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Hsa-miR-599 was identified as a tumor suppressor against cancer. This study aimed to explore possible mechanisms of antitumor effect of hsa-miR-599 against breast cancer. Tissue specimens were collected from 106 breast cancer cases, and breast cancer cell line MCF-7 was cultured for in vitro experiments. The expression pattern of hsa-miR-599 was measured via quantitative real-time polymerase chain reaction. Lipofectamine® 2000 reagent was used for cell transfection. Cell viability, motility and apoptosis were detected using MTT assay, transwell assay, and flow cytometer, respectively. Protein analysis was performed via western blot. Hsa-miR-599 expression was decreased in breast cancer tissues and cells. Moreover, its expression was negatively correlated with TNM stage (p = 0.004) and lymph node metastasis (p = 0.001). Enhanced hsa-miR-599 expression in breast cancer cells could induce the inhibition against cell proliferation, migration and invasion, and strengthen cell apoptosis. BRD4 might be a target of hsa-miR-599. Hsa-miR-599 combined with BRD4 inhibited breast cancer progression through targeting Jagged1/Notch1 pathway. Hsa-miR-599 expression is downregulated in breast cancer. Hsa-miR-599 may inactivate BRD4/Jagged1/Notch1 axis, thus suppressing malignant progression of breast cancer.

Background To investigate osteointegration at the graft-bone interface and the prevention of osteoarthritis after anterior cruciate ligament (ACL) reconstruction using a silk-collagen scaffold with both ends modified by hydroxyapatite (HA) in a rabbit model. Methods The HA/silk-collagen scaffold was fabricated using a degummed, knitted silk scaffold, collagen I matrix, and simulated body fluid (SBF). The HA/silk-collagen scaffold was rolled up to make a graft for replacing the native ACL in the experimental group (HA group), and the silk-collagen scaffold was used in the control (S group). All specimens were harvested at 16 weeks postoperatively to evaluate graft-bone healing and osteoarthritis prevention. Results Histological staining revealed the massive formation of more mature bone at the tendon-bone interface, and immunohistochemistry staining revealed more collagen I and osteocalcin deposition in the HA group than in the S group. Higher signals indicating more bone mineral formation were detected in the HA group than in the S group, which was consistent with the results of biomechanical testing. Better osteoarthritis prevention was also observed in the HA group, indicating a more stable knee joint in the HA group than in the S group. Conclusion The HA/silk-collagen scaffold promotes osteointegration at the tendon-bone interface after ACL reconstruction and has great potential for clinical applications.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a promising imaging modality for detection of biochemical recurrent prostate cancer (BRPCa). This systematic review and meta-analysis was to summarize the impact of PSMA PET on the management of BRPCa patients based on prospective studies. According to the PRISMA statement, articles in Pubmed and Embase were searched till May 26th, 2020 to identify eligible prospective studies that reported changes in the management of BRPCa patients after PSMA PET assessment. The quality of included studies was accessed using the Cochrane Collaboration tool. Meta-analysis was performed using a random-effects model. The pooled change proportion was calculated according to the type of change (just intended vs. implemented). Meta-regression was used to identify significant factors for heterogeneity. Eleven publications involving 1580 patients were included. The pooled proportion of management change in BRPCa patients was 61% (95% CI 55–68%) with significant heterogeneity (p

Background: Mechanism of castration-resistant prostate cancer (CRPC) is still unclear. Our objective is to investigate the association between genes expression and CRPC through the genome-wide approach and functional researches. Methods: Differentially expressed genes (DEGs) between PCa and CRPC tissues were identified using expression profile obtained from Gene Expression Omnibus database (GEO). Survival analysis was performed using online database Gene Expression Profiling Interactive Analysis (GEPIA). Oncomine database was further used to explore the relationship between DEGs expression levels with clinical parameters. After in silico study, SEC14L2-knockdown CRPC cells and normal prostatic epithelial cells were used for in vitro study to verify its biological functions. Results: A total of 3 consistently changed DEGs (SEC14L2, DMD, SEL1L) were identified correlating with CRPC after cross validation in three independent datasets. Low expression of SEC14L2 was associated with poorer disease-free survival and higher Gleason score than normal/high expression of SEC14L2. SEC14L2 knockdown promoted cell proliferation, migration, invasion as well as cell cycle progression in CRPC cells (all P

Robotic adrenalectomy for pheochromocytoma is increasingly popular because of the advantage that have been proved by some researchers recently. However, prospective randomized clinical trials comparing robotic assisted laparoscopic adrenalectomy (RA) with traditional laparoscopic adrenalectomy (LA) for pheochromocytoma are rare. The aim of this study is to compare perioperative outcomes of RA versus LA for pheochromocytoma prospectively.From March 2016 to April 2019, all patients with pheochromocytoma suitable for laparoscopic adrenalectomy were assigned randomly to RA or LA. The primary endpoint was the operative (exclude docking time) time. Secondary endpoints were estimated blood loss and postoperative recovery. Demographics and perioperative data were prospectively collected.A total of 140 (RA 70, LA 70) patients were enrolled in this prospective research. The following significant differences were identified in favor of RA: shorter median operative (exclude docking time) time (92.5 vs 122.5 min, P = 0.007), however, RA group has higher total hospitalization cost (8869.9 vs 4721.8 $, P 0.001). Demographics and other perioperative outcomes were similar in both groups. The RA group showed a significant lower blood loss and operative (exclude docking time) time compared with LA group (P 0.05) for patients with high Nor-Metanephrine (NMN).Both RA and LA for pheochromocytoma are safe and effective. Patients with high NMN can benefit from less blood loss and operative time when a robotic surgery system was used, but RA has a significant higher cost.

The current study was designed to explore the role and underlying mechanism of lncRNA taurine up‐regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin‐eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real‐time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull‐down assay were used to verify the interaction. It is revealed that TUG1 was up‐regulated in the hearts of mice treated by TAC surgery and in PE‐induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR‐34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β‐catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy.

