CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer.

Background: This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa. Method: A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8. Result: Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002). Conclusion: A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.

MEG3 interacted with miR-494 to repress bladder cancer progression through targeting PTEN.

The long noncoding RNA MEG3 is a significant tumor-suppressive gene in various tumors. But its biological role in bladder cancer remains uninvestigated. Herein, the biological mechanism of MEG3 in bladder cancer pathogenesis was explored. First, the expression of MEG3 in bladder cancer cells was examined, and we found that it was significantly reduced. In addition, in bladder cancer cells, we observed htat miR-494 was increased. Then, MEG3 was overexpressed in UMUC3 and SW780 cells and it could negatively modulate miR-494 expression. Bladder cancer cell proliferation was repressed, cell apoptosis was triggered and meanwhile, the cell cycle was remarkably arrested by the overexpression of MEG3. Moreover, the increase of MEG3 suppressed bladder cancer cell migration and invasion capacity. MEG3 can sponge miR-494 and the binding sites between them were confirmed by carrying out a series of functional assays. Furthermore, PTEN was speculated as a putative target of miR-494. Meanwhile, we found that miR-494 inhibitors induced PTEN. Finally, in vivo assays were conducted to prove that MEG3 can restrain bladder tumor growth by modulating miR-494 and PTEN. In conclusion, it was suggested MEG3 can interact with miR-494 to regulate PTEN in bladder cancer development.

Long non-coding RNA NEAT1 promotes bladder progression through regulating miR-410 mediated HMGB1.

LncRNA NEAT1 is reported as a crucial oncogene in multiple cancers. But, its biological role in bladder cancer is barely understood. Therefore, we concentrated on the function and role of NEAT1 in bladder cancer. Firstly, NEAT1 expression in bladder cancer cells was determined and it was displayed NEAT1 was significant elevated. NEAT1 was knockdown and overexpressed in T24 and J82 cells. Then it was indicated that NEAT1 silence greatly inhibited bladder cancer cell proliferation with an increased ratio of apoptotic cells and severe cell cycle arrest. Overexpression of NEAT1 exhibited a reversed process in bladder cancer cells. Additionally, in vivo experiments were employed using establishment of nude mice models. NEAT1 knockdown inhibited bladder cancer growth while increase of NEAT1 promoted bladder cancer development in vivo. By employing the bioinformatics analysis, we speculated that miR-410 was as a downstream target of NEAT1. Then, the targeting association between them was proved in our research and we implicated miR-410 was dramatically restrained in bladder cancer cells. Meanwhile, it was exhibited that miR-410 was negatively regulated by NEAT1. Apart from these, HMGB1 was speculated as a downstream target of miR-410. Dual-luciferase reporter assay was used to prove the correlation between miR-410 and HMGB1. Up-regulation of miR-410 restrained HMGB1 levels and NEAT1 can regulate HMGB1 level via sponging miR-410. To sum up, we implied NEAT1/miR-410/HMGB1 axis participated in bladder cancer.

Analysis of the reproductive outcomes and the size of the unicornuate uterus measured by magnetic resonance imaging and their relationship.

PURPOSE: To evaluate the relationship between the uterine size measured by pelvic magnetic resonance and reproductive outcome in women with a unicornuate uterus. METHODS: This was a retrospective study including 140 patients affiliated with unicornuate uterus diagnosed by the pelvic MR prior to their first pregnancy in the Obstetrics and Gynecology Hospital of Fudan University from April 2010 to December 2017. All the length of the unicornuate uterus were re-measured and recorded by skilled radiologists during the study period. We divided all the 140 participants with complete pelvic MR imaging into four groups by the best reproductive outcomes, which refers to Group 1 (primary infertility, n = 21), Group 2 ( < 24 weeks' gestation, n = 34), Group 3 (preterm delivery, 24-35 weeks' gestation, n = 13), Group 4 ( ≥ 35 weeks' gestation, n = 72), followed them up and then analyzed the data. RESULTS: Measurements of 140 patients with hemi-uteri were retrieved for analysis. The mean length of the uterine was 4.90  ± 0.56 cm. There were no significant differences in the uterine cavity length, cervical length, endometrial thickness and uterine wall thickness between the four groups while the uterine length (P = 0.001) was statistically significant. Women with uterine lengths ≥  4.5 cm were more likely to experience full-term delivery compared with the other group (P = 0.001). Ordinal multiple logistic regression analysis showed that the uterine length [OR = 9.03 (95% CI: 2.90-28.13)] and uterine cavity length [OR = 0.32 (95% CI: 0.06-2.04)] were independent protective factors for better obstetric outcomes CONCLUSION: The uterine length is a reliable prognostic factor for the gestational week of delivery and an appropriate antenatal surveillance factor of women with unicornuate uterus.

Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases.

Background: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. Methods: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing. The predictive cutoff value was independently validated using cohort I of 339 PCa patients (Southern China) and cohort II of 328 case patients (Germany, across China). Mann-Whitney U test, the receiver operating characteristic curve, McNemar's test, and logistic regression were used to assess data. All statistical tests were two-sided. Results: In the training set, CRMP4 promoter methylation (≥15.0% methylated) was statistically significantly associated with LNM (P < 001). Successful validations were achieved in both cohorts I and II (sensitivity = 92.3%, 95% confidence interval [CI] = 79.3 to 97.9, and sensitivity = 92.2%, 95% CI = 81.1 to 97.8, respectively; specificity = 92.7%, 95% CI = 80.2 to 99.1, and specificity = 91.3%, 95% CI = 87.4 to 94.4, respectively). The sensitivity of CRMP4 promoter methylation is superior to conventional MRI (cohort I: 92.3% vs 26.2%, P < 001; cohort II: 92.2% vs 33.3%, P < 001). CRMP4 promoter methylation is an independent predictor of LNM (cohort I: hazard ratio [HR] = 8.35, 95% CI = 5.64 to 12.35, P < 001; cohort II: HR = 12.46, 95% CI = 5.82 to 26.70, P < 001) in a multivariable analysis model. Conclusion: CRMP4 promoter methylation in diagnostic biopsies could be a robust biomarker for LNM in PCa.

Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting tubular epithelial-mesenchymal transition in vivo and in vitro.

Epithelial-mesenchymal transition (EMT) induces the progression of renal tubulointerstitial fibrosis. Astragalus membranaceus (AM) is a traditional Chinese herbal medicine that has been demonstrated to exert anti-inflammatory and anti-cancer effects, in addition to protecting and supporting the immune system. The present study investigated the effects of AM on renal fibrosis. A mouse model of unilateral ureteral obstruction (UUO) was established and treated with various concentrations of AM (100, 200 or 400 mg/kg/day). Interstitial fibrosis markedly increased in the UUO mice. AM significantly reduced the obstruction-induced upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin in the kidneys of the UUO mice (P<0.05). Furthermore, AM treatment significantly inhibited the induction of EMT and the deposition of extracellular matrix. In addition, a transforming growth factor (TGF)-ß1-stimulated murine renal proximal tubule cell line (NRK-52E) was treated with various concentrations of AM (10, 20, and 40 µg/ml). E-cadherin expression levels significantly decreased and those of α-SMA significantly increased in NRK-52E cells stimulated with TGF-ß1 in vitro (P<0.05). Co-treatment with AM reversed these effects (P<0.05), and AM treatment reduced TGF-ß1-induced expression and Smad2/3 phosphorylation (P<0.05). These results suggested that AM antagonizes tubular EMT by inhibiting the Smad signaling pathway.

[Partial pressure and diffusion flux of dissolved carbon dioxide in the mainstream and tributary of the central Three Gorges Reservoir in summer].

This study investigated the partial pressure of CO2 (pCO2) in the mainstream of the Three Gorges Reservoir and its tributary (Meixi River) in May 2013. Results showed that pCO2 in the surface water of the Meixi River and mainstream of the Three Gorges Reservoir was 6.8-7.5 Pa and 201.4-210.2 Pa, respectively. At the mixing area between the Meixi River and the mainstream of Changjiang, the lowest value of pCO2 in surface water was 53.5 Pa, and pCO2 gradually increased downwardly. Below 3 m in depth, pCO2 kept the stable value of around 210 Pa. Based on the calculation results, the emission flux of CO2 in the Meixi River and the mainstream of the central Three Gorges Reservoir was about -7.48 mmol x (m2 x d)(-1) and 39.58 mmol x (m2 x d)(-1), respectively. These results showed that the Meixi River is a sink for atmospheric CO2, and the mainstream of the Three Gorges Reservoir is a source for atmospheric CO2.

Characteristics of patients with fluid extravasation during retrograde ureteroscopic holmium laser lithotripsy for renal calculi.

OBJECTIVE: To explore the risk factors of fluid extravasation during retrograde ureteroscopic holmium laser lithotripsy for renal calculi. METHODS: Three hundred and twenty-seven patients with renal calculi ranging 10 to 20 mm received retrograde ureteroscopic holmium laser lithotripsy at Renmin Hospital of Wuhan University, Wuhan, China from January 2004 to December 2010. The clinical records were reviewed, and the correlation was studied between various clinical factors and fluid extravasation complications during operation. The clinical factors to be tested included patients' gender and age (<30, 30-50, and >50 years), hydronephrosis degree, previous intervention for renal calculi (none, shock-wave lithotripsy, and open surgery), upper urinary tract infection, ureteral access sheath placement, and procedure duration (<60, 60-120, and >120 mins). The data were processed by SPSS Version 16.0 statistical software, x2 test, and binary logistic regression were used for analysis. RESULTS: Fluid extravasation complications appeared in 35 patients. Patients` gender, age, and hydronephrosis degree were irrelevant to the occurrence of fluid extravasation, while having previous open surgery for renal calculi, without ureteral access sheath placement, upper urinary tract infection, and long procedure duration were all responsible for higher incidence of the complications. CONCLUSION: Reasonable selection of patients, effective control of upper urinary tract infection, routine ureteral access sheath placement, and controlling procedure duration help to decrease the incidence of fluid extravasation complications in retrograde ureteroscopic holmium laser lithotripsy for renal calculi.

[Treatment of buried penis in children with fixation at the dartos coat of penis through prepubic route].

OBJECTIVE: To observe the long-time results of the treatment of buried penis with fixation at the base of penis through pre-pubic route. METHODS: From Aug 2002 to Dec 2003, the procedure was performed in 34 children without penile skin insufficiency. The major technique involved the release of hided penis shaft by partly shearing suspensory ligament, fixating the bucks fascia and tunica albuginea at 3 and 9 o'clock positions with the subcutaneous penile skin at the base of penis just under the pubic symphysis. RESULTS: Twenty-one patients have been reviewed over one year with satisfactory appearance. Thirteen patients were lost to follow-up. No recurrence happened in our group. CONCLUSION: We compare this technique with major treatment methods for buried penis in children at present, and we conclude this technique is a reasonable, simplified and aesthetical method for the treatment of buried penis in children.