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Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical Abstract

Li Wang,1 Nie Hu,1 Zhongjun Jiang,1 Ping Luo,1 Nian Yi,1 Yanhua Chen,2 Ning Zhou,2 Longfei Liu2 1Department of Breast Surgery, Nanhua Hospital, Nanhua University, Hengyang City, Hunan Province, 421002, People’s Republic of China; 2Department of General Surgery, Nanhua Hospital, Nanhua University, Hengyang City, Hunan Province, 421002, People’s Republic of ChinaCorrespondence: Longfei LiuDepartment of General Surgery, Nanhua Hospital, Nanhua University, No. 336, Dongfeng South Road, Hengyang City, Hunan Province, 421002, People’s Republic of ChinaTel +86 0734-8399028Email liulongfei1977@aliyun.comBackground: Patients with cancer have a higher incidence of cardiovascular diseases (CVDs). We aimed to evaluate the relationship between serum human epididymal protein 4 (HE4) levels and cardiovascular events in obese patients with breast cancer.Methods: Serum HE4 levels in 316 obese patients with breast cancer were measured at baseline and then prospectively followed up for approximately 36 months. The prognostic value of serum HE4 for predicting cardiovascular events was analyzed by the Cox proportional hazard model.Results: Serum HE4 was significantly associated with CVD history after adjustment for confounding factors (OR= 1.50; 95% CI 1.23– 3.43; P= 0.038) using multivariable logistic regression analysis. The multivariable Cox proportional hazard analysis suggested that serum HE4 had an independent prognostic value for predicting cardiovascular events in patients with breast cancer (HR=2.21, 95% CI 1.60– 5.13, P< 0.001). Additionally, sensitivity analysis showed that the independent association still existed. Stratified analysis showed that this relationship was not affected by chemoradiotherapy.Conclusion: Serum HE4 is significantly related to cardiovascular events and poses good prognostic value for predicting cardiovascular events in obese patients with breast cancer. Serum HE4 may be a valuable indicator for the early detection of cardiovascular complications in obese patients with breast cancer.Keywords: human epididymis protein 4, radiotherapy, breast cancer, cardiovascular events, prognostic value, obese

Contains fulltext : 245825.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

BACKGROUND: This study aimed to compare the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system and the Fuhrman grading system and to verify the WHO/ISUP grade as a prognostic parameter of clear cell renal cell carcinoma (ccRCC) in a Chinese population. METHODS: The study consisted of 753 ccRCC patients treated with curative surgery between 2010 and 2018 at Xiangya Hospital Central South University (Changsha, China). All pathologic data were retrospectively reviewed by two pathologists. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were examined as clinical outcomes. RESULTS: According to the WHO/ISUP grading system (ISUP group), nephrectomy type, pT stage and WHO/ISUP grade were independent risk factors for CSS (P

Rat Thy-1 nephritis (Thy-1N) is an experimental mesangial proliferative glomerulonephritis (MsPGN) for studying human MsPGN. Although sublytic C5b-9 complex formation on glomerular mesangial cells (GMCs) and renal MCP-1 and RANTES production in rats with Thy-1N have been proved, the role and mechanism of MCP-1 or RANTES synthesis in GMCs induced by sublytic C5b-9 are poorly elucidated. In this study, we first found the expression of transcription factor (KLF6), co-activator (KAT7) and chemokines (MCP-1 and RANTES) was all up-regulated both in renal tissue of Thy-1N rats (in vivo) and in sublytic C5b-9-induced GMCs (in vitro). Further in vitro experiments revealed that KLF6 bound to MCP-1 promoter (-297 to -123 nt) and RANTES promoter (-343 to -191 nt), leading to MCP-1 and RANTES gene transcription. Meanwhile, KAT7 also bound to the same region of MCP-1 and RANTES promoter in a KLF6-dependent manner, and KLF6 was acetylated by KAT7 at lysine residue 100, which finally promoted MCP-1 and RANTES expression. Moreover, our in vivo experiments discovered that knockdown of renal KAT7 or KLF6 gene obviously reduced MCP-1 and RANTES production, GMCs proliferation, ECM accumulation, and proteinuria secretion in Thy-1N rats. Collectively, our study indicates that sublytic C5b-9-induced MCP-1 and RANTES synthesis is associated with KAT7-mediated KLF6 acetylation and elevated KLF6 transcriptional activity, which might provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

Background Although 40% to 80% of pediatric patients with pheochromocytoma (PCC) and paraganglioma (PGL) have been reported to carry germline mutations, the genetic and clinical features are poorly understood, and few such patients have undergone genetic testing. In this series, we aimed to investigate the clinical and genetic features of Han Chinese pediatric patients with PCC/PGL. Methods The medical records of 15 pediatric patients with PCC/PGL who presented to our hospital between 2006 and 2018 were retrospectively studied. DNAs isolated from leukocytes of the patients were analyzed using whole-exome sequencing (WES). Results The patients were nine girls and six boys with a mean age of 14.9 (range, 6-18) years. All were alive after a follow-up from 1 to 12 years, although two were diagnosed with pulmonary metastatic PGLs. Four patients were diagnosed with bilateral PCCs. Four patients were diagnosed with tumor syndromes. Among the 15 patients, nine were identified carrying germline mutations, of which seven were VHL and one each of RET and SDHB. In addition, a de novo mutation, VHL c.193T>A, was identified in a patient clinically diagnosed with a VHL syndrome. Conclusions Among 15 pediatric patients studied, nine were identified carrying germline genetic mutations, four were diagnosed with bilateral PCCs, and four were diagnosed with other syndromic tumors in addition to PCC, which underscores the importance of genetic testing and managing treatment accordingly.

OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) plays an important regulatory role in various types of cancers. However, the functional role and regulatory mechanisms of OIP5-AS1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expression of OIP5-AS1 was increased in GC tissues compared with that in adjacent non-cancerous tissues, which was significantly associated with shorter overall survival time of patients. In addition, OIP5-AS1 expression was also increased in GC cell lines including NCI-N87, MKN-45, BGC-823 and SGC-7901, when compared with that in normal gastric epithelial cell line GES-1. Knockdown of OIP5-AS1 markedly suppressed the proliferation and colony formation activities of GC cells, induced G0/G1 arrest and apoptosis of GC cells in vitro, and restrained tumor growth in vivo. Mechanistically, OIP5-AS1 functions as an oncogenic competing endogenous RNA by binding to and sequestering miR-422a to elevate the expression of anoctamin-1. Our study first demonstrated that OIP5-AS1 is a critical and powerful regulator of GC pathogenesis and may represent a novel candidate target for GC therapy.

