Publications by authors named "Shaogang Wang"

160 Publications

Intra-abdominal robot-assisted vasovasostomy of obstructive azoospermia in an Asian population following multiple bilateral inguinal herniorrhaphy in childhood: a case report and literature review.

Transl Androl Urol 2021 Jun;10(6):2521-2527

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Iatrogenic injury to the vas deferens is an indication for vasovasostomy (VV). Various surgical approaches, including pure microsurgical VV (MVV), pelviscrotal laparoscopic-assisted VV (LAVV), and intra-abdominal robot-assisted VV (RAVV), have been reported to restore vasal patency. MVV is often faced a formidable challenge to provide tension-free VV due to an inadequate vas deferens length. Alternatively, pelviscrotal LAVV is much more effective for the identification and retrieval of the pelvic vas deferens prior to performing MVV. However, vasal laparoscopic mobilization could still be limited by insufficient vasal length for extracorporeal transfer in some cases. The addition of robotic assistance, on the other hand, allows the performance of "in-situ" vasal anastomoses and offers unique features compared with pure MVV/LAVV. However, few such approaches have been described in the literature. This study presents the initial results and validation of robot-assisted VV in an Asian population who had undergone triple herniorrhaphy. Briefly, Intra-operative findings demonstrated a large defect of the vas deferens, and a two-layer bilateral tension-free RAVV was performed to pursue the possibility of naturally achieved pregnancy. With our promising results, intra-abdominal RAVV may be described as a practical approach for cases with iatrogenic large defects of the vas deferens within the inguinal canal.
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http://dx.doi.org/10.21037/tau-21-133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261426PMC
June 2021

Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer.

Front Genet 2021 22;12:574196. Epub 2021 Jun 22.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Post-transcriptional regulation plays a leading role in gene regulation and RNA binding proteins (RBPs) are the most important posttranscriptional regulatory protein. RBPs had been found to be abnormally expressed in a variety of tumors and is closely related to its occurrence and progression. However, the exact mechanism of RBPs in bladder cancer (BC) is unknown. We downloaded transcriptomic data of BC from the Cancer Genome Atlas (TCGA) database and used bioinformatics techniques for subsequent analysis. A total of 116 differentially expressed RBPs were selected, among which 61 were up-regulated and 55 were down-regulated. We then identified 12 prognostic RBPs including , and , and constructed a prognostic risk score model. Based on this model we found that patients in the high-risk group had poorer overall survival ( < 0.001), and the area under the receiver operator characteristic curve for this model was 0.677 for 1 year, 0.697 for 3 years, and 0.709 for 5 years. Next, we drew a nomogram based on the risk score and other clinical variables, which showed better predictive performance. Our findings contribute to a better understanding of the pathogenesis, progression and metastasis of BC. The model of these 12 genes has good predictive value and may have good prospects for improving clinical treatment regimens and patient prognosis.
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http://dx.doi.org/10.3389/fgene.2021.574196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258248PMC
June 2021

α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation.

Nat Commun 2021 07 5;12(1):4113. Epub 2021 Jul 5.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

Tri-methylation on lysine 40 of α-tubulin (α-TubK40me3) is a recently identified post-translational modification involved in mitosis and cytokinesis. However, knowledge about α-TubK40me3 in microtubule function and post-mitotic cells remains largely incomplete. Here, we report that α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. α-TubK40me3 is enriched in mouse cerebral cortex during embryonic day (E)14 to E16. Knockdown of α-tubulin methyltransferase SETD2 at E14 leads to the defects in neuronal migration, which could be restored by overexpressing either a cytoplasm-localized SETD2 truncation or α-TubK40me3-mimicking mutant. Furthermore, α-TubK40me3 is preferably distributed on polymerized microtubules and potently promotes tubulin nucleation. Downregulation of α-TubK40me3 results in reduced microtubule abundance in neurites and disrupts neuronal polarization, which could be rescued by Taxol. Additionally, α-TubK40me3 is increased after losing α-tubulin K40 acetylation (α-TubK40ac) and largely rescues α-TubK40ac function. This study reveals a critical role of α-TubK40me3 in microtubule formation and neuronal development.
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http://dx.doi.org/10.1038/s41467-021-24376-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257576PMC
July 2021

The Activation of ROS/NF-B/MMP-9 Pathway Promotes Calcium-Induced Kidney Crystal Deposition.

Oxid Med Cell Longev 2021 8;2021:8836355. Epub 2021 Jun 8.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague-Dawley rats with 1,25(OH)D-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial-osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-B/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.
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http://dx.doi.org/10.1155/2021/8836355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208877PMC
June 2021

Risk Assessment and Prevention of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission for Hospitalized Urological Patients After the COVID-19 Pandemic in Wuhan, China.

Eur Urol Open Sci 2020 Jul 30;20:20-27. Epub 2020 Jul 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Emerging asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected and multiple cases were found to be SARS-CoV-2 positive again, which raised an alarm for the patients hospitalized after the coronavirus disease 2019 (COVID-19) pandemic.