Single-cell RNA sequencing (scRNA-seq) was recently adopted for deciphering intratumoral heterogeneity across cell sub-populations, including clear cell renal cell carcinoma (ccRCC). Here, we characterized the single-cell expression profiling of 121 cell samples and found 44 metastasis-associated marker genes. Accordingly, we trained and validated 17 pivotal metastasis-associated genes (MAGs) in 626 patients incorporating internal and external cohorts to evaluate the model for predicting overall survival (OS) and progression-free survival (PFS). Correlation analysis revealed that the MAGs correlated significantly with several risk clinical characteristics. Moreover, we conducted Cox regression analysis integrating these independent clinical variables into a MAGs nomogram with superior accuracy in predicting progression events. We further revealed the differential landscape of somatic tumor mutation burden (TMB) between two nomogram-score groups and observed that TMB was also a prognostic biomarker; patients with high MAGs-nomogram scores suffered from a higher TMB, potentially leading to worse prognosis. Last, higher MAGs-nomogram scores correlated with the upregulation of oxidative phosphorylation, the Wnt signaling pathway, and MAPK signaling crosstalk in ccRCC. Overall, we constructed the robust MAGs through scRNA-seq and validated the model in a large patient population, which was valuable for prognostic stratification and providing potential targets against metastatic ccRCC.

IntroductionThe clinical performance of [–2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) has been well evaluated in prostate biopsy patients. However, no study has been performed to evaluate the common genetic determinants that affect serum level of p2PSA.Materials and MethodsHere, we performed a two-stage genome-wide association study (GWAS) on the p2PSA level in Chinese men who underwent a transperineal ultrasound-guided prostate biopsy at Huashan Hospital, Shanghai Cancer Center, and Ruijin Hospital in Shanghai, China. Germline variants significantly associated with the p2PSA level in the first stage (n = 886) were replicated in the second stage (n = 1,128). Multivariate linear regression was used to assess the independent contribution of confirmed single nucleotide polymorphisms (SNPs) and known covariates, such as age, to the level of p2PSA.ResultsA novel non-synonymous SNP, rs72725879, in region 8q24.21 of the PRNCR1 gene was significantly associated with the serum level of p2PSA in this two-stage GWAS (p = 2.28 × 10−9). Participants with homozygous “T” alleles at rs72725879 had higher p2PSA levels compared to allele “C” carriers. This variant was also nominally associated with PCa risk (p-combined = 3.44 × 10−18). The association with serum level of p2PSA was still significant after adjusting for PCa risk and age (p = 0.017).ConclusionsOur study shows that the genetic variants in the 8q24.21 region are associated with the serum level of p2PSA in a large-scale Chinese population. By taking inherited variations between individuals into account, the findings of these genetic variants may help improve the performance of p2PSA in predicting prostate cancer.

Activation of the FTO-BRD9 axis confers growth advantage and vulnerability to BRD9 inhibitors in HIF2α low/− clear cell renal cell carcinoma.

Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers. Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly significant environmental risk factor for the occurrence and progress of basal cell carcinoma(BCC). Both cumulative and intermittent high-grade UVR exposure could promote the uncontrolled replication of skin cells. There are also exsiting other contributing environmental factors that combine with the UVR exposure to promote the development of BCC. DNA damage in formation of skin cancers is considered to be a result of UVR toxicity. It is UVR that could activate a series of oncogenes simultaneously inactivating tumor suppressor genes and aberrant proliferation and survival of keratinocytes that repair these damages. Furthermore, mounting evidence demonstrates that inflammatory responses of immune cells in the tumor microenvironment plays crucial role in the skin tumorigenesis as well. In this chapter, we will follow the function of UVR in the onset and development of BCC. We describe the factors that influence BCC induced by UVR, and also review the recent advances of pathogenesis of BCC induced by UVR from the genetic and inflammatory aspects.

Background Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Previous studies suggest that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated. Methods p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S. pneumoniae exposure. At 24 h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal apoptosis and necrosis, inflammation-related transcription factors and proinflammatory cytokines/mediators were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Dynamic changes in inflammation and hippocampal neurogenesis were assessed. Results Our results revealed that both 24 h (acute) and 7, 14, 28 day (long-term) groups of infected rats showed increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS). Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, long-term LM11A-31 treatment accelerated the resolution of PM-induced inflammation and significantly improved hippocampal neurogenesis. Conclusion Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has beneficial effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.

PurposeOur primary aim was to present a combined technique to protect the anatomic integrity of distal urethral sphincter complex (DUSC) during minimally invasive radical prostatectomy (RP) and discuss its impact on urinary continence (UC) recovery. The second aim was to define the learning curve of the combined technique.MethodsWe conducted a non-randomized retrospective study. There were 314 consecutive patients who received RP by the same urologist surgeon with more than 2,000 prior cases in Shanghai Ruijin Hospital between March 2017 and April 2020. Included in this study were 263 patients with clinical T1–T2 stage. We modified a combined RP (Comb-RP) technique including endopelvic fascia no-incising technique, dorsal venous complex (DVC) no-ligation technique, intrafascial dissection technique, and anterior reconstruction technique so as to preserve the anatomic integrity of DUSC. The patients were assigned to two groups: a Comb-RP group and a conventional RP (Conv-RP) group. Continence rates were assessed every 3 months after removal of the catheter. UC was defined as 0 pad per day. Peri-operative variables of the patient including operation time, estimated blood lost (EBL), positive surgical margin (PSM), and postoperative complications were also collected. Scatter-graphs of learning curves were drawn using locally weighted scatterplot smoothing (LOWESS).ResultsRP was accomplished smoothly in all 263 cases. The pad-free UC rates in Conv-RP group and Comb-RP group were 17.3 vs. 27.8% (P = 0.048) at the removal of the catheter, 35.8 vs. 50.0% (P = 0.027) at 1 month, 60.5 vs. 76.1% (P = 0.012) at 3 months, 87.7 vs. 96.5% (P = 0.022) at 6 months, and 94.7 vs. 97.7% (P = 0.343) at 12 months. Kaplan–Meier analysis showed significantly higher and faster continence recovery in the Comb-RP group (mean 4.9 vs. 2.6 months, Log Rank P = 0.001). There was no significant difference in PSM rate between the Comb-RP and Conv-RP group (31.1 vs. 31.2%, P =0.986). The learning curves of peri-operative variables, oncological and functional outcomes achieved the lowest point or plateau at the 20th–60th cases.ConclusionsThe anatomic integrity and intact pelvic floor interplay of DUSC is important for its function. Our combined technique was a safe and feasible technique for improving early UC in RP with no significantly increased PSM rate and no significant difference in long-term UC.