Purpose Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues relevant to presurgical diagnosis and clinical consequences in patients with a missed presurgical diagnosis of UBPGL. Materials and methods Case reports describing a UBPGL (published from 1–1–2001 and 31–12–2020) were identified in Pubmed. Two authors independently performed data extraction and assessed data quality according to the PRISMA guideline. Patients were divided into two groups: UBPGL diagnosis before and after surgery. Results We included 177 articles reporting 194 cases. In 90 (46.4%) patients, the UBPGL was diagnosed before and in 104 (53.6%) after surgery. In presurgically diagnosed UBPGL, hypertension and catecholamine-associated symptoms were 2- to 3-fold (p p = 0.003) more prevalent in those with postsurgical diagnosis. Hypertension was an independent factor for presurgical biochemical testing (OR 4.45, 95% CI 1.66–11.94) while hematuria (OR 0.23, 95% CI 0.09–0.60) was an independent factor for not performing presurgical biochemical testing. Most patients diagnosed after surgery were not pretreated with alpha-adrenoceptor blockade (95.2%), underwent more frequently transurethral resection instead of cystectomy (70.2% vs. 23.1%) and had more frequent peroperative complications and residual tumor mass. Conclusions In nearly half of all patients with a UBPGL, the diagnosis was not established before surgery. Hypertension and hematuria contributed independently to a presurgical diagnosis. Postsurgical diagnosis, which was associated with suboptimal presurgical and surgical management, resulted in more peroperative complications and incomplete tumor resections.

Pheochromocytoma and paraganglioma (PCC/PGL) are rare tumors that originate from adrenal or extra-adrenal chromaffin cells. A significant clinical manifestation of PCC/PGL is that the tumors release a large number of catecholamines continuously or intermittently, causing persistent or paroxysmal hypertension and multiple organ functions and metabolic disorders. Though majority of the tumors are non-metastatic, about 10% are metastatic tumors. Others even have estimated that the rate of metastasis may be as high as 26%. The disease is most common in individuals ranging from 20 to 50 years old and the age of onset strongly depends on the genetic background: patients with germline mutations in susceptible genes have an earlier presentation. Besides, there are no significant differences in the incidence between men and women. At present, traditional treatments, such as surgical treatment, radionuclide therapy, and chemotherapy are still prior choices. However, they all have several deficiencies so that the effects are not extremely significant. Contemporary studies have shown that hypoxia-associated signal pathway, associated with the cluster 1 genes of PCC/PGL, and increased kinase signal pathways, associated with the cluster 2 genes of PCC/PGL, are the two major pathways involving the molecular pathogenesis of PCC/PGL, indicating that PCC/PGL can be treated with targeted therapies in emerging trends. This article reviews the progress of molecular-targeted therapies for PCC/PGL.

Background: The Von Hippel-Lindau ( VHL ) p.Tyr98His ( Y98H ) mutation is designated as the “Black Forest” founder mutation and has been previously reported in Western countries. This study reports the first recorded Chinese VHL family with the “Black Forest” mutation in Asia. Methods: Paired whole-exome sequencing (WES), Sanger sequencing and immunohistochemistry (IHC) were performed on samples from a large Chinese family to confirm the causative mutation and mutation carriers in the family. Clinical manifestations of the family were summarized and compared with those reported from other patients with the VHL Y98H mutation. Results: The Chinese pheochromocytoma (PCC) family was identified as a VHL type 2 family with a Y98H mutation. There were 4 VHL patients and 11 currently healthy individuals with the mutation. Copy number analysis and SDHB IHC were performed to exclude interference from other pathogenic genes of PCC or paraganglioma (PGL). Conclusions: We report the first recorded instance of a Chinese VHL type 2 family with the “Black Forest” mutation by using WES and Sanger sequencing, which widens the currently recorded presence of the “Black Forest” mutation to China and potentially elsewhere in Asia and indicates that the “Black Forest” mutation does not uniquely evolve in occidental countries. A personalized surveillance approach, which may be more appropriate for affected families, has been recommended to improve quality of life.

Circular RNA_0001313 (circ_0001313), also known as circCCDC66, is a novel circRNA that recently found to be upregulated in colon cancer tissues and promote colon cancer progression. However, the role of circ_0001313 in regulating radio-sensitivity of colon cancer and its molecular mechanism remain undetermined. Here we found circ_0001313 was significantly upregulated and miR-338-3p was downregulated in radio-resistant colon cancer tissues compared to radio-sensitive tissues. Radiation treatment in colon cells triggered a remarkable upregulation of circ_0001313 and a downregulation of miR-338-3p. Knockdown of circ_0001313 reduced cell viability, colony formation rate and increased caspase-3 activity in colon cancer cells under irradiation. Moreover, circ_0001313 act as a sponge for miR-338-3p in colon cancer cells. Furthermore, miR-338-3p could reverse the effects of circ_0001313 knockdown on cell viability, colony formation, and caspase-3 activity. These findings revealed that knockdown of circ_0001313 could induce radio-sensitivity of colon cancer cells by negatively regulating miR-338-3p.

Background To assess the validity and feasibility of the modified hand-assisted retroperitoneoscopic laparoscopic nephrectomy (MHARLN) in patients with benign inflammatory non-functioning kidney diseases. Methods We retrospectively compared the data of 223 patients who underwent an MHARLN (n=142) or an open nephrectomy (ON) (n=81) with benign inflammatory non-functioning diseases between January 2014 and October 2019 at our hospital. Patients' demographic data, perioperative outcomes, preoperative and postoperative inflammatory data, and postoperative complications were reviewed. Results The basic demographic data of patients were similar between the 2 groups. The mean operative times for the MHARLN and the ON were 135 and 143 minutes (P=0.181), respectively. The first time at which postoperative ambulation occurred, the visual analog pain scale (VAS) score before discharge and the postoperative complication rate were similar in both groups. However, compared to the MHARLN, the ON was associated with a more severe inflammatory response on the first day after surgery (P=0.045), higher estimated blood loss (309.8 vs. 139.6 mL; P=0.036), more peritoneal ruptures (19.8% vs. 9.2%; P=0.024), higher intraoperative transfusion (14.82% vs. 4.93%; P=0.011), higher VAS scores 24 hours after surgery (5.9 vs. 5.2; P=0.002), additional analgesic use (35.8% vs. 21.8%; P=0.024), and longer hospital stays (5.3 vs. 4.6 days; P=0.048). Before a liquid diet was commenced in the MHARLN and ON groups, the mean time was 1.2 and 1.5 days, respectively (P=0.004). Conclusions When performed by a skilled laparoscopic surgeon, the use of the MHARLN in patients with benign inflammatory non-functioning kidney diseases is reliable and safe. The MHARLN may help to treat challenging cases and result in less trauma successfully.