Objective: We investigated the risk and prevention of hospital transmission of SARS-CoV-2 to hospitalized urological patients.

Design Setting And Participants: This is a retrospective study of 319 hospitalized urological patients enrolled between April 20, 2020 and May 11, 2020 from two tertiary hospitals in Wuhan, China.

Intervention: Chest computed tomography (CT) images, nucleic acid tests (NATs), and serum antibody were examined at the outpatient department and 1 wk after admission for all patients.

Outcome Measurements And Statistical Analysis: The chest CT images, NATs, serum antibody results, and clinical data were collected and analyzed.

Results And Limitations: None of the 319 patients was found to be SARS-CoV-2 NAT positive. Ten and four patients were detected to be immunoglobulin (Ig)G and IgM positive, respectively. The chest CT features of 116 patients showed abnormal lung findings. During the 1-wk isolation, one patient initially being IgG positive only was found to be IgM positive, and another initially IgM-positive patient had a rising IgG level. Through risk assessment, we identified seven patients with very high and high risk for hospital transmission, and delayed the surgery while maintaining close follow-up. Five intermediate-risk patients were operated on successfully under paravertebral block or epidural anesthesia to avoid opening the airway with endotracheal intubation. The remaining 104 low-risk and 203 normal patients underwent normal surgery.

Conclusions: Of the 319 patients, seven were identified as very high and high risk, which reinforced the importance of epidemic surveillance of discharged COVID-19 patients and asymptomatic infections. Five intermediate-risk patients were operated on successfully under regional anesthesia.

Patient Summary: Our experience of risk assessment and management practice may provide a strategy to prevent severe acute respiratory syndrome coronavirus 2 transmission to hospitalized urological patients after the coronavirus disease 2019 (COVID-19) pandemic.
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http://dx.doi.org/10.1016/j.euros.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392039PMC
July 2020

Lower Urinary Tract Symptoms and Sexual Dysfunction in Male: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 28;8:653510. Epub 2021 May 28.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

An association between lower urinary tract symptoms (LUTS) and risk of sexual dysfunction in male remains controversial in recent decades. PubMed and Web of Science were searched up to October 28, 2020, for articles reporting the prevalence of sexual dysfunction in men with LUTS. The main outcomes were results from sexual dysfunction assessments. Pooled odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were calculated. The quality assessment of the included studies was performed by using The Newcastle-Ottawa Scale (NOS) or JBI Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). A total of 24 full-manuscript papers met the inclusion criteria. The pooled OR for 21 studies suggested that patients with severer LUTS had a higher risk of sexual dysfunction (OR = 3.31, 95% CI: 2.43 to 4.49, < 0.001, = 90%). A significant decrease in scores of assessment tools for sexual dysfunction was observed in the patients with higher severity of LUTS compared with those patients with lower severity (WMD = -5.49, 95%CI: -7.25 to -3.27, P < 0.001, = 96%). Similar outcomes were also found in subgroup analyses. In a detailed analysis of specific sexual function domains, the severity of LUTS was associated with erectile dysfunction, intercourse satisfaction, and overall satisfaction, except for sexual desire. The study demonstrates an association between exposure of lower urinary tract symptoms and risk of sexual dysfunction in male. Assessment of sexual function is necessary for patients with lower urinary tract symptoms. http://www.crd.york.ac.uk/prospero, identifier: CRD42020208747.
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http://dx.doi.org/10.3389/fmed.2021.653510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193225PMC
May 2021

JAK2 deficiency improves erectile function in diabetic mice through attenuation of oxidative stress, apoptosis, and fibrosis.

Andrology 2021 Jun 3. Epub 2021 Jun 3.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Janus kinase 2 (JAK2) is activated in diabetic mellitus (DM) conditions and may enhance oxidative stress, apoptosis and fibrosis in many tissues. Whether JAK2 activation is involved in the occurrence of diabetic erectile dysfunction (ED) is unknown.

Objectives: We performed this study to investigate the effect of JAK2 deficiency on diabetic ED.

Materials And Methods: Conditional JAK2 gene knockout mice (Cre -JAK2 ) were used, in which JAK2 gene knockout could be induced by tamoxifen. Mice fell into four groups: control, JAK2 knockout (JAK2 ), DM, and DM with JAK2 . DM was induced by intraperitoneal injection of streptozotocin. Two months later, JAK2 gene knockout was induced with tamoxifen in Cre -JAK2 mice. After another 2 months, erectile function was measured by electrical stimulation of the cavernous nerve, and penile tissues were harvested. Ratio of maximal intracavernosal pressure (MIP) to mean arterial blood pressure (MAP), expression and phosphorylation of JAK2, oxidative stress level, NO/Cyclic Guanosine Monophosphate (cGMP) pathway, apoptosis, fibrosis, and transforming growth factor beta 1 (TGF-β1)/Smad/Collagen IV pathway in corpus cavernosum, were measured.