Clear cell renal cell carcinoma (ccRCC) is the main subtype of renal cell carcinoma with varied prognosis. We aimed to identify and assess the possible prognostic long noncoding RNA (lncRNA) biomarkers. LncRNAs expression data and corresponding clinical information of 619 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Differentially expressed genes analysis, univariate Cox regression, the least absolute shrinkage and selection operator Cox regression model were utilized to identify hub lncRNAs. Multivariate Cox regression was used to establish the risk model. Statistical analysis was performed using R 3.5.3. The expression value of five lncRNAs and the risk-score levels were significantly associated with a survival prognosis of ccRCC patients (all P < .001). In the TCGA validation cohort, the area under the curve (AUC) for the integrated nomogram was 0.905 and 0.91 for 3-, 5-year prediction separately. The AUC reached up to 0.757 in an independent ICGC cohort. Besides, the calibration plots also illustrated well curve-fitting between observation values and predictive values. Weighted gene co-expression network analysis and subsequent pathway analysis revealed that the PI3K-Akt-mTOR and hypoxia-inducible factor signaling crosstalk might function as the most essential mechanisms related to the five-lncRNAs signature. Our study suggested that lncRNA AC009654.1, AC092490.2, LINC00524, LINC01234, and LINC01885 were significantly associated with ccRCC prognosis. The prognostic model based on this five lncRNA may predict the overall survival of ccRCC.

Advanced-stage prostate cancer (PCa) is often diagnosed with bone metastasis, for which there are limited therapies. Transforming growth factor β (TGF-β) is known to induce epithelial–mesenchymal transition (EMT), and abundance of TGF-β in the bone matrix is one of the important growth factors contributing to bone metastasis. TGF-β is reported as a key mediator of bone metastasis, but the underlying mechanism has not been elucidated. It was found in our study that Interferon-inducible Transmembrane Protein 3 (IFITM3) played a key role in the regulation of malignant tumor cell proliferation, invasion, and bone migration by binding to Smad4, thus activating the TGF-β-Smads Signaling Pathway. Lentivirus-mediated short hairpin RNA (shRNA) knockdown of IFITM3 inhibited cell proliferation and colony formation, induced apoptosis and inhibited migration by reversing EMT and downregulating the expression of metastasis-related molecules including FGFs and PTHrP. Microarray analysis showed that IFITM3 knockdown could alter the MAPK pathway associated with TGF-β-Smads signaling. By knocking down and overexpressing IFITM3, we demonstrated that IFITM3 expression level had an effect on MAPK pathway activation, and this change was more pronounced upon exogenous TGF-β stimulation. These results suggest that IFITM3 played an oncogenic role in PCa progression and bone metastasis via a novel TGF-β-Smads-MAPK pathway.

Adrenal pheochromocytoma (PCC) is a very rare tumor that stems from chromaffin cells, which can develop into malignant tumor. During the operation, abundant blood vessels were often observed in PCC than other adrenal tumors, which increases the difficulty and risk of the surgery. Therefore, it is important to investigate the mechanism of PCC angiogenesis. Twelve surgical specimens of PCC from Ruijin Hospital, Shanghai Jiaotong University were grouped into high and low microvessel density (MVD) group. They were also divided into rich blood supply and nonenriched blood supply group, according to computed tomography (CT) manifestation. Comparative proteomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis revealed that 206 proteins differentially regulated in the high MVD group compared with low MVD group (p < 0.05). Besides, 61 proteins were discovered to be significantly changed when the 12 samples were grouped according to CT manifestation. By intersecting the differentially changed protein from MVD and CT grouping, 25 proteins were filtered out, with pathological function. COX4I2 was verified to be increased gradually with angiogenesis with increasing severity, and PLAT was shown to be decreased with angiogenesis in PCC, by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. The quantitative proteomics result indicated that the tumor angiogenesis in PCC is associated with hypoxia. COX4I2 and PLAT were highly correlated with blood supply in PCC which contribute to angiogenesis in PCC, which could be used as biomarkers to better indicate tumor angiogenesis, or targets to regress tumor angiogenesis as treatment.

BACKGROUND Adrenal primitive neuroectodermal tumor (PNET) is an extremely rare malignant tumor with poor prognosis and of neural crest origin. Herein, we report a case of adrenal PNET and summarized its clinical and pathological characteristics on the basis of 16 patients reported recently. CASE SUMMARY A female patient aged 25 years presented with right lumbago for 12 mo, and pre-operative computed tomography showed a huge right adrenal mass. She received tumorectomy, and post-operative pathological examination showed adrenal PNET. After surgery, she underwent adjuvant chemotherapy and was followed up 31 mo after surgery. She received brachytherapy for right paracolic and hepatic metastases. She was alive and followed up for 60 mo. In available studies, only 57.14% (4/7) and 44.44% (4/9) were positive for the expression of neuron-specific enolase and synaptophysin, respectively, although CD99 expression was found in all the patients (100%; 10/10). CONCLUSION It is concluded that adrenal PNET is very rare and highly malignant, and histology is a golden standard in its diagnosis. Surgery and adjuvant therapy is the main treatment.

Cryptococcus gattii (C. gattii) is a lethal pathogen that causes the majority of cryptococcosis cases in previously healthy individuals. This pathogen poses an increasing threat to global public health, but the mechanisms underlying the pathogenesis have remained to be fully elucidated. In the present study, the role of high-osmolarity glycerol (HOG)1 in the stress reaction and virulence control of C. gattii was characterized by deleting the HOG1 gene using the clinical isolate strain CZ2012, and finally, the virulence and pathogenic traits of the deletion strain were defined. Deletion of the HOG1 gene resulted in notable growth defects under stress conditions (high salt and antifungal drugs), but different traits were observed under oxidative stress conditions (hydrogen peroxide). Similarly, the C. gattii hog1Δ strains (deletion of HOG1) also displayed decreased capsule production and melanin synthesis. Furthermore, mice infected with the hog1Δ strain had longer survival times than those infected with the wild-type strain and the reconstituted strain. The hog1Δ strain recovered from infected organs exhibited significant growth defects in terms of decreased colony count and size. The present results suggested that HOG1 has a significant role in the virulence of C. gattii and these results may help to elucidate the pathogenesis of C. gattii.

