiang 3, * , Xiao-Yu Bei 1 , Wen-Lan Sun 2 , Shu-Jie Xia 1 , Jun-Tao Jiang 1 1 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China 2 Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China 3 Medical Services Section, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China * These authors contributed equally to this work Correspondence to: Jun-Tao Jiang, email: jjturologist@126.com Shu-Jie Xia, email: xsjurologist@126.com Keywords: renal fibrosis, kidney dysplasia, di-n-butyl phthalate (DBP), oxidative stress, environmental endocrine-disrupting compounds (EEDs) Received: November 30, 2016 Accepted: March 01, 2017 Published: March 10, 2017 ABSTRACT This study was to determine the impact of maternal exposure to di-n-butyl phthalate (DBP) on renal development and fibrosis in adult offspring. Pregnant rats received DBP at a dose of 850 mg/kg BW/day by oral perfusion during gestational days 14–18. In DBP exposed newborn offspring, gross observation and histopathological examination revealed the dysplasia of kidney. The expression of genes related to renal development was also changed. In DBP exposed adult offspring, histopathological examination and Masson’s trichrome staining revealed the pathological changes of renal fibrosis. Furthermore, higher expression levels of transforming growth factor- β (TGF-β) and alpha-smooth muscle actin (α-SMA) were also detected. In vitro studies reveal that DBP promoted the activation of NRK49F cells and G2/M arrest in NRK52E cells at a sublethal dose. The effect of DBP on these cell lines was linked to the generation of oxidative stress. In addition, DBP induced oxidative stress in both renal fibroblasts and tubular epithelial cells, whereas vitamin C ameliorated the changes caused by DBP. In conclusion, our results showed that prenatal exposure to DBP may generate oxidative stress in both renal fibroblasts and tubular epithelial cells, leading to kidney dysplasia and renal fibrosis.

// Lei Chen 1, * , Ming-Lei Sha 2, * , Deng Li 1, * , Yi-Ping Zhu 1 , Xing-Jie Wang 1 , Chen-Yi Jiang 1 , Shu-Jie Xia 1 , Yi Shao 1 1 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Department of Geriatric, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China * These authors are contributed equally to this work Correspondence to: Yi Shao, email: drshaoyi@163.com Keywords: renal fibrosis, relaxin, Toll-like receptor 4, macrophage polarization Received: November 08, 2016 Accepted: February 07, 2017 Published: February 18, 2017 ABSTRACT Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit the CKD process, it is important to prevent renal fibrosis, though CKD remains incurable. Renal fibrosis can be inhibited by relaxin in several experimental models, but the mechanism of relaxin for antifibrotic potential is still not clear. And here we have studied the role of relaxin in macrophage polarization and renal inflammation after unilateral ureteral obstruction (UUO). Our results show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling, shift macrophage polarization toward the M2 phenotype and ameliorat renal fibrosis in the early stages of UUO. In vitro experiments, it has been confirmed that relaxin can downregulate the TLR4 signaling and induce the M2 macrophage transition. Furthermore, the transitional actions of macrophage phenotype induced by relaxin are significantly blocked by TAK-242, a TLR4 antagonist, in vitro experiments. Thus, there is a novel mechanism of relaxin for antifibrosis that shifts macrophage polarization toward the M2 phenotype via inhibition of TLR4 signaling.

BACKGROUND Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate © 2017 Wiley Periodicals, Inc.

Di-n-butyl phthalate (DBP) is a pollutant that is widely present in the environment. We have previously demonstrated that maternal exposure to DBP resulted in renal fibrosis in offspring, but the underlying mechanism was not well elucidated. Therefore, the current study aims to understand the underlying molecular mechanisms in these sex-specific developmental alterations. Here, we used RNA-seq analysis to explore the underlying molecular mechanisms of DBP-associated renal fibrosis. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14–18. Upregulated autophagy in renal tubules in offspring was confirmed in the DBP-treated group via accessing LC3Ⅱ/Ⅰ protein expression. Increased expression of the HhIP gene was found in the DBP-treated group via RNA-seq analysis. Immunohistochemistry (IHC) staining and Western blot analysis confirmed increased expression of HhIP protein and inhibited hedgehog signaling. Increased HhIP expression further leaded to impaired activation of hedgehog signaling, which is critical for normal embryonic development. Additional in vitro experiments on renal tubular cells suggest that inactivation of hedgehog signaling induced autophagy in renal tubular cells. Taken together, our findings show that maternal exposure to DBP induced autophagy through regulation of hedgehog signaling via overexpression of HhIP in foetal renal tubular cells, which may be essential for renal fibrosis development.