Results: JAK2 expression was remarkably decreased after induction with tamoxifen. JAK2 was activated in penile tissues of diabetic mice, and JAK2 deficiency could improve the impaired erectile function caused by DM. However, in mice without DM, JAK2 deficiency had no apparent influence on erectile function. Levels of oxidative stress, apoptosis, fibrosis, and TGF-β1/Smad/Collagen IV pathway were all elevated by DM, whereas JAK2 deficiency lessened these alterations in diabetic mice. Moreover, JAK2 deficiency improved the expression of the down-regulated NO/cGMP pathway in diabetic mice. In non-diabetic mice, no apparent changes were found in aforementioned parameters after JAK2 gene knockout.

Discussion And Conclusion: Our study showed that JAK2 deficiency could improve erectile function in diabetic mice, which might be mediated by reduction in oxidative stress, apoptosis, and fibrosis in corpus cavernosum.
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http://dx.doi.org/10.1111/andr.13061DOI Listing
June 2021

Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy.

Front Cell Dev Biol 2021 13;9:659294. Epub 2021 May 13.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort ( = 530) and GEO cohort ( = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to "immune desert phenotype," "immune resistance phenotype," and "immune-inflammatory phenotype," respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients' ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.
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http://dx.doi.org/10.3389/fcell.2021.659294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158301PMC
May 2021

A partial loss-of-function variant in gene in a Chinese cohort with idiopathic hypogonadotropic hypogonadism.

Transl Androl Urol 2021 Apr;10(4):1676-1687

Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease attributed to the disorder of hypothalamic-pituitary-gonadal axis. Mutations in the gene are one of the most common genetic causes of IHH. Herein, we aimed to investigate variants in a Chinese cohort with IHH, and to characterize them at the molecular level.

Methods: A total of 153 IHH patients were recruited, and variants were detected using a tailored next-generation sequencing panel. rare sequencing variant (RSV) was verified using Sanger sequencing. Phenotypic features and therapeutic outcomes of patients were followed up. In order to examine the pathogenicity of the RSV, we performed conservative analysis, crystal structure prediction, expression analysis as well as the assessment of ERK1/2 activation and IP3/Ca response.

Results: The same heterozygous RSV (p.R240Q) in was identified in four sporadic IHH patients. These patients exhibited different severity of testicular development and hormone profile. hCG treatment was effective in improving gonadal development, serum testosterone, and semen quality. The RSV has no effect on the expression of mRNA and protein, whereas damaged ERK1/2 activation and inositol triphosphate/calcium signaling.

Conclusions: The study expands mutation spectrum in IHH patients, and reveals that the RSV is a partial loss-of-function mutation. Although this heterozygous RSV may not have a significant influence on the pathogenesis of IHH, but its homozygous/ compound status should be paid attention in this research field.
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http://dx.doi.org/10.21037/tau-20-1390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100836PMC
April 2021

Phosphorylation of the androgen receptor at Ser81 is co-sustained by CDK1 and CDK9 and leads to AR-mediated transactivation in prostate cancer.

Mol Oncol 2021 Jul 3;15(7):1901-1920. Epub 2021 May 3.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re-activation still remains a major challenge during treatment of castration-resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81-phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR-mediated transactivation with the chromatin locus openness. Moreover, pS81-specific ChIP-Seq showed a disproportional occupancy of pS81 on AR-activated promoters, while 3C-ChIP assays further indicated an enrichment of pS81 at the PSA enhancer-promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re-ChIP assays also confirmed that AR-dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin-bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.
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http://dx.doi.org/10.1002/1878-0261.12968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253089PMC
July 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

Urol Int 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety.

Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups.

Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315).

Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
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http://dx.doi.org/10.1159/000514042DOI Listing
March 2021

Ureteroscopic lithotripsy combined with paravertebral block anesthesia or general anesthesia: A propensity matched case-control study.

Asian J Surg 2021 Mar 26. Epub 2021 Mar 26.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: To evaluate the safety, efficacy and cost of paravertebral block anesthesia for ureteral stones patients undergoing ureteroscopic lithotripsy.

Methods: Four hundred and eighty-two patients who underwent ureteroscopy for unilateral ureteral stones were incorporated into our retrospective study. A propensity-matched comparison in patients with paravertebral nerve block anesthesia (PVB) group and general anesthesia (GA) group was performed. Intraoperative hemodynamic parameters, operative time, visual analog scale for pain, stone-free rate, anesthetic cost and postoperative hospital stay were compared between the two groups.

Results: Sixty-one GA cases were propensity matched to 61 PVB cases. In the PVB group, all the procedures were completed successfully without anesthesia conversion. Significantly less intraoperative severe hypotensive (P = 0.002) and arrhythmia (P < 0.001) episodes in PVB group. There were no significant differences in operative time (p = 0.702), initial stone-free rate (p = 0.686), and total stone-free rate (p = 0.794) between the two groups. The PVB group had lower postoperative pain and prolonged analgesia (p = 0.007). The postoperative hospital stay in the PVB group was significantly shorter (3.20 ± 0.73 vs 3.84 ± 1.32 d, p = 0.001). And the cost of anesthesia was lower in the PVB group (195.47 ± 13.01 vs 396.31 ± 36.45 US dollars, p < 0.001).