ObjectiveThe aim of this study is to investigate the biological functions and the underlying mechanisms of DNA polymerase epsilon subunit 2 (POLE2) in renal cell carcinoma (RCC).MethodsThe datasets of POLE2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases was selected and the correlation between POLE2 and various clinicopathological parameters was analyzed. The POLE2 expression in RCC tissues was examined by immunohistochemistry. The POLE2 knockdown cell lines were constructed. In vitro and in vivo experiments were carried out to investigate the function of POLE2 on cellular biology of RCC, including cell viability assay, clone formation assay, flow cytometry, wound-healing assay, Transwell assay, qRT-PCR, Western blot, etc. Besides, microarray, co-immunoprecipitation, rescue experiment, and Western blot were used to investigate the molecular mechanisms underlying the functions of POLE2.ResultsPOLE2 was overexpressed in RCC tissues, and high expression of POLE2 was correlated with poor prognosis of RCC. Furthermore, knockdown of POLE2 significantly inhibited cell proliferation, migration, and facilitated apoptosis in vitro. In vivo experiments revealed that POLE2 attenuated RCC tumorigenesis and tumor growth. we also illuminated that stanniocalcin 1 (STC1) was a downstream gene of POLE2, which promoted the occurrence and development of RCC. Besides, knockdown of POLE2 significantly upregulated the expression levels of Bad and p21 while the expression levels of HSP70, IGF-I, IGF-II, survivin, and sTNF-R1 were significantly downregulated. Western blot analysis also showed that knockdown of POLE2 inhibited the expression levels of Cancer-related pathway proteins including p-Akt, CCND1, MAPK9, and PIK3CA.ConclusionKnockdown of POLE2 attenuates RCC cells proliferation and migration by regulating STC1, suggesting that POLE2-STC1 may become a potential target for RCC therapy.

Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high‐throughput sequencing data revealed that JMJD6 could assemble super‐enhancers to drive a list of identity genes in kidney cancer, including VEGFA, β‐catenin, and SRC. Moreover, this JMJD6‐mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient‐derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients., The CRISPR/Cas9 functional screening data and multiple RCC datasets were used to identify JMJD6 as the epigenetic vulnerability in RCC. Accumulated JMJD6 mainly constitutes super‐enhancers to alter oncogenic crosstalk and targeting JMJD6 was an effective approach to suppress RCC progression.

PurposeThis study aimed to evaluate the clinical utility of 18F-PSMA-1007 positron emission tomography (PSMA PET)/magnetic resonance imaging (MRI) imaging in patients with suspected or defined prostate cancer.MethodsIn the pilot study, we retrospectively investigated 62 patients who underwent PSMA-PET/MRI for suspected or defined PCa between June 2019 and June 2020. Patients were grouped into three subgroups: (1) suspected PCa without histological evidence, (2) primary PCa, (3) biochemical recurrent prostate cancer (BRPCa). Two nuclear physicians independently interpreted the results of PSMA-PET/MRI. Management strategies before PSMA-PET/MRI were retrospectively reported, and the management strategy was re-evaluated for each patient considering the PSMA-PET/MRI result. The changes in strategies were recorded. Besides, the correlation between prostate specific antigen (PSA) level and management changes was also accessed by Fisher exact test, and two-side p < 0.05 was assumed as statistical significance.ResultsThere were 28 patients in the suspected PCa group (group 1), 12 in the primary PCa group (group 2), and 22 in the BRPCa group (group 3). Overall, the intended decisions were changed in 26 (41.9%) of 62 patients after PSMA-PET/MRI, including 11/28 (39.3%) in suspected PCa group, 1/12 (8.4%) in primary PCa group, and 14/24 (63.6%) in BCR group. In group 1, the main impact on subsequent management included decreased active surveillance (from 20 to 9) and increased prostate biopsy (from 8 to 19). PSA levels were not significantly associated with management changes in suspected PCa patients (p = 0.865). In group 2, the main impact on subsequent management included decreased radical surgery (from 8 to 7), and multimodal therapy appearance (n = 1). Only in the category of PSA levels of ≥20 ng/ml, the management of primary PCa was changed. In group 3, the main impact on subsequent management included decreased salvage radiotherapy (from 5 to 2), increased systemic therapy (from 6 to 7), and increased multimodal therapy (from 11 to 13). The highest proportion of management changes occurred in BCR patients with 0.5≤PSAConclusionFrom our preliminary experience, PSMA-PET/MRI may be a valued tool for defining PCa lesions and changing management. The biggest impact of management intent was in patients with BRPCa, especially in patients with 0.5≤PSA

Background Prostate health index (phi), a derivative of [−2]proPSA (p2PSA), has shown better accuracy than prostate‐specific antigen (PSA) in prostate cancer (PCa) detection. The present study was to investigate whether previously identified PSA‐associated single nucleotide polymorphisms (SNPs) influence p2PSA or phi levels and lead to potential clinical utility. Methods We conducted an observational prospective study with 2268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ± 100 kb window were tested for association with p2PSA and phi levels using linear regression. Multivariable logistic regression models were performed and internally validated using repeated tenfold cross‐validation. We further calculated personalized phi cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index. Results We detected 11 significant variants at 19q13.33 which were p2PSA‐associated independent of PCa. The most significant SNP, rs198978 in KLK2 (P combined = 5.73 × 10−9), was also associated with phi values (P combined = 3.20 × 10−6). Compared to the two commonly used phi cutoffs of 27.0 and 36.0, the personalized phi cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p