Objective This study focused on the oxidative stress effect of di-n-butyl phthalate (DBP) on development of the urinary system. Methods We examined the mRNA expression of genital tubercle (GT) in control and DBP induced hypospadias group by Affymetrix Rat 230 2.0 Array. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of inositol-1,4,5-triphate-receptor (IP3R) and epithelial-mesenchymal-transition (EMT)-related molecular markers, such as E-cadherin, β-Catenin, Snail, N-cadherin, in the GT of hypospadiac male rats and controls. The results of array were further confirmed in vitro. The changes of intracellular calcium concentration in urethral epithelial cells were detected by Fluo-3-AM before and after DBP treatment. The levels of reactive oxygen species (ROS) in urethral epithelial cells were measured by DCFH-DA with different concentrations of DBP (0, 1, 10, 100 μmol/L) treatment. Results The mRNA expression profiles of GT in control and DBP induced hypospadias group showed high expression of IP3R and the abnormalities of EMT. Compared to the control group, the expression levels of IP3R, E-cadherin and β-Catenin increased at both the protein and mRNA levels. However the expression levels of Snail and N-cadherin decreased. The intracellular calcium concentration increased significantly after DBP treatment. The effect of DBP on urethral epithelial cells was linked to the generation of oxidative stress. Conclusion DBP can influence the development of GT through its oxidative stress effect, which significantly increases the concentration of calcium and inhibits EMT in urethral epithelial cells, and block the fusion process of urethral groove, causing the occurrence of hypospadias. This study provides a new understanding of DBP's molecular mechanisms on hypospadias and may lead to new treatment strategies for the disease.

The study focused on the toxicological effect of Di-n-butyl phthalate (DBP) on the expression of Phosphorylated signal transducer and activator of transcription 1 (pSTAT1) -regulated Forkhead box protein M1 (FoxM1), which might provide a new understanding of gestational diabetes mellitus (GDM) development and a potential target for treatment. Streptozotocin (STZ) (40 mg/kg) was introduced in maternal rats by intraperitoneal injection on gestation day 0 (GD 0) in the STZ and STZ + DBP groups. DBP was introduced in maternal rats by oral feeding in the STZ + DBP group over the following 3 days (750 mg/kg/day). The changes in fasting blood glucose level in rats were detected on GD 1 and GD 5. The insulin levels in maternal rats and PIBCs were measured on GD 18. The Oral Glucose Tolerance Test (OGTT) test was performed on GD 18 to check the stability of the GDM model. The primary islet β cells (PIBCs) were established for in vitro experiments. We examined the FoxM1 and pSTAT1 expression in pancreas by immunohistochemistry. Real-time PCR and Western blot were used to detect the pSTAR1 and FoxM1 protein and mRNA gene expression levels in PIBCs. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis was used to test the viability and apoptosis of cells. The results showed that the STZ + DBP group had higher glucose and lower insulin secretion levels than the other groups by both fasting test and OGTT. FoxM1 was significantly suppressed while pSTAT1 was highly expressed after DBP exposure. FoxM1 could be regulated by pSTAT1. DBP can influence the progression of GDM through its toxicological effect, which significantly increases the expression of pSTAT1 and suppresses FoxM1, causing a decline in β cell viability.

This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP.

Previous study have demonstrated that not only the anorectal development but also the general conditions of anorectal malformations (ARMs) male rats are severely affected by di-n-butyl phthalate (DBP) maternal exposure. However, the mechanisms underlying DBP-induced congenital defects remain elusive. Reportedly, Fgf10/Fgfr2 and androgen receptor (AR) are pivotal for the development of multiple organs. In this study, we therefore investigated the expression of Fgf10/Fgfr2 together with AR in the terminal rectum and multiple organs of ARM male rats induced by in utero exposure to DBP. DBP was administered to pregnant rats to establish the model and the incidence of ARMs in male offspring was 39.5%. On postnatal day(PND)1, the gross photograph and histopathological staining confirmed the abnormal manifestations in these organs of newborn ARMs. Decreased anogenital distance, body weight and serum testosterone level were observed in ARM male offspring. The reduced expression of Fgf10/Fgfr2 mRNA and protein was seen in terminal rectum and kidney, spleen, liver, heart in ARM male rats, whereas the reduced expression of AR was only observed in the kidney and terminal rectum. Our findings suggest the potential involvement of altered Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP.

Objectives 5α‐reductase inhibitor (5‐ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. Materials and Methods Prostate specimens from patients were collected. Insulin‐like growth factor 1 (IGF‐1), Beclin‐1, LC3 levels, was analysed by immunohistochemistry. The role IGF‐1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. Results We demonstrated that IGF‐1 expression is down‐regulated in prostate fibroblasts after long‐term 5‐ARI application. A decrease in IGF‐1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF‐1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long‐term 5‐ARI application reduces IGF‐1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. Conclusions Focusing on the autophagy induced by low levels of IGF‐1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.