Conclusion: Under PVB anesthesia, URS can be successfully completed without anesthetic transformation, and its efficacy and safety have been demonstrated. When economic aspects are taken into consideration, PVB seems to be a more economical and effective anesthetic method of URS.
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http://dx.doi.org/10.1016/j.asjsur.2021.03.001DOI Listing
March 2021

Resveratrol Attenuates Oxalate-Induced Renal Oxidative Injury and Calcium Oxalate Crystal Deposition by Regulating TFEB-Induced Autophagy Pathway.

Front Cell Dev Biol 2021 25;9:638759. Epub 2021 Feb 25.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The oxidative injury of renal tubular epithelial cells caused by inflammation and oxidative stress induced by hyperoxaluria is an important factor in the kidney calcium oxalate (CaOx) stone formation. Resveratrol (RSV) has been reported to reduce oxidative injury to renal tubular epithelial cells, and autophagy is critical for the protective effect of resveratrol. However, the protective mechanism of RSV in oxalate-induced oxidative injury of renal tubular cells and the role of autophagy in this process are still unclear. In our study, glyoxylic acid monohydrate-induced rats were treated with or without resveratrol, and it was detected that the overexpression of oxidant species, CaOx crystal deposition, apoptosis level, inflammatory cytokines and osteoblastic-associated protein expression were reversed by resveratrol. Additionally, Resveratrol pretreatment significantly reversed oxalate -induced decline in cell viability, cell damage, oxidant species overexpression, and osteogenic transformation in normal rat kidney epithelial-like (NRK-52E) cells. Furthermore, we found that RSV pretreatment promoted intracellular LC3II upregulation, p62 downregulation, and autophagosome formation, whereas 3-methyladenine treatment reduced this effect. Moreover, RSV induced the expression of transcription factor EB (TFEB) in the nucleus of NRK-52E cells in a concentration-dependent manner. After transfection of NRK-52E cells with TFEB siRNA, we showed that the RSV-induced increase in TFEB expression and autophagosome formation were inhibited. Simultaneously, RSV-induced NRK-52E cells protection was partially reversed. These results suggested that RSV regulates oxalate-induced renal inflammation, oxidative injury, and CaOx crystal deposition and through the activation of a TFEB-induced autophagy.
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http://dx.doi.org/10.3389/fcell.2021.638759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947311PMC
February 2021

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic.

Transl Androl Urol 2021 Jan;10(1):466-474

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: To introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19).

Methods: All emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study's COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods.

Results: The total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% 15%, P=0.027) and single-J stent-related problems (19% 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period.

Conclusions: Urological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.
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http://dx.doi.org/10.21037/tau-20-1194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844486PMC
January 2021

Transcriptome Analyses Identify an RNA Binding Protein Related Prognostic Model for Clear Cell Renal Cell Carcinoma.

Front Genet 2020 7;11:617872. Epub 2021 Jan 7.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

RNA binding proteins (RBPs) play a key role in post-transcriptional gene regulation. They have been shown to be dysfunctional in a variety of cancers and are closely related to the occurrence and progression of cancers. However, the biological function and clinical significance of RBPs in clear cell renal carcinoma (ccRCC) are unclear. In our current study, we downloaded the transcriptome data of ccRCC patients from The Cancer Genome Atlas (TCGA) database and identified differential expression of RBPs between tumor tissue and normal kidney tissue. Then the biological function and clinical value of these RBPs were explored by using a variety of bioinformatics techniques. We identified a total of 40 differentially expressed RBPs, including 10 down-regulated RBPs and 30 up-regulated RBPs. Eight RBPs (, and ) and nine RBPs (, and ) were identified as prognostic related to overall survival (OS) and disease-free survival (DFS), respectively, and prognostic models for OS and DFS were constructed based on these RBPs. Further analysis showed that OS and DFS were worse in high-risk group than in the low-risk group. The area under the receiver operator characteristic curve of the model for OS was 0.702 at 3 years and 0.726 at 5 years in TCGA cohort and 0.783 at 3 years and 0.795 at 5 years in E-MTAB-1980 cohort, showing good predictive performance. Both models have been shown to independently predict the prognosis of ccRCC patients. We also established a nomogram based on these prognostic RBPs for OS and performed internal validation in the TCGA cohort, showing an accurate prediction of ccRCC prognosis. Stratified analysis showed a significant correlation between the prognostic model for OS and ccRCC progression.
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http://dx.doi.org/10.3389/fgene.2020.617872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817999PMC
January 2021

Analysis of cardiovascular risks for erectile dysfunction in Chinese patients with type 2 diabetes mellitus lacking clinical symptoms of cardiovascular diseases.

Transl Androl Urol 2020 Dec;9(6):2500-2509

Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Erectile dysfunction (ED) is common but usually underdiagnosed in diabetics. The correlation between different vascular lesions and ED in diabetics without clinical cardiovascular symptoms is unknown. The aim was to explore the association between cardiovascular risks and ED in Chinese type 2 diabetic men lacking clinical performance.