BackgroundClinical studies have suggested that prostate health index (phi) outperforms prostate-specific antigen (PSA) tests in prostate cancer detection. The cost-effectiveness of phi with different cutoffs is poorly understood in the context of decision making for prostate biopsy.MethodsIn a multicenter cohort, 3,348 men with elevated total PSA (tPSA) underwent initial prostate biopsy from August 2013 to May 2019. We constructed a decision model to evaluate the incremental cost-effectiveness ratios of different phi cutoffs. Total costs and reimbursement payments were based on the fee schedule of Shanghai Basic Medical Insurance and converted into United States dollars ($). Two willingness-to-pay thresholds were estimated as one or three times the average gross domestic product per capita of China ($7,760 or $23,279, respectively).ResultsThe total costs of prostate biopsy and PSA tests were estimated at $315 and $19, respectively. The cost of phi test varied between $72 to $130 in different medical centers. Under different phi cutoffs (from 23 to 35), phi test predicted reductions of 420 (21.7%) to 972 (50.2%) in unnecessary biopsies, with a total gain of 23.77–57.58 quality adjusted life-years compared to PSA tests. All the cutoffs would be cost-effective for patients with tPSA levels of 2–10 ng/ml. Applying 27 as the cutoff was cost-effective for each tPSA range, with missing positive cases ranging from 11 (3.4%) to 33 (11.5%).ConclusionsUsing phi test was cost-effective in the decision-making process for initial prostate biopsy, especially for patients with tPSA values between 2–10 ng/ml. The phi cutoff of 27 was cost-effective regardless of tPSA ranges and should be recommended from a health-economic perspective.

Psoriasis is a common chronic, immune-mediated, inflammatory skin disorder, with a reported prevalence of 0.0-2.1% among children and 0.91-8.50% among adults, worldwide. Psoriasis is induced by several environmental factors, including infection, alcohol consumption, drugs, trauma, acute withdrawal of systemic or potent topical corticosteroids, body mass index and endocrine disorders. Increasing evidence suggest that a variety of microorganisms play key roles in the induction and exacerbation of psoriasis. Pathogens, such as streptococci and staphylococci are considered causal factors, presumably via superantigen activation of skin-seeking T cells. In addition, fungal pathogens, such as Candida and Malassezia, and viral agents, such as human immunodeficiency virus, hepatitis C virus infection and human papillomavirus, are also closely associated with psoriasis. Recently, several types of pathogens, such as Helicobacter pylori infection, Zika virus and scabies, have been reported to potentially trigger psoriasis. The present review discusses the underlying molecular mechanisms by which these infections influence psoriasis to provide a better understanding of the pathogenesis of psoriasis.

Prostate cancer stemness (PCS) cells have been reported to drive tumor progression, recurrence and drug resistance. However, there is lacking systematical assessment of stemlike indices and associations with immunological properties in prostate adenocarcinoma (PRAD). We thus collected 7 PRAD cohorts with 1465 men and calculated the stemlike indices for each sample using one-class logistic regression machine learning algorithm. We selected the mRNAsi to quantify the stemlike indices that correlated significantly with prognosis and accordingly identified 21 PCS-related CpG loci and 13 pivotal signature. The 13-gene based PCS model possessed high predictive significance for progression-free survival (PFS) that was trained and validated in 7 independent cohorts. Meanwhile, we conducted consensus clustering and classified the total cohorts into 5 PCS clusters with distinct outcomes. Samples in PCScluster5 possessed the highest stemness fractions and suffered from the worst prognosis. Additionally, we implemented the CIBERSORT algorithm to infer the differential abundance across 5 PCS clusters. The activated immune cells (CD8+ T cell and dendritic cells) infiltrated significantly less in PCScluster5 than other clusters, supporting the negative regulations between stemlike indices and anticancer immunity. High mRNAsi was also found to be associated with up-regulation of immunosuppressive checkpoints, like PDL1. Lastly, we used the Connectivity Map (CMap) resource to screen potential compounds for targeting PRAD stemness, including the top hits of cell cycle inhibitor and FOXM1 inhibitor. Taken together, our study comprehensively evaluated the PRAD stemlike indices based on large cohorts and established a 13-gene based classifier for predicting prognosis or potential strategies for stemness treatment.

Streptococcus pneumoniae meningitis is a life-threatening bacterial infection of the central nervous system (CNS), and its unfavorable prognosis usually results from an intense inflammatory response. Recent studies have shown that brain-derived neurotrophic factor (BDNF) mediates anti-inflammatory and neuroprotective effects in CNS diseases; however, the distinct contribution of BDNF to pneumococcal meningitis (PM) remains unknown. In this study, we sought to investigate the effects of endogenous BDNF on the inflammatory response and brain damage in experimental PM. We used Camk2a-CreERT2 mice to delete Bdnf from the cerebral cortex and hippocampus, and meningitis was induced by intracisternal infection with S. pneumoniae. Clinical parameters were assessed during acute meningitis. At 24 h post-infection, histopathology, neutrophil granulocytes infiltration, and microglia/macrophage proliferation of brain tissues were evaluated. Additionally, cortical damage and hippocampal apoptosis were assessed using Nissl staining and terminal deoxynucleotidyl transferase dUTP-nick-end labeling (TUNEL), respectively. Pro-inflammatory cytokine levels were determined using real-time polymerase chain reaction (RT-PCR). Key molecules associated with the related signaling pathways were analyzed by RT-PCR and western blot. To investigate the role of microglia/macrophage in infected BDNF conditional knockout mice, GW2580 was used for microglia/macrophage depletion. Here, we, for the first time, found that BDNF conditional knockouts exhibited more profound clinical impairment, pathological severity, and neuron injury and enhanced microglia/macrophage proliferation than were observed in their littermate controls. Furthermore, the BDNF conditional knockouts showed an obviously increase in the expression of pro-inflammatory factors (Tnf-α, Il-1β, and Il-6). Mechanistically, loss of BDNF activated TLR2- and NOD2-mediated downstream nuclear factor kappa B (NF-κB) p65 and p38 mitogen-activated protein kinase (MAPK) pathways associated with S. pneumoniae infection. Furthermore, targeted depletion of microglia/macrophage population decreased the resistance of mice to PM with diminishing neuroinflammation in BDNF conditional knockouts. Our findings suggest that loss of BDNF may enhance the inflammatory response and contribute to brain injury during PM at least partially by modulating TLR2- and NOD2-mediated signaling pathways, thereby providing a potential therapeutic target for future interventions in bacterial meningitis pathologies.