Rat Thy-1 nephritis (Thy-1N) is an animal model of human mesangioproliferative glomerulonephritis (MsPGN), accompanied by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition. Although sublytic C5b-9 formed on GMC membrane could induce cell proliferation, the mechanism is still unclear. In this study, we first demonstrated that the level of SRY related HMG-BOX gene 9 (SOX9), general control nonderepressible 5 (GCN5), fibroblast growth factor 1 (FGF1) and platelet-derived growth factor α (PDGFα) was all elevated both in the renal tissues of Thy-1N rats (in vivo) and in the GMCs (in vitro) with sublytic C5b-9 stimulation. Then, we not only discovered that sublytic C5b-9 caused GMC proliferation through increasing SOX9, GCN5, FGF1 and PDGFα expression, but also proved that SOX9 and GCN5 formed a complex and combined with FGF1 and PDGFα promoters, leading to FGF1 and PDGFα gene transcription. More importantly, GCN5 could mediate SOX9 acetylation at lysine 62 (K62) to enhance SOX9 binding to FGF1 or PDGFα promoter and promote FGF1 or PDGFα synthesis and GMC proliferation. Besides, the experiments in vivo also showed that FGF1 and PDGFα expression, GMC proliferation and urinary protein secretion in Thy-1N rats were greatly reduced by silencing renal SOX9, GCN5, FGF1 or PDGFα gene. Furthermore, the renal tissues of MsPGN patients also exhibited positive expression of these genes mentioned above. Collectively, our findings indicate that GCN5, SOX9 and FGF1/PDGFα can form an axis and play an essential role in sublytic C5b-9-triggered GMC proliferation, which might provide a novel insight into the pathogenesis of Thy-1N and MsPGN.

Apelin is an endogenous ligand that binds to the G protein-coupled receptor angiotensin-like-receptor 1 (APJ). Apelin and APJ are widely distributed in organs and tissues and are involved in multiple physiological and pathological processes including cardiovascular regulation, neuroendocrine stress response, energy metabolism, etc. Additionally, apelin/APJ axis was found to play an important role in cancer development and progression. Apela is a newly identified endogenous ligand for APJ. Several studies have revealed the potential role of Apela in cancers. In this article, we review the current studies focusing on the role of apelin/APJ signaling and Apela in different cancers. Potential mechanisms by which apelin/APJ and Apela mediate the regulation of cancer development and progression were also mentioned. The Apelin/APJ signaling and Apela may serve as potential therapeutic candidates for treatment of cancer.

Endocrine neoplasms remain a great threat to human health. It is extremely important to make a clear diagnosis and timely treatment of endocrine tumors. Machine learning includes radiomics, which has long been utilized in clinical cancer research. Radiomics refers to the extraction of valuable information by analyzing a large amount of standard data with high-throughput medical images mainly including computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasound. With the quantitative imaging analysis and model building, radiomics can reflect specific underlying characteristics of a disease that otherwise could not be evaluated visually. More and more promising results of radiomics in oncological practice have been seen in recent years. Radiomics may have the potential to supplement traditional imaging analysis and assist in providing precision medicine for patients. Radiomics had developed rapidly in endocrine neoplasms practice in the past decade. In this review, we would introduce the general workflow of radiomics and summarize the applications and developments of radiomics in endocrine neoplasms in recent years. The limitations of current radiomic research studies and future development directions would also be discussed.

Acute lung injury is characterized by alveolar vascular barrier injury, and protein-rich pulmonary oedema. Alveolar fluid clearance is closely related to the prognosis of patients with acute lung injury. Melatonin has been shown to have a protective effect on multiple organ injury induced by sepsis. In this study we investigated the effect of melatonin on alveolar fluid clearance (AFC) and explored its potential mechanisms in sepsis-induced acute lung injury. The cecal ligation and puncture was adopted to establish mouse sepsis model. Morphological changes of lung tissues with the hematoxylin staining were observed. AFC and lung wet/dry weight ratio were measured to assess pulmonary edema. Inflammatory mediators in bronchoalveolar lavage fluid were analyzed via enzyme-linked immunosorbent assay. NAD+/NADH and SIRT1 activity were measured by colorimetric assay kit. The protein expressions of epithelial sodium channel (ENaC), silent information regulator1 (SIRT1), SGK1 and Nedd4-2 were immunoblotted by western blot in vivo and in vitro. The distribution of α-ENaC and SIRT1 was detected by immunofluorescence. We found that melatonin attenuated sepsis induced lung injury, improved survival rate, enhanced alveolar fluid clearance, improved SIRT1 activity, increased protein expressions of SIRT1 and ENaC, and activated SGK1/Nedd4-2 pathway. Furthermore, SIRT1 inhibitor EX527 counteracted the effects of melatonin on alveolar fluid clearance and ENaC. These results revealed that melatonin enhanced ENaC-mediated AFC via the SIRT1/SGK1/Nedd4-2 signaling pathway. Our study demonstrated that melatonin might provide a novel therapeutic strategy for sepsis-induced acute lung injury.