Methods: Erectile function of patients with type 2 diabetes was assessed by the 5-item International Index of Erectile Function (IIEF-5) questionnaire. The data of clinical characteristics and vascular lesions at carotid and lower limb sites assessed by the Doppler ultrasound were collected to evaluate diabetes- metabolic indices. Univariate and multivariate analyses were conducted to find statistical correlation between cardiovascular risks and diabetic ED.

Results: A total of 71.21% reported suffering from ED. Lower limb plaques were more common (45.38%) than carotid district (35.62%) in diabetes. Men with ED had higher carotid intima-media thickness (IMT) (P<0.001) and the presence of lower limb plaques (P<0.001) compared with men without ED. After adjusting for age, diabetic duration, blood pressure (BP) and antidiabetic medication, carotid IMT greater than 0.75 mm (P<0.001) and the presence of lower limb plaques (P=0.051) remained associated with the presence of ED and its severity. Compared with isolated atherosclerosis at carotid or lower limb district, vascular lesions at any site and both sites were more correlative with ED presence (all P<0.001).

Conclusions: The prevalence of ED is high among Chinese diabetic men. A higher carotid IMT and the presence of lower limb plaques indicate a tight correlation between peripheral atherosclerosis and diabetic ED. ED may be the only clinical association of symptomatic cardiovascular diseases (CVDs) in diabetes. It is significant to screen ED to prevent the further development of severe symptomatic CVDs.
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http://dx.doi.org/10.21037/tau-20-999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807359PMC
December 2020

Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

Front Oncol 2020 30;10:562504. Epub 2020 Nov 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The prognostic value of androgen receptor splice variant 7 (AR-V7) for the treatment response of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we aimed to synthesize relevant studies that assessed the prognostic value of AR-V7 status for the treatment response of mCRPC patients treated with androgen receptor signalling inhibitors (ARSis) and chemotherapy.

Methods: We searched the PubMed, Embase, and MEDLINE databases by using the keywords and to identify relevant studies published before 25 September 2019. The main outcomes were prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS). Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale.

Results: A total of 1,545 patients from 21 studies were included. For the mCRPC patients treated with ARSis, AR-V7-positive patients had a lower PSA response rate (OR 6.01, 95% CI 2.88-12.51; < 0.001), shorter PFS (HR 2.56, 95% CI 1.80-3.64;  < 0.001) and shorter OS (HR 4.28, 95% CI 2.92-6.27; < 0.001) than AR-V7-negative patients. Although AR-V7-positive patients treated with chemotherapy also had a lower PSA response rate (OR 2.23, 95% CI 1.38-3.62; = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02-2.53; = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74-1.49; = 0.796) between these groups. Furthermore, AR-V7-positive patients receiving ARSis had a shorter median OS than those receiving chemotherapy (HR 3.50, 95% CI 1.98-6.20; < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64-2.62;  = 0.47).

Conclusions: AR-V7 is a potential biomarker of treatment resistance in mCRPC patients. AR-V7-positive mCRPC patients had poorer treatment outcomes than AR-V7-nagetive patients when treated with ARSis. AR-V7-positive patients have better outcomes when treated with taxane than ARSis. Furthermore, the ability of AR-V7 status to predict treatment outcomes varies from different detection methods. The detection of AR-V7 before treatment is important for the selection of treatment modalities for mCRPC patients.
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http://dx.doi.org/10.3389/fonc.2020.562504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735106PMC
November 2020

An eleven metabolic gene signature-based prognostic model for clear cell renal cell carcinoma.

Aging (Albany NY) 2020 11 18;12(22):23165-23186. Epub 2020 Nov 18.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.

In this study, we performed bioinformatics and statistical analyses to investigate the prognostic significance of metabolic genes in clear cell renal cell carcinoma (ccRCC) using the transcriptome data of 539 ccRCC and 72 normal renal tissues from TCGA database. We identified 79 upregulated and 45 downregulated (n=124) metabolic genes in ccRCC tissues. Eleven prognostic metabolic genes () were identified by further analysis. We then constructed an 11-metabolic gene signature-based prognostic risk score model and classified ccRCC patients into high- and low-risk groups. Overall survival (OS) among the high-risk ccRCC patients was significantly shorter than among the low-risk ccRCC patients. Receiver operating characteristic (ROC) curve analysis of the prognostic risk score model showed that the areas under the ROC curve for the 1-, 3-, and 5-year OS were 0.810, 0.738, and 0.771, respectively. Thus, our prognostic model showed favorable predictive power in the TCGA and E-MTAB-1980 ccRCC patient cohorts. We also established a nomogram based on these eleven metabolic genes and validated internally in the TCGA cohort, showing an accurate prediction for prognosis in ccRCC.
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http://dx.doi.org/10.18632/aging.104088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746370PMC
November 2020

Albumin-globulin ratio: a novel predictor of sepsis after flexible ureteroscopy in patients with solitary proximal ureteral stones.