Objective To evaluate the impact of an enhanced recovery after surgery (ERAS) pathway on patients undergoing minimally invasive radical prostatectomy at a single institute. Methods In this retrospective study, 301 patients who underwent laparoscopic or robot-assisted laparoscopic radical prostatectomy from May 2014 to September 2018 were consecutively recruited. Before April 2017, the patients were treated with conventional care; all patients were treated with the ERAS pathway thereafter. The primary outcome was the postoperative length of hospital stay (LOS). The secondary outcomes were hospitalization costs and postoperative complications. Results In total, 138 patients were treated with the ERAS pathway, and the remaining patients underwent conventional care. The postoperative LOS was significantly shorter in the ERAS group than in the conventional group (median, 6 vs. 8 days). The hospitalization costs were also significantly lower in the ERAS group ($4086 vs. $5530). Ten (6.1%) patients in the ERAS group and 17 (12.3%) patients in the conventional group developed postoperative complications. The multivariable analysis showed that ERAS care was a significant independent predictive factor for a shortened LOS and reduced hospitalization costs. Conclusions The ERAS pathway was associated with a shortened LOS and reduced hospitalization costs for patients undergoing minimally invasive radical prostatectomy.

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤ 2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥ 3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG ≥ 2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

Jian-Min Lv,1–3,* Lu Chen,1,* Yi Gao,1,* Hai Huang,1–3,* Xiu-Wu Pan,2,3,* Xi Liu,1 Ming Chen,2 Fa-Jun Qu,3 Lin Li,3 Jun-Kai Wang,2 Xin-Gang Cui,3,4,* Dan-Feng Xu1,* 1Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; 2Department of Urinary Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 3Department of Urinary Surgery, Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, China; 4Department of Urinary Surgery, Gongli Hospital, Second Military Medical University, Shanghai 200135, China *These authors contributed equally to this work Background: Prostate cancer (PCa) is one of the most common malignancies and a major leading cause of cancer-related deaths in males. And it is necessary to explore new molecular targets to enhance diagnosis and treatment level of the PCa. Serine/threonine protein phosphatase 5 (PPP5C) is a vital molecule that Involve in complex cell physiological activity. Purpose: The objective of this study was to detecte the expression level of PPP5C in the tissue of prostate cancer patients and further discussed the PPP5C biological function and mechanisms on the PCa. Methods: The expression level of PPP5C was analyzed by immunohistochemistry and ONCOMINE datasets. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of PPP5C in prostate cancer cell. Cell viability and proliferation were measured using MTT and colony formation, and the cell cycle and apoptosis was analyszed by flow cytometry. The changes of downstream protein level and protein phosphorylation level were detected by western blot. Results: PPP5C was highly expressed in PCa tissue as analyzed by immunohistochemistry and ONCOMINE datasets. PPP5C Knockdown inhibited cell proliferation and colony formation in PCa cells. Flow cytometry analysis showed that DU145, PC3 and 22RV1 PCa cells deprived of PPP5C were arrested in G0/G1 phase and became apoptotic. Western blot analysis indicated that PPP5C knockdown could promote JNK and ERK phosphorylation. Conclusion: Our study indicated that the PPP5C may become a new potential diagnostic biomarker and therapeutic target for the PCa. Keywords: PPP5C, prostate cancer, tumorigenesis, JNK, ERK

The goal of this research was to study the relationships between maternally expressed gene 3 (MEG3), microRNA-7 (miR-7), and RASL11B, and explore their influence on the progression of clear cell renal cell carcinoma (CCRCC). Microarray analysis was conducted using the data provided by The Cancer Genome Atlas. The expression levels of MEG3 and miR-7 in CCRCC and adjacent tissue samples were ascertained by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation activity was unmasked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell apoptosis and cell cycle were investigated by flow cytometry. A dual luciferase reporter assay was used to verify target relationships. Wound healing assay and transwell assay were used to detect cell migration and invasion ability. Decreased MEG3 expression was observed in CCRCC tissues and cells. Overexpression of MEG3 accelerated apoptosis; inhibited cell proliferation, migration and invasion; and induced G0/G1 phase cell cycle arrest in CCRCC. MiR-7, directly binding to MEG3, was overexpressed in the CCRCC tissues and could inhibit the apoptosis and promote the migration and invasion of CCRCC cells. RASL11B, lowly expressed in CCRCC, was a target of miR-7. After the overexpression of RASL11B, G0/G1 phase cell cycle arrest was induced; cell apoptosis was promoted; and the proliferation, invasion, and migration of CCRCC cells were inhibited. MEG3 could up-regulate RASL11B to inhibit the cell proliferation, invasion, and migration; induce G0/G1 cell cycle arrest; and promote cell apoptosis by suppressing miR-7 in CCRCC.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p

Background Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. Objective To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. Design, setting, and participants The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. Outcome measurements and statistical analysis The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses. Results and limitations We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated. Conclusions There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression. Patient summary We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.

// Juping Zhao 1, * , Jun Dai 1, * , Wenlong Zhou 1 , Haofei Wang 1 , Wenbin Rui 1 , Wei He 1 , Zhe Zhu 2, 3 , Yu Zhu 1 , Danfeng Xu 1 and Fukang Sun 1 1 Shanghai JiaoTong University School of Medicine, Ruijin Hospital, Department of Urology, Shanghai, 200025 China 2 Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, 92037 USA 3 Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195 USA * These authors contributed equally to this work Correspondence to: Fukang Sun, email: sfk10570@rjh.com.cn Keywords: aldosterone-producing adenoma, predictor, hypertension urgency, laparoscopic adrenalectomy Received: July 04, 2017 Accepted: September 21, 2017 Published: October 07, 2017 ABSTRACT Study about blood pressure variation in the first 24 hours post-operation is limited in patients with adrenal aldosterone-producing adenoma. We aim to evaluate the potential predictors for postoperative hypertension urgency during the first 24 hours after laparoscopic adrenalectomy in patients with aldosterone-producing adenoma. Clinical data of 177 patients with aldosterone-producing adenoma were retrospectively collected from January 2009 to December 2015 and the potential factors that may influence postoperative blood pressure during the first 24 hours after surgery were analyzed. The factors included gender, age, body mass index, preoperative maximum systolic blood pressure, number of antihypertensive medicines, preoperative spironolactone treatment, duration of hypertension, surgical method and approach, adenoma diameter, preoperative proteinuria, estimated glomerular filtration rate, serum potassium and serum aldosterone. Univariate and multivariate regression analyses were used to evaluate the relationship between the above variables and postoperative hypertension urgency. We found that the proportion of patients with a higher systolic blood pressure ≥ 160 mmHg and ≥ 180 mmHg were significantly increased post-operation (both p < 0.001). In multivariate analysis, the maximum systolic blood pressure was an independent predictor of postoperative hypertension urgency, and the cut-off point was 157 mmHg with the sensitivity of 66% and specificity of 82%. Multivariable analysis also showed that preoperative maximum systolic blood pressure and number of antihypertensive medicines were independent risk factors for higher postoperative systolic blood pressure. This study was derived from a high volume adrenal tumor center, and these data may provide a potential tool to guide preoperative counseling.