Background Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a disease with diverse clinical manifestations, such as pelvic pain or perineal pain. Although recent studies found several risk factors related to the pain severity of CP/CPPS patients, results were inconsistent. Here, we aimed to identify novel risk factors that are closely related to the severity of pain in patients with CP/CPPS. Methods We retrospectively collected the clinical records from patients with CP/CPPS from March 2019 to October 2019. The questionnaire was used to obtain related parameters, such as demographics, lifestyle, medical history, etc. To identify potential risk factors related to pain severity, we used the methods of univariate and multivariate logistic regression analyses. Further, to confirm the relationship between these confirmed risk factors and CP/CPPS, we randomly divided CP/CPPS patients into the training and the validation cohorts with a ratio of 7:3. According to the co-efficient result of each risk factor calculated by multivariate logistic regression analysis, a predicting model of pain severity was established. The receiver operating characteristic curve (ROC), discrimination plot, calibration plot, and decision curve analyses (DCA) were used to evaluate the clinical usage of the current model in both the training and validation cohorts. Results A total of 272 eligible patients were enrolled. The univariate and multivariate logistic regression analysis found that age [odds ratio (OR): 2.828, 95% confidence intervals (CI): 1.239–6.648, P = 0.004], holding back urine (OR: 2.413, 95% CI: 1.213–4.915, P = 0.005), anxiety or irritability (OR: 3.511, 95% CI: 2.034–6.186, P P = 0.029), and smoking status (OR: 1.453, 95% CI: 1.313–5.127, P = 0.013) were the risk factors of pain severity. We then established a nomogram model, to test whether these factors could be used to predict the pain severity of CP/CPPS patients in turn. Finally, ROC, DCA, and calibration analyses proved the significance and stability of this nomogram, further confirmed that these factors were closely related to the pain severity of CP/CPPS patients. Conclusions We identify age, holding back urine, anxiety or irritability, contraception, and smoking are risk factors closely related to the pain severity in patients with CP/CPPS. Our results provide novel inspirations for clinicians to design the personalized treatment plan for individual CP/CPPS patient who has suffered different encounters.

Background Evaluation of the feasibility for osteopontin (OPN) to serve as a biomarker in the prognosis and clinical pathological features of prostate cancer patients.Methods The original publications related to osteopontin and prostate cancer were comprehensively searched in the online databases, including PubMed, Embase, Cochrane Library, Web of Science, Medline, Wanfang database and China National Knowledge Infrastructure up to August 2019. Results were analyzed by software Revman 5.3 and Stata 12.0.Results A total of 21 studies were included in the analysis and the result showed that the positive OPN expression group had a lower overall survival than the negative expression group (univariate: HR = 2.32, 95%CI [1.74, 3.10], multivariate: HR = 2.41, 95%CI [1.63, 3.57]) and a lower biochemical relapse-free survival than the negative group (univariate: HR = 1.42, 95%CI [0.92, 2.17], multivariate: HR = 1.61, 95%CI [1.39, 1.87]). In addition, there was a higher expression level of OPN in prostate cancer tissues than in normal prostate tissues (OR = 46.55, 95%CI [12.85, 168.59], p Conclusion Osteopontin could be recognized as a promising novel diagnostic and prognostic biomarker for prostate cancer patients.

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common renal cancer and it has the worst prognosis among all renal cancers. However, traditional radiological characteristics on computed tomography (CT) scans of ccRCC have been insufficient to predict the pathological grade of ccRCC before surgery.MethodsPatients with ccRCC were retrospectively enrolled into this study and were separated into two groups according to the World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system, i.e., low-grade (Grade I and II) group and high-grade (Grade III and IV) group. Traditional CT radiological characteristics such as tumor size, pre- and post-enhancing CT densities were assessed. In addition, radiomic texture analysis based on the CT imaging of the ccRCC were also performed. A CT-based machine learning method combining the traditional radiological characteristics and radiomic features was used in the predictive modeling for differentiating the low-grade from the high-grade ccRCC. Model performance was evaluated with the receiver operating characteristic curve (ROC) analysis.ResultsA total of 264 patients with pathologically confirmed ccRCC were included in this study. In this cohort, 206 patients had the low-grade tumors and 58 had the high-grade tumors. The model built with traditional radiological characteristics achieved an area under the curve (AUC) of 0.9175 (95% CI: 0.8765–0.9585) and 0.8088 (95% CI: 0.7064–0.9113) in differentiating the low-grade from the high-grade ccRCC for the training cohort and the validation cohort respectively. The model built with the radiomic textural features yielded an AUC value of 0.8170 (95% CI: 0.7353–0.8987) and 0.8017 (95% CI: 0.6878–0.9157) for the training cohort and the validation cohort, respectively. The combined model integrating both the traditional radiological characteristics and the radiomic textural features achieved the highest efficacy, with an AUC of 0.9235 (95% CI: 0.8646–0.9824) and an AUC of 0.9099 (95% CI: 0.8324–0.9873) for the training cohort and validation cohort, respectively.ConclusionWe developed a machine learning radiomic model achieving a satisfying performance in differentiating the low-grade from the high-grade ccRCC. Our study presented a potentially useful non-invasive imaging-focused method to predict the pathological grade of renal cancers prior to surgery.

Objective: To analyze the current treatment for low-risk prostate cancer (LRPC) in China. Methods: A national questionnaire survey titled “A survey of current treatment of LRPC” was designed and released nationally through the network from July 16 to August 3, 2017. Results: A total of 1,116 valid questionnaires were recovered. The percentages of preferred treatment by active surveillance (AS) or radical prostatectomy (RP) were 29.21% and 45.61%, respectively. A correspondence analysis showed that the physician in charge was more inclined to choose AS than RP. Respondents from different institution types, hospitals with different annual numbers of newly admitted patients with prostate cancer, and with different familiarity with the LRPC definition presented a significant difference in the preferred treatments (p < 0.05). Urologists chose AS or not for the following reasons: tumor progression (52.51%), potential medical disputes (42.56%) (i.e., medical disputes from patients or their relatives when urologists choose AS to treat patients with LRPC and the patient has a poor outcome), fear of cancer (41.94%), and surgical risk (39.07%). These reasons were ubiquitous, and there was no significant difference among urologists for these concerns (p > 0.05). Personal skills, surgical risk, and tumor progression were the most common factors that influenced whether AS or RP was preferred (p < 0.05). Concern about the medical disputes brought about by AS was a key factor for not choosing AS (p < 0.05). Conclusions: LRPC is still dominated by RP in China, followed by AS. Personal skills, surgical risk, and concern about tumor progression were the common factors influencing whether AS or RP was preferred. In addition, medical disputes brought by AS are another key factor for not choosing AS. There will be more Chinese data in the future to guide treatment of LRPC.