Transl Androl Urol 2020 Oct;9(5):1980-1989

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: To identify predictors of sepsis after flexible ureteroscopy (fURS) in patients with unilateral, solitary, proximal ureteral stones and evaluate the association between albumin-globulin ratio (AGR) and sepsis.

Methods: Overall, 759 patients who underwent fURS were retrospectively enrolled. Univariate and multivariate logistic regression analyses were performed to identify predictors of sepsis after fURS in patients with solitary proximal ureteral stones. Then A nomogram was generated using the predictors.

Results: Sepsis occurred in 43 patients (5.7%), and 6 (0.8%) of them developed septic shock. Univariate analysis showed that age, female sex, albumin concentration, globulin concentration, AGR, pre-operative fever, white blood cell (WBC) count, urine culture (UC) result, urine WBC count, and urine nitrite result were predictors of sepsis. Multivariate analysis identified AGR <1.2 [odds ratio (OR) =2.810, 95% confidence interval (CI): 1.245-6.342, P=0.013] and positive UC (OR =10.520, 95% CI: 4.489-24.653, P<0.001) as independent predictors. When AGR <1.2 and positive UC were combined, area under the receiver operator characteristic curve was 0.825. Then patients were categorized by different AGR level ("≥1.4", "1.2-1.4", "1.0-1.2", "<1.0"), and corresponding sepsis rates were 27.7%, 9.8%, 4.5% and 2.5%.

Conclusions: Positive UC and low AGR were independent predictors of post-fURS sepsis. Cautious pre-operative evaluation and optimized treatment strategy should be considered to minimize infectious complications.
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http://dx.doi.org/10.21037/tau-20-823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658149PMC
October 2020

A Novel Clinical-Radiomics Model Pre-operatively Predicted the Stone-Free Rate of Flexible Ureteroscopy Strategy in Kidney Stone Patients.

Front Med (Lausanne) 2020 15;7:576925. Epub 2020 Oct 15.

Russell H. Morgan Department of Radiology and Radiological Science, the Johns Hopkins Medical Institutions, Baltimore, MD, United States.

The purpose of the study is to develop and validate a novel clinical-radiomics nomogram model for pre-operatively predicting the stone-free rate of flexible ureteroscopy (fURS) in kidney stone patients. Altogether, 2,129 fURS cases with kidney stones were retrospectively analyzed, and 264 patients with a solitary kidney stone were included in a further study. For lower calyx calculi, a radiomics model was generated in a primary cohort of 99 patients who underwent non-contrast-enhanced computed tomography (NCCT). Radiomics feature selection and signature building were conducted by using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was employed to build a model incorporating radiomics and potential clinical factors. Model performance was evaluated by its discrimination, calibration, and clinical utility. The model was internally validated in 43 patients. The overall success rate of fURS was 72%, while the stone-free rate (SFR) for lower calyx calculi and non-lower calyx calculi was 56.3 and 90.16%, respectively. On multivariate logistic regression analysis of the primary cohort, independent predictors for SFR were radiomics signature, stone volume, operator experience, and hydronephrosis level, which were all selected into the nomogram. The area under the curve (AUC) of clinical-radiomics model was 0.949 and 0.947 in the primary and validation cohorts, respectively. Moreover, the calibration curve showed a satisfactory predictive accuracy, and the decision curve analysis indicated that the nomogram has superior clinical application value. In this novel clinical-radiomics model, the radiomics scores, stone volume, hydronephrosis level, and operator experience were crucial for the flexible ureteroscopy strategy.
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http://dx.doi.org/10.3389/fmed.2020.576925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593485PMC
October 2020

No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation.

Andrology 2021 01 23;9(1):99-106. Epub 2020 Nov 23.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The coronavirus disease 2019 (COVID-19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID-19 patients is limited or unknown.

Objectives: To comprehensively evaluate urogenital involvement in recovered COVID-19 patients.

Materials And Methods: Men aged between 20 years and 50 years who were diagnosed with SARS-CoV-2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS-CoV-2 RNA detection. Semen quality and hormonal profiles were analyzed.

Results: Among 74 male recovered COVID-19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID-19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT-PCR test and semen samples collection was 80 days (IQR, 64-93). The median age was 31 years (IQR, 27-36; range, 21-49), and the median body mass index (BMI) was 24.40 (IQR, 22.55-27.30). Forty-five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty-three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID-19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS-CoV-2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID-19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID-19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study.

Discussion And Conclusions: To the best of our knowledge, it is the largest cohort study with longest follow-up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow-up on the reproductive function in the following months.
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http://dx.doi.org/10.1111/andr.12939DOI Listing
January 2021

Exosomes derived from smooth muscle cells ameliorate diabetes-induced erectile dysfunction by inhibiting fibrosis and modulating the NO/cGMP pathway.

J Cell Mol Med 2020 11 3;24(22):13289-13302. Epub 2020 Oct 3.

Department of Urology and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.