Maternal exposure to di-n-butyl phthalate (DBP) induces hypospadias via regulation of autophagy in uroepithelial cells. Here, we use gene express analysis to explore the underlying molecular mechanisms. Pregnant rats received DBP orally at a dose of 750 mg/kg/day during gestational days 14–18. Gene expression analysis showed an increased expression of the hedgehog interacting protein (HhIP) gene. In DBP-induced hypospadiac male offspring, immunohistochemistry (IHC) staining and Western blot analysis confirmed increased expression of the HhIP protein and inhibited hedgehog signaling. in vitro experiments suggest the involvement of the reactive oxygen species (ROS)-HhIP-Gli1-autophagy axis in DBP-treated primary rat urethral epithelial cells. Taken together, our findings show that prenatal exposure to DBP induces abnormal hedgehog signaling and autophagy in uroepithelial cells that may play important roles in the development of hypospadias.

To understand the heavy metals content such as As, Cd, Cr, Cu, Hg, Pb, and Zn, as well as their distribution features in surface sediments of tidal flat areas of Eastern China, mathematical statistics, correlation analysis, factor analysis and other statistical methods are used. This study collected 1906 surface sediment samples of As, Cd, Cr, Cu, Hg, Pb, Zn were collected as part of a systematic research effort. These results show that the coastal tidal flats zone of Eastern China contains surface sediment samples with heavy metal concentrations (As, Cd, Cr, Cu, Hg, Pb, and Zn) with is not high but has increased due to anthropogenic sources. The total content of heavy metals in Jiangsu province is low, however, in Shanghai and Zhejiang provinces relatively high heavy metal contents are present. In addition to natural causes, the heavy metal content in coastal sediment in Shanghai and Zhejiang is significantly affected by human activities, while Jiangsu coastal surface sediments has light impacts from human activities. Heavy metal contamination in coastal areas Shanghai, Zhejiang, and Fujian provinces is particularly serious including Hg, Cd, and Cu contamination. The results of an evaluation using the Marine Pollution Sediment Index and Mean Sediment Quality Guidelines show that in Eastern China, the overall sediment pollutant ecological risk is low for Jiangsu and Fujian provinces, however, the ecological risk for the tidal flats of Shanghai and Zhejiang provincial beaches is relatively high due to heavy metal concentrations.

Maternal exposure to di-n-butyl phthalate (DBP) induces hypospadias, but the underlying mechanisms remain elusive. Here we hypothesize that aberrant activation of autophagy and epithelial-mesenchymal transition (EMT) are the leading cause of DBP-related hypospadias. Pregnant rats received DBP orally at a dose of 750 mg/kg/day during gestational days 14–18. In DBP-induced hypospadiac male offspring, immunohistochemistry (IHC) staining and Western blot showed increased expression of autophagy and EMT markers in genital tubercle (GT) tissue compared to the control. In addition, lower testosterone levels and androgen receptor (AR) expression in GT tissue were detected. In vitro studies revealed that impaired AR signaling was involved in DBP-induced autophagy and autophagy activation furthermore promoted EMT in urethral epithelial cells. DBP combined with chloroquine, an autophagy inhibitor, reduced the expression of EMT markers compared with DBP treatment alone, while DBP combined with the autophagy inducer rapamycin elevated the expression of EMT markers. The autophagy-lysosomal pathway inhibitor CQ but not proteasome inhibitor MG-132 rescued the decrease of E-cadherin after DBP treatment, which indicated autophagy-induced E-cadherin degradation contributes to DBP-related EMT. Taken together, our findings show that prenatal exposure to DBP induces abnormal autophagy and EMT that may play important roles in hypospadias development.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and its mechanisms have not been clearly elucidated. A large percentage (more than 95%) of cases are late-onset AD without familial traits. Although some genes have been implicated in the pathogenesis and the risk of developing sporadic AD, they only account for the minority of late-onset AD. Recently, accumulating data have suggested a potential role for epigenetic mechanisms in neurodegenerative processes leading to dementia. Alterations in the epigenetic machinery cause aberrant DNA methylation and histone acetylation. Therefore, these changes trigger alterations on the transcriptional level of genes involved in the pathogenesis of AD. In this review, we summarize recent advances in research on AD caused by common epigenetic modification and the potential treatment strategies targeting the epigenetic machinery.