Background: Bladder cancer is one of the most common malignancies in urologic system. The glucocorticoid-inducible kinase 2 (SGK2) expression and function were largely unknown in cancers. Current study was aimed to investigate the role of SGK2 in bladder cancer and its potential mechanisms. Methods: SGK2 expression was quantified by western blot (WB) in multiple bladder cancer cell lines (T24, 5637, J82 and UMUC3) compared with normal urothelial cell line (SVHUC). SGK2 knocking down and overexpression model were established by lentivirus transfection. MTT, colony formation, wound healing and transwell assay were used to assess the tumor cell proliferation, migration and invasion abilities, respectively. In addition, molecular function analysis was performed using FunRich software V3. Immunoprecipitation (IP) assay was applied to investigate the interaction between SGK2 and β-catenin at protein level. TCGA database was retrieved to verify the association between these genes and clinical tumor stage as well as prognosis among bladder cancer patients. Results: SGK2 expression was significantly upregulated in multiple bladder cancer cell lines compared with SVHUC at protein level. Cell proliferation, migration and invasion abilities were significantly decreased after knocking down SGK2 in J82 and UMUC3 cell lines. Inversely, cell aggressive phenotypes were significantly increased after overexpressing SGK2 in T24 cell line. Furthermore, functional analyses of SGK2 based on TCGA database showed that SGK2 related genes were involved in receptor activity, ATP binding, DNA repair protein, trans-membrane receptor activity and lipid binding. In addition, protein interaction analysis identified c-Myc was significantly enriched in SGK2 positively associated genes. The prediction was validated by WB and IP assay that SGK2 could directly bind with β-catenin at protein level to regulate their downstream gene c-Myc expression in bladder cancer to influence tumor progression. And clinical data generated from TCGA database also identified these downstream genes were significantly associated with tumor stage and survival status of bladder cancer patients. Conclusion: Taken together, our findings suggest SGK2 promotes bladder cancer progression via mediating β-catenin/c-Myc signaling pathway, which may serve as a potential therapeutic target for bladder cancer patients.

To retrospectively characterize the clinical, pathological, and computed tomography (CT) findings of renal solitary fibrous tumor/hemangiopericytoma (rSFT/HPC). Twelve patients with rSFT/HPCs were enrolled. The CT findings and clinicopathological features were retrospectively reviewed. This study included six male and six female patients (median age: 47; age range: 20–82 years). Eight benign (grade I) and four malignant (grade III) rSFT/HPCs were identified. Of the 12 lesions, 10 were in the renal sinus near the renal pelvis, while two replaced the whole kidney. Five lesions were well-defined, five were partially ill-defined, and two were ill-defined. Mild (5/12) and intermediate (1/12) hydronephrosis was observed. On the unenhanced CT images, ten tumors showed slightly higher density when compared to the normal renal parenchyma, and two masses were isodense to hypodense. After intravenous contrast medium injection, three enhancement patterns were observed, including “prolonged enhancement” (PE) (6/12), “gradual enhancement” (4/12), and “early washout” (2/12). A central fibrous scar was found in five patients. Compared to the grade I lesions, the grade III rSFT/HPC lesions tended to be larger (maximal diameter > 10 cm) and more heterogeneous with a higher incidence of the PE pattern. We have shown that rSFT/HPCs usually arise from the renal sinus, and present as lobulated, slightly hyperdense, gradually enhancing soft tissue masses. CT findings, including large size, heterogeneity, and the PE pattern, may assist in the pre-operative identification of malignant grade III rSFT/HPCs.

Background/Aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism. Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry. Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription. Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

Objective To retrospectively review the clinicopathologic features and computed tomography (CT) and magnetic resonance imaging (MRI) findings of lumbosacral intraspinal paragangliomas (PGLs). Methods Thirteen patients with surgically and pathologically confirmed lumbosacral intraspinal PGLs were enrolled. Their clinicopathologic data and imaging findings were retrospectively reviewed. Results Ten male and 3 female patients with a median age of 43 years (range, 36–74 years) were included. CT or MRI showed a well-defined (n = 13), oval (n = 10), or striated (n = 3) mass with heterogeneous (n = 6) or homogeneous density/signal intensity (n = 7). The lesions appeared isointense (n = 13) and mildly hyperintense (n = 13) on T1-weighted and T2-weighted MRI, respectively. On enhanced CT/MRI, markedly heterogeneous (n = 6) and homogeneous (n = 7) enhancement patterns were observed. The tadpole sign was observed in 9 cases. Systolic and diastolic blood pressure were higher before than after surgery (PSBP = 0.002 and PDBP = 0.001). Both systolic and diastolic blood pressure were reduced to normal after surgery. No recurrence or metastatic disease was found during the follow-up period. Conclusions Lumbosacral intraspinal PGLs should be considered when a mass appears as well defined or oval, and when a striated solitary homogeneous or heterogeneous mass is characterized by a tadpolelike appearance with a marked enhancement pattern. The fluctuation of blood pressure before and after surgery is an interesting clinical feature of lumbosacral intraspinal PGLs.

Heterozygous germline mutation of the MEN1 tumor suppressor gene is responsible for multiple endocrine neoplasia type 1. Parathyroid and thoracic neuroendocrine tumor specimens and DNA from two Han Chinese MEN1 family patients were analyzed using whole exome and Sanger sequencing. The proband (II-3) was sequentially diagnosed with pituitary adenoma, pancreatic tumor, adrenal cortical tumor, abdominal lipoma, and parathyroid adenoma during the 6-year follow-up. The son of the proband (III-6) was also diagnosed with a thoracic neuroendocrine tumor and a parathyroid adenoma during this period. Splice alterations were studied by RT-PCR and sequencing. The mutation impact was evaluated using bioinformatics. Sequence analysis revealed a novel splice donor mutation, MEN1 IVS9 + 1G > C, that changed the splicing mode of MEN1 to halt translation before two nuclear localization signals in the menin protein. Novel somatic mutations, MEN1 c.1402_1405delGAGG and c.286 C > T, were identified in the parathyroid adenoma of II-3 and thoracic neuroendocrine tumor of III-6, respectively, indicating a two-hit etiology of MEN1 syndrome. Our study revealed the clinical and genetic basis of MEN1 in this Han Chinese family and provides insight into MEN1 mechanisms, diagnosis, and management.

T1 ventral renal hilar tumors (VRHTs) represent a very special type of tumor, for which laparoscopic partial nephrectomy (LPN) by the retroperitoneal approach is challenging. In this study, we report our surgical technique and Trifecta results.Renal rotation technique has been established for retroperitoneal laparoscopic partial nephrectomy (RLPN) for VRHTs in our institution. Trifecta was used as a composite outcome measure for assessing quality of PLPN using this technique. A retrospective analysis of RLPN cases in 12 patients with VRHTs was performed.Mean tumor size was 3.4 cm and median R.E.N.A.L. score was 8 (range 7-9). Mean warm ischemia time was 23.1 minutes, suture time 28.1 minutes, estimated blood loss 139.2 mL, operation time 122.8 minutes, and median hospital stay was 4 days. Three patients (25.0%) had Clavien-Dindo grade I-II complications. Seven patients (58.3%) achieved Trifecta. Postoperative pathological examination showed renal cell carcinoma in all cases with negative surgical margin. A median follow-up of 7 months revealed no local recurrence or distant metastases.Our Trifecta outcomes demonstrate that RLPN with renal rotation technique is feasible, safe, and effective for moderately complex VRHTs. The short-term functional and oncologic outcomes are promising; however, long-term follow-up is needed.