Erectile dysfunction (ED) is a major health issue among men with diabetes, and ED induced by diabetes mellitus (DMED) is particularly difficult to treat. Therefore, novel therapeutic approaches for the treatment of DMED are urgently needed. Exosomes, nanosized particles involved in many physiological and pathological processes, may become a promising tool for DMED treatment. In this study, we investigated the therapeutic effect of exosomes derived from corpus cavernosum smooth muscle cells (CCSMC-EXOs) on erectile function in a rat model of diabetes and compared their effect with that of exosomes derived from mesenchymal stem cells (MSC-EXOs). We incubated labelled CCSMC-EXOs and MSC-EXOs with CCSMCs and then observed uptake of the exosomes at different time points using laser confocal microscopy. CCSMC-EXOs were more easily taken up by CCSMCs. The peak concentration and retention time of labelled CCSMC-EXOs and MSC-EXOs in the corpus cavernosum of DMED rats after intracavernous injection were compared by in vivo imaging techniques. Intracavernous injection of CCSMC-EXOs was associated with a relatively high peak concentration and long retention time. Our data showed that CCSMC-EXOs could improve erectile function in DMED rats. Meanwhile, CCSMC-EXOs could exert antifibrotic effects by increasing the smooth muscle content and reducing collagen deposition. CCSMC-EXOs also increased the expression of eNOS and nNOS, followed by increased levels of NO and cGMP. These findings initially identify the possible role of CCSMC-EXOs in ameliorating DMED through inhibiting corporal fibrosis and modulating the NO/cGMP signalling pathway, providing a theoretical basis for a breakthrough in the treatment of DMED.
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http://dx.doi.org/10.1111/jcmm.15946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701535PMC
November 2020

An isolated hypogonadotropic hypogonadism male with a novel de novoFGFR1 mutation fathered a normal son evidenced by prenatal genetic diagnosis.

Andrologia 2020 Dec 29;52(11):e13821. Epub 2020 Sep 29.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.

Isolated hypogonadotropic hypogonadism (IHH) is a rare but treatable form of male infertility caused by congenital defect in gonadotropin-releasing hormone (GnRH) secretion or action. We report a Chinese IHH male with a novel FGFR1 mutation who successfully fathered a normal son. Targeted next-generation sequencing, bioinformatics analysis and Sanger sequencing were performed by using the DNA extracted from the pedigree. The patient was treated with gonadotropin and was able to impregnant his wife during the treatment. Amniocentesis was performed at the 18 weeks of gestation. A novel de novo pathogenic missense variant (c.980A>G, p.Asn327Ser) in exon 8 in FGFR1 gene (NM_001174067.1) was identified in the patient but not in his normal parents. This variant was also absent in the DNA obtained from the amniocentesis sample. His son has normal growth and development at the age of 2 years. This is the first case of prenatal genetic diagnosis based on the genetic testing of the IHH father by combining targeted next-generation and Sanger sequencing in IHH family. We extended the mutation spectrum of FGFR1 in IHH patients. Prenatal genetic diagnosis based on the results of genetic testing of the IHH patients may be helpful in the genetic counselling for the IHH families.
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http://dx.doi.org/10.1111/and.13821DOI Listing
December 2020

Quantitative proteomic analysis of urinary exosomes in kidney stone patients.

Transl Androl Urol 2020 Aug;9(4):1572-1584

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Increased urinary exosomes are associated with kidney stones but how they work is unknown. In this study, we aim to identify dysregulated proteins in urinary exosomes from kidney stone patients and to explore the potential role of exosomal proteins in nephrolithiasis.

Methods: First morning voids were collected from participants. Urinary exosomes were isolated via ultracentrifugation. Label free liquid chromatography-tandem mass spectrometry was performed to analyze the proteome of urine exosomes from three kidney stone patients and three age-/sex-matched healthy controls. Bioinformatics analysis was conducted to identify dysregulated proteins associated with stone formation. Results of proteomic analysis were verified by Western blotting in other three kidney stone patients and three healthy controls.

Results: Nine hundred and sixty proteins were identified with proteomic analysis, of which 831 were identified in the control group and 879 in the stone group. Sixteen proteins in urinary exosomes were found most significantly different between kidney stone patients and healthy controls. Gene ontology (GO) analysis showed that dysregulated proteins were enriched in innate immune response, defense response to bacterium and calcium-binding. S100A8, S100A9 and S100A12 were common in above three GO terms and were chosen for further study. Western blotting confirmed that the expression of these three S100 proteins was higher in urinary exosomes from kidney stone patients. In addition, S100 proteins were aggregated in urinary exosomes and it was difficult to detect them in urine.

Conclusions: Urinary exosomes from kidney stone patients are rich in S100 proteins and play a role in innate immune response, defense response to bacterium and calcium-binding.
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http://dx.doi.org/10.21037/tau-20-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475656PMC
August 2020

Liraglutide Ameliorates Erectile Dysfunction Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus.

Front Pharmacol 2020 12;11:1257. Epub 2020 Aug 12.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms and .

Methods: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. , effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins.

Results: Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor.