// Xi Liu 1, 3, * , Lu Chen 1, * , Hai Huang 1, 3, * , Jian-Min Lv 1, * , Ming Chen 3 , Fa-Jun Qu 2 , Xiu-Wu Pan 2 , Lin Li 2 , Lei Yin 3 , Xin-Gang Cui 2 , Yi Gao 1 and Dan-Feng Xu 1 1 Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China 2 Department of Urinary Surgery, Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, China 3 Department of Urinary Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China * These authors have contributed equally to this work Correspondence to: Xin-Gang Cui, email: xingangcui@126.com Yi Gao, email: gaoyismmu@163.com Dan-Feng Xu, email: danfengxu_urology@163.com Keywords: PDLIM5; epithelial-mesenchymal transition; prostate cancer; migration; AMPK Received: July 13, 2017 Accepted: August 27, 2017 Published: September 18, 2017 ABSTRACT PDZ and LIM domain 5 (PDLIM5) is a cytoskeleton-associated protein and has been shown to bind to a variety of proteins through its specific domain, thereby acting to regulate cell migration and tumor progression. Here, we found that PDLIM5 was abnormally upregulated in prostate cancer (PCa) tissues as compared with that in normal prostate tissue. ONCOMINE microarray data mining showed that PDLIM5 was closely correlated with the prognosis of PCa in terms of Gleason score, tumor metastasis and biochemical recurrence. Lentivirus-mediated short hairpin RNA (shRNA) knockdown of PDLIM5 inhibited cell proliferation and colony formation, arrested hormone independent PCa cells DU145 and PC-3 in G2/M phase, and induced apoptosis. Meanwhile, silencing PDLIM5 inhibited migration and invasion of tumor cells by reversing the mesenchymal phenotype and a similar result was confirmed in a xenograft nude mouse model. Finally, we found PDLIM5 plays a crucial role in regulating malignant tumor cell proliferation, invasion and migration by binding to AMPK and affecting its activation and degradation, and may therefore prove to be a potential oncogenic gene in the development and progression of PCa.

Prostate cancer is one of the leading causes of cancer death for male. In the present study, we applied an integrated bioinformatics approach to provide a novel perspective and identified some hub genes of prostate cancer. Microarray data of fifty-nine prostate cancer were downloaded from Gene Expression Omnibus. Gene Ontology and pathway analysis were applied for differentially expressed genes between high and low grade prostate cancer. Weighted gene coexpression network analysis was applied to construct gene network and classify genes into different modules. The most related module to high grade prostate cancer was identified and hub genes in the module were revealed. Ingenuity pathway analysis was applied to check the chosen module’s relationship to high grade prostate cancer. Hub gene’s expression profile was verified with clinical samples and a dataset from The Cancer Genome Atlas project. 3193 differentially expressed genes were filtered and gene ontology and pathway analysis revealed some cancer- and sex hormone-related results. Weighted gene coexpression network was constructed and genes were classified into six modules. The red module was selected and ingenuity pathway analysis confirmed its relationship with high grade prostate cancer. Hub genes were identified and their expression profile was also confirmed. The present study applied integrate bioinformatics approaches to generate a holistic view of high grade prostate cancer and identified hub genes could serve as prognosis markers and potential treatment targets.

Background Use biomechanical technique to access the strain distribution and stability of Contour anti-protrusion cage with or without the whole circumference acetabular cup fixation by the transacetabular screws. Methods Pelvic specimens from 10 male cadavers were used for the biomechanical test. The models of type C bone defect were copied according to the AAOS classification. Group 1: the contour reconstruction ring was fixed only by flange screws; Group 2: the contour reconstruction ring was fixed both by flange screws and transacetabular screws in dome. Under load in Heel Strike, Midstance, and Toe off phase, the transverse and longitudinal strains were measured in both the superior measure site near the root of the iliac wing and the inferior measure site near the root of the ischium. The relative displacement between the anterior inferior spine and the root of ischium below acetabular component was also measured. Findings Compared with Group 1, the transverse and longitudinal pressure strain of Group 2 on the superior measure site decreased, and measure sites also showed reductions on the inferior under load under three different gait phases. The result of mean relative displacement showed transacetabular screws fixation couldn't provide significant improvement of displacement prevention. Interpretation Biomechanical test showed that under the premise of a satisfied bone allograft and well-fixed flange screws in iliac and ischium, the satisfactory initial stability of the reconstruction cup can be achieved, but could not be improved by transacetabular screw technique. However, the max strain in root part of the flange will be reduced using transacetabular screws in ilium, pubis and ischium together, and the strain distribution will also be improved.

Serine/threonine protein phosphatase 5 (PPP5C) is a member of the protein serine/threonine phosphatase family and has been shown to participate in multiple signaling cascades and tumor progression. We found that PPP5C was highly expressed in bladder cancer tissues compared to normal urothelial tissues, and positively correlated to tumor stages through ONCOMINE microarray data mining. Knockdown of PPP5C via a lentivirus-mediated short hairpin RNA (shRNA) markedly inhibited cell proliferation and colony formation. Flow cytometric analysis showed that PPP5C-deficient T24 and BT5637 bladder cancer cells were arrested in G0/G1 phase and induced apoptosis. In addition, tumor growth was inhibited in vivo in a xenograft nude mouse model. Further studies indicated that knockdown of PPP5C downregulated c-myc and CDK4, whereas upregulated p27, BAD and Beclin1. These results suggest that PPP5C is associated with bladder cancer (BCa) and plays an oncogenic role in the development and progression of bladder cancer.