// Zhenyu Ou 1 , Yao He 1 , Lin Qi 1 , Xiongbin Zu 1 , Longxiang Wu 1 , Zhenzhen Cao 2 , Yuan Li 1 , Longfei Liu 1 , Daud Athanasius Dube 3 , Zhi Wang 1 and Long Wang 1 1 Department of Urology, Xiangya Hospital, Central South University, Changsha, China 2 Department of Gynecologic Oncology, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China 3 Department of Urology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe Correspondence to: Long Wang, email: doctorwanglong@163.com Keywords: benign prostatic hyperplasia, mast cell, proliferation, chemokine Received: October 19, 2016 Accepted: June 06, 2017 Published: July 22, 2017 ABSTRACT Early evidences have showed that mast cells could infiltrate into benign prostatic hyperplasia (BPH) tissues, but the exact role of mast cells in BPH development remains unclear. In this study, we identified more mast cells existing in human BPH tissues compared with that in the normal prostate. In the in vitro co-culture system, BPH-1 prostate cells promoted activation and migration of mast cells, and mast cells conversely stimulated BPH-1 cells proliferation significantly. Molecular analysis demonstrated that mast cell-derived interleukin 6 (IL-6) could activate STAT3/Cyclin D1 signals in BPH-1 cells. Blocking IL-6 or STAT3 partially reverse the capacity of mast cells to enhance BPH-1 cell proliferation. Our findings suggest that infiltrating mast cells in BPH tissues could promote BPH development via IL-6/STAT3/Cyclin D1 signals. Therefore, targeting infiltrating mast cells may improve the therapeutic effect of BPH.

Context Pheochromocytomas and paragangliomas (PPGLs) are characterized by distinct genotype-phenotype relationships according to studies largely restricted to Caucasian populations. Objective To assess for possible differences in genetic landscapes and genotype-phenotype relationships of PPGLs in Chinese versus European populations. Design Cross-sectional study. Setting 2 tertiary-care centers in China and 9 in Europe. Participants Patients with pathologically confirmed diagnosis of PPGL, including 719 Chinese and 919 Europeans. Main Outcome Measures Next-generation sequencing performed in tumor specimens with mutations confirmed by Sanger sequencing and tested in peripheral blood if available. Frequencies of mutations were examined according to tumor location and catecholamine biochemical phenotypes. Results Among all patients, higher frequencies of HRAS, FGFR1, and EPAS1 mutations were observed in Chinese than Europeans, whereas the reverse was observed for NF1, VHL, RET, and SDHx. Among patients with apparently sporadic PPGLs, the most frequently mutated genes in Chinese were HRAS (16.5% [13.6-19.3] vs 9.8% [7.6-12.1]) and FGFR1 (9.8% [7.6-12.1] vs 2.2% [1.1-3.3]), whereas among Europeans the most frequently mutated genes were NF1 (15.9% [13.2-18.6] vs 6.6% [4.7-8.5]) and SDHx (10.7% [8.4–13.0] vs 4.2% [2.6–5.7]). Among Europeans, almost all paragangliomas lacked appreciable production of epinephrine and identified gene mutations were largely restricted to those leading to stabilization of hypoxia inducible factors. In contrast, among Chinese there was a larger proportion of epinephrine-producing paragangliomas, mostly due to HRAS and FGFR1 mutations. Conclusions This study establishes Sino-European differences in the genetic landscape and presentation of PPGLs, including ethnic differences in genotype-phenotype relationships indicating a paradigm shift in our understanding of the biology of these tumors.

Background Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). Methods ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients’ clinicopathological features. Results ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. Conclusion Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients’ clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

A new green methodology for the CO2-free synthesis of ammonia from air and water is presented. The conventional production of H2 utilizes fossil fuels and causes a massive greenhouse gas release, making ammonia production one of the most energy intensive and highest CO2 emitting manufacturing processes. In 2014 we introduced an alternative method for efficient ammonia synthesis that utilizes water (along with N2) instead of H2 based on electrolysis of nano-structured catalyst suspensions of Fe2O3 in low temperature aqueous or higher temperature molten hydroxide electrolytes. Here, this is replaced with a solid Fe2O3 catalyst confined to activated charcoal opening pathways to improve the rate and efficiency of ammonia production. Cyclovoltammetric studies show that Fe2O3/AC catalysts can inhibit competing hydrogen reduction and enhance reduction of iron. This iron-based catalyst supported on activated carbon (Fe2O3/AC) was prepared for use as an electrocatalyst for the electrochemical synthesis of ammonia in molten hydroxide (NaOH–KOH) directly from wet N2 at atmospheric pressure. XRD analysis shows that the catalyst exhibits a Fe2O3 structure. At 250 °C, a voltage of 1.55 V with a current density of 49 mA cm−2 yielded the highest rate of ammonia formation, 8.27 × 10−9 mol (s cm2)−1. The highest coulombic efficiency for the 3e− per ammonia formation, 13.7%, was achieved at 1.15 V with a lower average current density of 11 mA cm−2. This is a promising simple technology for the sustainable synthesis of ammonia in the future.

Testicular rupture, one of the most common complications in blunt scrotal trauma, is the rupture of tunica albuginea and extrusion of seminiferous tubules. Testicular rupture is more inclined to young men, and injury mechanisms are associated with sports and motor accidents. After history taking and essential physical examination, scrotal ultrasound is the first-line auxiliary examination. MRI is also one of the vital complementary examinations to evaluate testicular rupture after blunt scrotal trauma. Surgical exploration and repair may be necessary when the diagnosis of testicular rupture is definite or suspicious. Postoperative follow-up is to monitor the relief of local symptoms and changes of testicular functions. This review sums up the literatures about testicular rupture after blunt scrotal trauma in recent 16 years and also refers some new advantages and perspectives on diagnosis and management of testicular rupture.