Conclusion: Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.
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http://dx.doi.org/10.3389/fphar.2020.01257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435068PMC
August 2020

The role of adrenal venous sampling and computed tomography in the management of primary aldosteronism.

J Hypertens 2021 Feb;39(2):310-317

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, PR China.

Background: The role of adrenal venous sampling (AVS) has been challenged by some recent evidence. This study aimed to compare the role of AVS and computed tomography (CT) in the management of primary aldosteronism.

Methods: Patients who underwent unilateral adrenalectomy for primary aldosteronism at a single center between January 2015 and December 2018 were included, and postoperative outcomes of the patients who underwent surgery based on CT (n = 195) or AVS (n = 40) were compared. The data of all the patients who underwent AVS successfully (n = 75) during this period were also collected and analyzed.

Results: There were no significant differences between the CT-guided and AVS-guided adrenalectomies in most of the postoperative outcomes, and the proportion of patients achieving cure of hypokalemia (CT vs. AVS, 98.3 vs. 96.4%) and alleviation of hypertension (89.2 vs. 92.9%) were similar between the two groups. However, since the baseline characteristics of the two groups were not identical, the AVS-guided group showed greater improvement in postoperative hypokalemia and greater reduction in the number of antihypertensive medications than the CT-guided group. In addition, for the 75 patients who underwent AVS successfully, the concordance rate between CT abnormalities and AVS lateralization was 60.0% in total, and 22.7% patients changed treatment plans according to the AVS results.

Conclusion: Although the clinical outcomes were not significantly different between the CT-guided and AVS-guided group, the AVS-guided group seemed to benefit more from the surgery, and a considerable number of patients with primary aldosteronism would have received inappropriate treatment if they did not undergo AVS.
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http://dx.doi.org/10.1097/HJH.0000000000002634DOI Listing
February 2021

Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.

J Clin Invest 2020 12;130(12):6278-6289

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China.

BACKGROUNDCurrent methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially in early-stage, minimal, and residual tumors.METHODSWe developed an efficient method, termed utMeMA, for the detection of urine tumor DNA methylation at multiple genomic regions by MassARRAY. We identified the BCa-specific methylation markers by combined analyses of cohorts from Sun Yat-sen Memorial Hospital (SYSMH), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) database. The BCa diagnostic model was built in a retrospective cohort (n = 313) and validated in a multicenter, prospective cohort (n = 175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.RESULTSWe first discovered 26 significant methylation markers of BCa in combined analyses. We built and validated a 2-marker-based diagnostic model that discriminated among patients with BCa with high accuracy (86.7%), sensitivity (90.0%), and specificity (83.1%). Furthermore, the utMeMA-based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage (stage Ta and low-grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%), and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score from this assay was better associated with tumor malignancy and burden.CONCLUSIONUrine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in BCa is a rapid, high-throughput, noninvasive, and promising approach, which may reduce the burden of cystoscopy and blind second surgery.FUNDINGThis study was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
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http://dx.doi.org/10.1172/JCI139597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685755PMC
December 2020

Spermatogenesis of Male Patients with Congenital Hypogonadotropic Hypogonadism Receiving Pulsatile Gonadotropin-Releasing Hormone Therapy Gonadotropin Therapy: A Systematic Review and Meta-Analysis.

World J Mens Health 2020 Jul 14. Epub 2020 Jul 14.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Purpose: Pulsatile gonadotropin-releasing hormone (GnRH) therapy and gonadotropin therapy (GT) were widely used for male patients with congenital hypogonadotropic hypogonadism (CHH), but their efficacy was not well compared before. We conducted this meta-analysis to compare the efficacy of restoring fertility using these two therapies.

Materials And Methods: PubMed, Web of Science, and Scopus were systematically searched for comparative studies evaluating the efficiency of GnRH therapy and GT for male patients with CHH. For continuous outcomes, the weighted mean difference (WMD) was used to measure the difference, whereas the risk ratio with 95% confidence interval was calculated for binary variables.

Results: Overall, eight articles from seven studies with 420 patients enrolled were included in the analysis. Patients from the two different groups were determined to be comparable in age, proportion with Kallmann syndrome, percentage of cryptorchidism and pretreatment hormones (follicular-stimulating hormone, luteinizing hormone, and testosterone). GnRH therapy was related to a larger testicular volume (standardized mean difference=-1.43; p=0.01) and earlier spermatogenesis (WMD=-5.30 months; p=0.004) compared to GT. However, the difference in the rate of positive sperm detection (p=0.08), sperm concentration (p=0.37), and pregnancy rate (p=0.11) were not significant. Allergic reactions mostly occurred during GnRH therapy, while GT was related to a higher incidence of gynecomastia and acne.

Conclusions: Compared to GT, GnRH was related to earlier spermatogenesis and less estradiol-related adverse reactions, although there were no significant differences in spermatogenesis rate, sperm concentration, and pregnancy rate. High-quality randomized controlled trials are needed for future research.
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http://dx.doi.org/10.5534/wjmh.200043DOI Listing
July 2020
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