To conduct a systematic review and Meta-analysis of the literature on the efficacy and safety of B-TURP versus HoLEP for the treatment of benign prostatic hyperplasia (BPH) in terms of demographic and clinical baseline characteristics, peri-operative variables, and postoperative outcomes and complications.Trials comparing B-TURP and HoLEP were identified systematically using Pubmed, Embase, CNKI, Web of Science and the Cochrane Library. Primary outcomes were the peak urinary flow rate (QFour trials assessing B-TURP and HoLEP were considered eligible for Meta-analysis, including three randomized controlled trials (RCTs) and one retrospective study. There was no statistically significant difference between B-TURP and HoLEP in terms of QBoth B-TURP and HoLEP are safe and minimally invasive techniques that are similar in terms of symptomatic relief, although these findings need further validation in larger RCTs involving larger numbers of patients and over a longer follow-up duration for B-TURP or HoLEP before a new gold standard procedure emerges for surgical treatment of BPH.

// Lu Chen 1, * , Xiu-Wu Pan 2, 3, * , Hai Huang 3, * , Yi Gao 3 , Qi-Wei Yang 2, 3 , Lin-Hui Wang 3 , Xin-Gang Cui 2 and Dan-Feng Xu 1 1 Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, China 2 Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, China 3 Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, China * These authors have contributed equally to this work Correspondence to: Xin-Gang Cui, email: xingangcui@126.com Dan-Feng Xu, email: nycnjc@126.com Keywords: GRO-α, CXCR2, bladder cancer, epithelial-mesenchymal transition, recurrence Received: March 24, 2016 Accepted: March 17, 2017 Published: April 03, 2017 ABSTRACT Non-muscle invasive bladder cancers (NMIBC) are typically treated by transurethral resection with intravesical chemotherapy. However, the post-therapeutic incidence of tumor recurrence and progression to muscle invasive disease is high, and the underlying mechanism(s) remains unknown. In this study, we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype, which is initiated by the autocrine GRO-α signaling. Mechanically, the chemotherapeutic drug epidoxorubicin induces GRO-α expression in primary bladder cancer cells at G1/S phase via p38-dependent activation of NF-κB. GRO-α phosphorylation of Snail on Ser246 supports Snail’s accumulation in the nucleus, and thereby promotes transcription repression activity of Snail from E-cadherin promoters. In accordance, disrupting the GRO-α-Snail axis in NMIBC represents a promising alternative to prevent post-therapeutic tumor progression and recurrence.

Purpose: We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort.Materials and Methods: This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard.Results: The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to h...

BACKGROUND Family history (FH) of prostate cancer (PCa) in Chinese population is poorly understood. The objective of this study is to evaluate the association between FH and PCa in a Chinese biopsy cohort. METHODS Consecutive patients who received 10 to 12 core systematic prostate biopsies from April 2013 to October 2018 in three medical centers were enrolled in this study. Demographic information and clinical information were obtained through prebiopsy questionnaire, including cancer FH, age, and total prostate-specific antigen (tPSA). RESULTS Of 2321 patients, 83 (3.6%) were reported a FH of PCa. The positive biopsy rate in these patients was 54.2%, significantly higher than the patients without the family history of PCa (42.6%; relative risk [RR] = 1.27; P = .024). In patients with positive FH of breast cancer gene (BRCA)-related cancers (breast, ovarian, and prostate cancer, n = 154), 74 (48.1%) were diagnosed as PCa, higher than those without FH (42.7%; RR = 1.13; P = .112). Multivariate logistic regression analysis (after adjusting for age and tPSA values) showed that there was 2.1-fold increased risk of PCa in patients with positive FH of PCa (P = .005), and 1.6-fold increased risk in patients with positive FH of BRCA-related cancers (P = .019). However, there was no significant association between FH of PCa or BRCA-related cancer and high-grade PCa after adjusting age and tPSA level (P = .404 for PCa, P = 0.991 for BRCA-related cancers). CONCLUSIONS Patients with positive FH of PCa had 2.1-fold higher risk of PCa, and patients with positive FH of BRCA-related cancers had 1.6-fold higher risk in this biopsy cohort of Chinese population. Patients with positive FH of PCa or BRCA-related cancers would have earlier age at onset of PCa.

Background Delayed gastric emptying and the resultant “full stomach” is the most important risk factor for perioperative pulmonary aspiration. Using point-of-care gastric sonography, we aimed to investigate the prevalence of full stomach and its risk factors in elective surgical patients with type 2 diabetes. Methods Type 2 diabetic and non-diabetic elective surgical patients were included from July 2017 to April 2018 in a 1:1 ratio. The study was retrospectively registered at July 2017, after enrollment of the first participant. Gastric ultrasound was performed 2 h after ingesting clear fluid or 6 h after a light meal. Full stomach was defined by the presence of gastric content in both semi-recumbent and right lateral decubitus positions. For patients with full or intermediate stomach, consecutive ultrasound scan was performed until empty stomach was detected. Logistic regression analyses were used to identify risk factors associated with full stomach. Results Fifty-two type 2 diabetic and fifty non-diabetic patients were analyzed. The prevalence of full stomach was 48.1% (25/52) in diabetic patients, with 44.0% for 2-h fast after clear fluid and 51.9% for 6-h fast after a light meal, significantly higher than 8% (4/50) in non-diabetic patients (P = 0.000). The average time to empty stomach in diabetic patients was 146.50 ± 40.91 mins for clear liquid and 426.50 ± 45.25 mins for light meal, respectively. Further analysis indicated that presence of diabetes-related eye disease was an independent risk factor of full stomach in diabetic patients (OR = 4.83, P = 0.010). Conclusions Almost half of type 2 diabetic patients have a full stomach following the current preoperative fasting guideline. Preoperative ultrasound assessment of gastric content in type 2 diabetic patients is suggested, especially for those with diabetes -related eye disease. Trial registration The trial was registered at www.clinicaltrials.gov with registration number NCT03217630. Retrospectively registered on 14th July 2017.