To evaluate the efficacy and safety of bipolar and monopolar transurethral resection of bladder tumor (TURBT) procedures for non-muscle invasive bladder cancer (NMIBC) patients.We searched for all studies investigating bipolar TURBT and monopolar TURBT for NMIBC patients in PubMed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed. Efficacy was assessed by catheterization time, resection time, pathology, and recurrence rate. Safety was assessed by obturator nerve reflex, bladder perforation, hemoglobin decrease, and transfusion.Our searches identified eight studies. Bipolar TURBT is associated with decreased resection time, catheterization time, and hemoglobin changes. There were no statistically significant differences between bipolar TURBT and monopolar TURBT for rates of obturator nerve reflex, bladder perforation, and transfusion. The grade of cautery artifact had no different between the two procedures or even was lower in the bipolar arm. There was no significant difference in recurrence rate when comparing the two procedures.This systematic review indicates that the bipolar technique is more efficacious and safer for NMIBC patients. More large-scale, multicenter, randomized controlled studies are needed before final clinical recommendations can be made.

The thermal degradation of lignin for value-added fuels and chemicals is important for environment improvement and sustainable development. The impact of pretreatment and catalysis of Ni(NO3)2 on the pyrolysis behavior of organsolv lignin were studied in the present work. Samples were pyrolyzed at 500 ∘C with an upward fixed bed, and the characteristics of bio-oil were determined. After pretreatment by Ni(NO3)2, the yield of monophenols increased from 23.3 wt.% to 30.2 wt.% in &ldquo, Ni-washed&rdquo, and decreased slightly from 23.3 wt.% to 20.3 wt.% in &ldquo, Ni-unwashed&rdquo, Meanwhile, the selective formation of vinyl-monophenols was promoted in &ldquo, which indicated that the existence of nickel species promoted the dehydration of C-OH and breakage of C-C in pyrolysis. In comparison with &ldquo, Water&rdquo, HHV of bio-oil derived from &ldquo, slightly increased from 27.94 mJ/kg to 28.46 mJ/kg, suggesting that the lowering of oxygen content in bio-oil is associated with improved quality. Furthermore, the content of H2 in gas products dramatically increased from 2.0% to 7.6% and 17.1%, respectively.

Objectives To reveal the role of circular RNA (circRNA) DOCK1 (circDOCK1) as a potential biomarker and therapeutic target and its competing endogenous RNA mechanism in bladder carcinoma (BC). Methods The next‐generation sequencing (NGS) technology was introduced to screen the circRNA expression profiles of BC using microarray. qPCR and Western blots assay were employed to measure the gene expression in different groups. Cell counting kit‐8, EdU and transwell assays were applied to detect the cell viability, proliferation and migration potential, respectively. Luciferase reporter assay was used to test the binds between hsa‐miR‐132‐3p/Sox5. Xenografted tumour growth of nude mice was performed to test the role of circDOCK1 in vivo. Results CircDOCK1 was upregulated in BC tissues and cell lines. Repression of circDOCK1 reduced cell viability, inhibited cell proliferation and curbed the cell migration potential of BC cell. CircDOCK1 played its role via regulation of circDOCK1/hsa‐miR‐132‐3p/Sox5 pathway in BC cells. Suppression circDOCK1 inhibited the tumour growth in vivo. Conclusion In this study, we revealed that circDOCK1 affected the progression of BC via modulation of circDOCK1/hsa‐miR‐132‐3p/Sox5 pathway both in vitro and in vivo and providing a potential biomarker and therapeutic targets for BC.

Background/aims: Emerging evidence showed the long noncoding RNA X-inactive specific transcript (lncRNA XIST) may play a crucial role in various cancers. However, its prognostic value in cancer patients remains controversial. Therefore, we performed an in-depth meta-analysis to investigate the potential clinical value of lncRNA XIST as a prognostic marker for cancer patients. Methods: A comprehensive literature search was performed from PubMed, Embase and the Cochrane Central Search Library by January 2018. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% Cl) were calculated to evaluate the prognosis as well as clinicopathological parameters of XIST, respectively. Results: A total of 18 retrospective studies with 1351 cancer patients were included. Current meta-analysis revealed that elevated lncRNA XIST expression was associated with poor overall survival (OS) (HR = 2.14, 95% CI = 1.26–3.64; P = .005) and disease free survival (DFS) (HR = 4.52, 95% CI = 1.42–14.37; P = .011). The clinicopathological parameters analysis demonstrated that increased XIST expression was significantly associated with tumor size (OR = 2.93, 95% CI = 2.24–3.84; P

The basis of learning urology is to master the anatomy of the reproductive system. We can be outstanding surgeons only when clear maps of anatomy are carved in our minds. The aim of this chapter is to elaborate the applied anatomy of the scrotum, testis, epididymis and spermatic cord in the male reproductive system.

Introduction The study was carried out to examine the expression of ataxia telangiectasia mutant (ATM) of clear cell renal cell carcinoma (ccRCC), and to explore the relationship between the expression of ATM and the clinicopathologic parameters and prognosis of ccRCC. Materials and Methods Clinicopathologic data of the patients with ccRCC were collected from January 2011 to August 2015 in Xiangya Hospital, Central South University. The immunohistochemical method was used to detect the expression of ATM in ccRCC and adjacent tissues. The Kaplan-Meier survival method and log-rank test were used to analyze the relationship between ATM expression and the survival time of the patients with ccRCC. Univariate and multivariate Cox regression analysis was used to evaluate the risk factors for the prognosis of ccRCC. Results A total of 110 patients were selected in this study, including 73 men and 37 women. The expression of ATM in ccRCC is significantly lower than that in adjacent tissues. Further analysis found that the expression of ATM in the ccRCC tissues above grade II was lower than that of grade II or below. Kaplan-Meier survival analysis showed that the total survival time of the ATM low expression group was significantly shorter than that of the ATM high expression group. The multivariate Cox regression analysis showed that expression of ATM and clinical stage were independent factors affecting the prognosis of ccRCC. Conclusion ATM expression level could serve as an independent risk factor for the prognosis of ccRCC and could be considered as a potential therapeutic target of ccRCC.

Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.