In a multicenter study, we have conducted a retrospective study on 73 pediatric AML patients who were primary refractory or in greater than CR1 and investigated MSD (or MMSD) (n = 20), URD (n = 23), and UCB (n = 30) HCT between January 1998 and October 2009. The median day to neutrophil engraftment was similar in all groups. The median day to platelet engraftment was longer in the UCB group. The number of HLA mismatch was higher in the UCB group (p = 0.034); however, the cumulative incidence of grade III-IV aGVHD was not different among all groups (p = 0.125); furthermore, cGVHD was lower in the UCB group (p = 0.078). The risk of relapse did not differ among all groups (RR = 1.28, p = 0.125), but the patients of MSD (or MMSD) grafts had a trend of higher risk recurrence. Sixty-two patients survived with a median follow-up of 58.2 months. Five-yr LFS was 73.1%, 59.8%, and 59.6% for URD, UCB, and MSD (or MMDS), respectively (p = 0.426). Five-yr LFS in CR1 was 68.9%, with a significantly better result compared to 41.7% in CR2 (p = 0.025). Our comparisons suggest that pediatric AML patients receiving UCB had a higher early TRM, a lower cGVHD rate, and a similar long-term survival. The outcome of URD and UCB is comparable to that of a suitable sibling for pediatric AML.

Objectives Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. Materials and methods TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. Results Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. Conclusion Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization.

Background We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) induces dysplasia of the kidney in newborn male offspring and renal fibrosis in adults. But the underlying mechanisms remain elusive. Fgf10/Fgfr2 and androgen receptor (AR) are known to be important for renal development. We therefore investigated whether these genes are involved in DBP-induced renal fibrosis. Materials and methods Using Sprague-Dawley rats and rat renal proximal tubular cells (NRK52E), we determined the potential involvement of Fgf10, Fgfr2 and AR in DBP-induced renal fibrosis. Results We found that maternal exposure to DBP induces renal fibrosis in adult male offspring. A lower serum testosterone concentration and reduced expression of Fgf10, Fgfr2 and AR were detected in these animals. These was a trend toward lower expression of Fgf10, Fgfr2 and AR in NRK52E cells subjected to DBP exposure. Furthermore, higher expression levels of TGF-β and α-SMA were observed in abnormal renal tissue and DBP-treated NRK52E cells. Conclusion Our findings suggest the potential involvement of Fgf10/Fgfr2 and AR in renal fibrosis of adult male rat offspring induced by prenatal exposure to DBP. The anti-androgenic effects of DBP might play an important role in this pathological process.

// Dian-Jun Yu 1, 4, * , Xing-Jie Wang 2, * , Yun-Feng Shi 1, 5, * , Chen-Yi Jiang 2 , Rui-Zhe Zhao 2 , Yi-Ping Zhu 2 , Li Chen 4 , Yuan-Qing Yang 4 , Xiao-Wen Sun 1, 2, 3 and Shu-Jie Xia 1, 2, 3 1 Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China 2 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China 3 Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China 4 Department of Urology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo 315048, China 5 Department of Urology, Wujin Hospital Affiliated Jiang Su University, Changzhou 213302, China * These authors contributed equally to this work Correspondence to: Shu-Jie Xia, email: xsjurologist@163.com Xiao-Wen Sun, email: sunxiaow1973@163.com Yuan-Qing Yang, email: easternurology@163.com Keywords: benign prostatic hyperplasia, wound healing, retinoic acid, RARβ, macrophage Received: March 13, 2017 Accepted: May 10, 2017 Published: May 26, 2017 ABSTRACT BACKGROUND: The wound-healing process is very important for reducing complications after thulium laser resection of the prostate (TmLRP). The retinoic acid (RA) signaling pathway has been well studied in the wound-healing process of the skin and other organs. The goals of this study were to identify the role of RA signaling in the repair of the prostate after TmLRP and to investigate the molecular mechanism of this process. RESULTS: Retinoic acid receptors (RARs) were present in the prostate, and their expression was increased after TmLRP. RARβ was expressed in the macrophages and may be related to the role of stromal cells in the wound-healing process. In vitro, RA enhanced the function of anti-inflammatory macrophages and promoted stromal cell activation and angiogenesis. Arg1 was also increased via RARβ after treatment with RA. MATERIALS AND METHODS: The expression of RARs was analyzed in vivo by immunohistochemistry (IHC), real time qPCR, and western blot analysis. THP-1 cells were co-treated with or without RA and stimulating factor and then assessed by ELISA and qPCR. The supernatants from these cells were cultured with stromal cells and vascular endothelial cells, and the effects on these cells were analyzed. CONCLUSIONS: We found that RA signaling was involved in the wound-healing process of the prostate after TmLRP. RA treated macrophages activated stromal cells and promoted angiogenesis. RARβ was the key isoform in this process.