OBJECTIVES: This study aims to define a radiomic signature for pre-operative differentiation between subclinical pheochromocytoma (sPHEO) and lipid-poor adrenal adenoma (LPA) in adrenal incidentaloma. The goal was to apply a predictive, preventive, and personalized medical approach to the management of adrenal tumors. PATIENTS AND METHODS: This retrospective study consisted of 265 consecutive patients (training cohort, 212 (LPA, 145; sPHEO, 67); validation cohort, 53 (LPA, 36; sPHEO, 17)). Computed tomography (CT) imaging features were evaluated, including long diameter (LD), short diameter (SD), pre-enhanced CT value (CT(pre)), enhanced CT value (CT(post)), shape, homogeneity, necrosis or cystic degeneration (N/C). Radiomic features were extracted and then were used to construct a radiomic signature (Rad-score) and radiomic nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate their performance. RESULTS: Sixteen of three hundred forty candidate features were used to build a radiomic signature. The signature was significantly different between the sPHEO and LPA groups (AUC: training, 0.907; validation, 0.902). The radiomic nomogram based on enhanced CT features (M1) consisted of Rad-score, LD, SD, CT(pre), shape, homogeneity and N/C (AUC: training, 0.957; validation, 0.967). The pre-enhanced CT features based radiomic nomogram (M2) included Rad-score, LD, SD, CT(pre), shape, and homogeneity (AUC: training, 0.955; validation, 0.958). CONCLUSIONS: Our radiomic nomograms based on pre-enhanced and enhanced CT images distinguished sPHEO from LPA. In addition, the promising result using pre-enhanced CT images for predictive diagnostics is important because patients could avoid the additional radiation and risk associated with enhanced CT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-018-0149-3) contains supplementary material, which is available to authorized users.

Objective: Previous studies indicated potential associations between polymorphisms in genes of VEGF/hypoxia/angiogenesis pathway and risk of urogenital carcinomas However, the results were controversial and inconclusive. Here, we conducted an in-depth meta-analysis to investigate the precise associations between polymorphisms in VEGF/hypoxia/angiogenesis related genes and risk of urogenital carcinomas. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane Library to identify all eligible publications. Pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) were calculated to evaluate their associations. Subgroup analysis was conducted to further ascertain such relationship and investigate sources of heterogeneity. Results: In the end, a total of 96 case-control studies fulfilled the inclusion criteria were enrolled for 12 polymorphisms in 4 VEGF/hypoxia/angiogenesis related genes. The pooled results showed eNOS-rs2070744 polymorphism conferred a significantly increased overall risk of urogenital carcinomas in allele, homozygote, and recessive models, respectively. In addition, eNOS-Intron 4a/b VNTR polymorphism was identified related to an increased risk of urogenital carcinomas in recessive model. And VEGF-rs699947 polymorphism was also identified an increased risk of renal cell carcinoma (RCC) in allelic, heterozygote, dominant, homozygote, and recessive models. Conclusion: To conclude, eNOS-rs2070744 and eNOS-Intron 4a/b VNTR polymorphisms are risk factors for urogenital carcinomas. VEGF-rs699947 polymorphism was also identified as an increased risk factor for renal carcinoma.

Objective: To evaluate the feasibility and accuracy of machine learning based texture analysis of unenhanced CT images in differentiating subclinical pheochromocytoma (sPHEO) from lipid-poor adenoma (LPA) in adrenal incidentaloma (AI). Methods: Seventy-nine patients with 80 LPA and 29 patients with 30 sPHEO were included in the study. Texture parameters were derived using imaging software (MaZda). Thirty texture features were selected and LPA was performed for the features selected. The number of positive features was used to predict results. Logistic multiple regression analysis was performed on the 30 texture features, and a predictive equation was created based on the coefficients obtained. Results: LPA yielded a misclassification rate of 19.39% in differentiating sPHEO from LPA. Our predictive model had an accuracy rate of 94.4% (102/108), with a sensitivity of 86.2% (25/29) and a specificity of 97.5% (77/79) for differentiation. When the number of positive features was greater than 8, the accuracy of prediction was 85.2% (92/108), with a sensitivity of 96.6% (28/29) and a specificity of 81% (64/79). Conclusions: Machine learning-based quantitative texture analysis of unenhanced CT may be a reliable quantitative method in differentiating sPHEO from LPA when AI is present.

Resveratrol possesses a wide spectrum of pharmacological properties and has been an ideal alternative drug for the treatment of different cancers, including prostate cancer. However, the mechanisms by which resveratrol inhibits the growth of prostate cancer are still not fully elucidated. To understand the effect of resveratrol on the apoptosis and the epithelial-to-mesenchymal transition (EMT) of prostate cancer as well as its related mechanism, we investigated the potential use of resveratrol in PC-3 prostate cancer cells in vitro using real-time PCR, fluorescence-activated cell sorting, Western blotting, etc. Resveratrol suppresses the PC-3 prostate cancer cell growth and induces apoptosis. Resveratrol also influences the expression of EMT-related proteins (increased E-cadherin and decreased Vimentin expression). Finally, resveratrol also suppressed Akt phosphorylation in PC-3 cells. This study indicates that resveratrol may be a potential anti-cancer treatment for prostate cancer; moreover, it...

We investigated the treatment outcomes of laparoscopic vesicovaginal fistula repair (LVVFR) in patients with supratrigonal vesicovaginal fistula (VVF) in contrast with open transperitoneal vesicovaginal fistula repair (OVVFR).We analyzed 58 VVF repairs from June 2005 to July 2014, with 22 patients in the LVVFR group and 36 in the OVVFR group. Demographic parameters, operative variables, and perioperative outcomes were retrospectively collected and analyzed. The chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test were used for statistical analysis.Patients in both groups had comparable preoperative characteristics. Significantly shorter hospital stay (5.6 vs. 13.2 days, p 0.05) and less blood loss (52 vs. 103 ml, p 0.05) were observed in LVVFR group. Patients in the LVVFR group achieved a higher overall VVF success rate (95.5 % vs. 83.3 %, p 0.05) and recurrent VVF success rate (90.0 % vs. 75.0 %, p 0.05) than OVVFR group, but it was not statistically significant. Patients who underwent OVVFR experienced more postoperative symptomatic bladder spasms (8.3 % vs. 4.5 %, p 0.05), urinary tract infections (UTIs) (5.6 % vs. 0.0 %, p 0.05), and stress urinary incontinence (SUI) (5.6 % vs. 4.5 %, p 0.05), but fewer incidents of postoperative ileus (0.0 % vs. 4.5 %, p 0.05) than the LVVFR group; differences were not significant.Judging from this initial trial, LVVFR should be recommended as the primary intervention to treat supratrigonal VVF patients in view of its reduced blood loss and hospital stay.