Background Obesity is a growing epidemic around the world, and obese patients are generally regarded as high risk for surgery compared with normal weight patients. The purpose of this study was to evaluate the influence of obesity on the surgical outcomes of laparoscopic gastrectomy (LG) for gastric cancer. Methods We reviewed data for all patients undergoing LG for gastric cancer at our institute between October 2004 and December 2016. Patients were divided into non-obese and obese groups and the perioperative outcomes were compared. Furthermore, a subgroup analysis was conducted to evaluate which of the two commonly used methods of LG, laparoscopic-assisted gastrectomy (LAG) and totally laparoscopic gastrectomy (TLG), is more suitable for obese patients. Results A total of 1691 patients, 1255 non-obese and 436 obese or overweight patients, underwent LG during the study period. The mean operation time was significantly longer in the obese group than in the non-obese group (209.9 ± 29.7 vs. 227.2 ± 25.7 min, P

To assess the efficacy and safety of thulium laser versus standard transurethral resection of the prostate (TURP) for treating patients with benign prostatic obstruction.A systematic search of the electronic databases, including Medline, Embase, Web of Science, and The Cochrane Library, was performed up to February 1, 2014. The pooled estimates of demographic and clinical baseline characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were calculated.Seven trials assessing thulium laser versus standard TURP were considered suitable for meta-analysis including four randomized controlled trials (RCTs) and three non-RCTs. Compared with TURP, although thulium laser prostatectomy (TmLRP) needed a longer operative time [weighted mean difference (WMD) 8.18 min; 95 % confidence interval (CI) 1.60-14.75; P = 0.01], patients having TmLRP might benefit from significantly less serum sodium decreased (-3.73 mmol/L; 95 % CI -4.41 to -3.05; P0.001), shorter time of catheterization (WMD -1.29 days; 95 % CI -1.95 to -0.63; P0.001), shorter length of hospital stay (WMD -1.83 days; 95 % CI -3.10 to -0.57; P = 0.005), and less transfusion (odds ratio 0.09; 95 % CI 0.02-0.41; P = 0.002). During the 1, 3, and, 12 months of postoperative follow-up, the procedures did not demonstrate a significant difference in IPSS, QoL, Qmax, and PVR.TmLRP had a similar efficacy to standard TURP in terms of IPSS, QoL, Qmax, and PVR, and offered several advantages over TURP in terms of blood transfusion, serum sodium decreased, catheterization time, and hospital stay, while TURP was superior in terms of operation duration. Well-designed multicentric/international RCTs with long-term follow-up are still needed.

Project invested with a type of Energy Performance Contracting has many stakeholders and its structure is complex. Risk factors produced from it are so widespread that its hard to control the risks of EPC project. Analyzing EPC project risks with interpretive structural model, solving reachability matrix and establishing Interpretive Structural Model to identify the relationship between factors and the surface, middle and deep risk factors affecting EPC project based on determination of risks, which provides a reference for policies and measures formulation of the relevant departments.

Objectives Prostate cancer is one of the most frequent malignancies in men, worldwide, although its underlying mechanisms are not fully understood. Long non-coding RNAs participate in development of human cancers. In this invetsigation, we aimed to study the roles of lincRNA-p21 in development of human prostate cancer. Materials and methods Expression of lincRNA-p21 was assessed by real-time PCR in cell lines and in human tissues. Lentivirus carrying sh-lincRNA-p21, lincRNA-p21 or control constructs were used to determine their effects on cell proliferation and apoptosis. A mouse xenograft model was employed to explore the functions of lincRNA-p21 on cancer cell population growth in vivo. Relationships between p53 downstream genes and lincRNA-p21 levels were explored by real-time PCR, western blotting and chromatin immunoprecipitation. Results LincRNA-p21 was found to be down-regulated in human prostate cancer, and low levels of lincRNA-p21 correlated with high disease stage and prediction of poor survival. We further showed that lincRNA-p21 inhibited prostate cancer cell proliferation and colony formation in vitro and reduced rate of prostate cancer cell population growth in vivo. Study of mechanisms involved revealed that lincRNA-p21 promoted apoptosis and induced expression of p53 downstream genes by regulating p53 binding to their promoters. Finally, we showed that expression of p53 downstream genes was reduced in the malignant prostate tissues, which correlated with lincRNA-p21 level. Conclusions Our findings indicated that lincRNA-p21 inhibited development of human prostate cancer partly by regulating p53 downstream gene expression and partly by apoptotic activation.