Exosomes derived from bladder epithelial cells infected with uropathogenic Escherichia coli increase the severity of urinary tract infections (UTIs) by impairing macrophage function.

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs) in humans. Moreover, as one of the most common bacterial pathogens, UPEC imposes a substantial burden on healthcare systems worldwide. Epithelial cells and macrophages are two major components of the innate immune system, which play critical roles in defending the bladder against UPEC invasion. Yet, the routes of communication between these cells during UTI pathogenesis are still not fully understood. In the present study, we investigated the role of membrane-bound nanovesicles (exosomes) in the communication between bladder epithelial cells and macrophages during UPEC infection, using an array of techniques such as flow cytometry, miRNA profiling, RNA sequencing, and western blotting. Moreover, our in vitro findings were validated in a mouse model of UPEC-induced cystitis. We found that UPEC infection induced the bladder epithelial MB49 cell line to secrete large numbers of exosomes (MB49-U-Exo), which were efficiently absorbed by macrophages both in vivo and in vitro. Assimilation of MB49-U-Exo induced macrophages to produce proinflammatory cytokines, including tumor necrosis factor (TNF)α. Exposure of macrophages to MB49-U-Exo reduced their phagocytic activity (by downregulating the expression of phagocytosis-related genes) and increased their rate of apoptosis. Mechanistically, we showed that MB49-U-Exo were enriched in miR-18a-5p, which induced TNFα expression in macrophages by targeting PTEN and activating the MAPK/JNK signaling pathway. Moreover, administration of the exosome secretion inhibitor GW4869 or a TNFα-neutralizing antibody alleviated UPEC-mediated tissue damage in mice with UPEC-induced cystitis by reducing the bacterial burden of the bladder and dampening the associated inflammatory response. Collectively, these findings suggest that MB49-U-Exo regulate macrophage function in a way that exacerbates UPEC-mediated tissue impairment. Thus, targeting exosomal -release or TNFα signaling during UPEC infection may represent promising non-antibiotic strategies for treating UTIs.

A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Transcriptomic insights into UTUC: role of inflammatory fibrosis and potential for personalized treatment.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare disease, belonging to the same category of urothelial cancers as bladder cancer (BC). Despite sharing similar non-surgical treatment modalities, UTUC demonstrates a higher metastasis propensity than BC. Furthermore, although both cancers exhibit similar molecular disease emergence mechanisms, sequencing data reveals some differences. Our study investigates the transcriptomic distinctions between UTUC and BC, explores the causes behind UTUC's heightened metastatic tendency, constructs a model for UTUC metastasis and prognosis, and propose personalized treatment strategies for UTUC. METHODS: In our research, we utilized differential gene expression analysis, interaction networks, and Cox regression to explore the enhanced metastatic propensity of UTUC. We formulated and validated a prognostic risk model using diverse techniques, including cell co-culture, reverse transcription quantitative polymerase chain reaction (rt-qPCR), western blotting, and transwell experiments. Our methodological approach also involved survival analysis, risk model construction, and drug screening leveraging the databases of CTRPv2, PRISM and CMap. We used the Masson staining technique for histological assessments. All statistical evaluations were conducted using R software and GraphPad Prism 9, reinforcing the rigorous and comprehensive nature of our research approach. RESULTS: Screening through inflammatory fibrosis revealed a reduction of extracellular matrix and cell adhesion molecules regulated by proteoglycans in UTUC compared with BC, making UTUC more metastasis-prone. We demonstrated that SDC1, LUM, VEGFA, WNT7B, and TIMP3, are critical in promoting UTUC metastasis. A risk model based on these five molecules can effectively predict the risk of UTUC metastasis and disease-free survival time. Given UTUC's unique molecular mechanisms distinct from BC, we discovered that UTUC patients could better mitigate the issue of poor prognosis associated with UTUC's easy metastasis through tyrosine kinase inhibitors (TKIs) alongside the conventional gemcitabine and cisplatin chemotherapy regimen. CONCLUSIONS: The poor prognosis of UTUC because of its high metastatic propensity is intimately tied to inflammatory fibrosis induced by the accumulation of reactive oxygen species. The biological model constructed using the five molecules SDC1, LUM, VEGFA, WNT7B, and TIMP3 can effectively predict patient prognosis. UTUC patients require specialized treatments in addition to conventional regimens, with TKIs exhibiting significant potential.

Ultrasound-guided renal access and balloon dilation for PCNL in the prone position: results of a multicenter prospective observational study.

PURPOSE: To investigate the safety and efficacy of ultrasound-guided renal access and tract dilation using balloon dilators, as well as to identify suitable patients for this technique. METHODS: Consecutive patients undergoing ultrasound-guided PCNL using balloon dilators between December 2019 and June 2020 in seven large medical centers from China were prospectively enrolled. Demographic and perioperative parameters of the patients were collected. Logistic regression analysis was used to analyze factors that would affect the success rate of tract establishment using ultrasound-guided renal access and balloon dilation. RESULTS: A total of 170 patients were included in this study, among whom, 91.18% of the (155/170) patients had a successful tract establishment under ultrasound guidance on the first attempt. The stone-free rate was 83.5% and postoperative complications occurred in 14 patients (8.23%). In univariate analysis, history of ipsilateral surgery (p = 0.026), and stone diameter (p = 0.01) were significantly associated with tract establishment failure, while a larger width of the target calyx (p = 0.016) and the presence of hydronephrosis (p = 0.001) were significantly associated with a successful tract establishment. In multivariate analysis, only hydronephrosis in target calyx (p = 0.027) was a favorable factor for successful tract establishment, and the history of ipsilateral renal surgery (p = 0.012) was the only independent risk factor for failure of tract establishment. CONCLUSION: It was safe and effective to establish percutaneous renal access with balloon dilation under whole-process ultrasound monitoring during PCNL. Furthermore, patients with a hydronephrotic target calyx and without history of ipsilateral renal surgery were most suited to this technique. Trial registration CHiCTR1800014448.

Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression.

BACKGROUND: Exosomes mediated crosstalk between tumor cells and other stromal cells including tumor associated macrophages plays an essential role in reprogramming tumor microenvironment (TME) to facilitate tumor progression. However, the mechanism of tumor derived exosomes promotes bladder cancer progression have not been defined. METHODS: Exosomes were extracted from bladder cancer cells MB49 conditioned medium by ultracentrifugation. The effects of MB49-derived exosomes on macrophages polarization were analyzed by qPCR, flow cytometry, and Western blot. The immunosuppressive phenotype and function of MB49-derived exosomes stimulated macrophages were verified by tumor xenograft assays and T cell co-culture experiments. Exosomal miRNAs were analyzed by microarray to identify potential targets regulating macrophage polarization. RESULTS: MB49-derived exosomes could be ingested by macrophages, consequently promoting macrophages immunosuppressive polarization. Mechanically, the MB49-derived exosomes induced macrophage M2 polarization was mediated by down-regulation of PTEN and activation of AKT/STAT3/6 signaling. Moreover, hindrance of the generation or secretion of exosomes by GW4869 inhibited macrophages differentiation into immunosuppressive phenotype and function, thereby suppressed tumor growth in a mouse subcutaneous tumor model. CONCLUSION: Our study confirmed the contribution of bladder cancer derived exosomes on the establishment of immunosuppressive TME and provided a potential therapeutic target for bladder cancer treatment. Video Abstract.

LncRNA SNHG1 regulates immune escape of renal cell carcinoma by targeting miR-129-3p to activate STAT3 and PD-L1.

Immune escape of renal cell carcinoma (RCC) impacts patient survival. However, the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in RCC immune escape remains unclear. Quantitative real-time PCR and western blotting results revealed that the expression of lncRNA SNHG1 and STAT3 were upregulated in RCC tissues and cells and that the expression of miR-129-3p was downregulated. Enzyme-linked immunosorbent assay results revealed the increased levels of immune-related factors (interferon-γ, tumour necrosis factor α, and interleukin-2) in RCC tissues. SNHG1 knockdown or miR-129-3p overexpression inhibited the proliferation and invasion of A498 and 786-O cells, while the proliferation and cytotoxicity of CD8+ T cells increased, which promoted the secretion of immune-related factors. STAT3 overexpression decreased the protective effect of miR-129-3p overexpression on RCC cell immune escape. In addition, miR-129-3p knockdown and STAT3 overexpression decreased the protective effect of lncRNA SNHG1 knockdown on RCC cell immune escape. In addition, PD-L1 expression was downregulated after lncRNA SNHG1 knockdown but upregulated after miR-129-3p knockdown and STAT3 overexpression. Dual-luciferase assays showed that lncRNA SNHG1 targets miR-129-3p, and miR-129-3p targets STAT3. RNA pull-down and RNA immunoprecipitation assays verified the regulatory relationship between SNHG1 and STAT3. In vivo, shSNHG1 prolonged the overall survival of RCC tumour model mice and inhibited RCC tumour growth and immune escape but increased CD8+ T cell infiltration in mice. Our findings provide an experimental basis for elucidating the molecular mechanisms of immune escape by RCC and reveal a novel target to treat this disease.

Lasers versus bipolar technology in the transurethral treatment of benign prostatic enlargement: a systematic review and meta-analysis of comparative studies.

PURPOSE: To systematically review studies comparing the overall efficacy and safety of lasers and bipolar technology for the transurethral treatment of benign prostatic enlargement (BPE). METHODS: A systematic review of the literature was completed in February 2018. Studies with comparative data between different lasers and bipolar technologies (enucleation or resection) were included in this review. A meta-analysis was performed using STATA 14.0, and subgroup analyses were also performed regarding the type of laser (holmium, thulium, green light and diode). RESULTS: 27 studies with 31 published articles (4382 patients) were selected for the meta-analysis. Compared with bipolar technology, lasers demonstrated shorter catheterization duration (standardized mean difference (SMD): 1.44; 95% CI 1.07-1.81; p < 0.001) and shorter hospital stay (SMD: 1.16; 95% CI 0.83-1.49; p < 0.001), and a smaller drop in hemoglobin (Hb) level (SMD: 0.86; 95% CI 0.47-1.26; p < 0.001). However, significant heterogeneity was detected in the studies and statistical significance was lost on sub-analyses. Furthermore, there were no significant differences between lasers and bipolar technology in the maximum flow rate (Qmax) and international prostate symptom score (IPSS) at a minimum of 3 months after treatment. Complications, including urethral stricture, urinary incontinence, urinary tract infection, re-catheterization and blood transfusion, did not significantly differ between lasers and bipolar technology. CONCLUSION: Early efficacy and safety profiles were comparable between bipolar and laser treatments. Differences were observed in terms of smaller reduction in Hb, shorter catheterization duration and shorter hospital stay in favor of lasers. However, the smaller reduction in Hb, with lasers, did not translate into reduced transfusion requirements. Furthermore, there was significant heterogeneity in the studies and, in subgroup analyses, the differences were not statistically significant.

MicroRNA-219c-5p regulates bladder fibrosis by targeting FN1.

BACKGROUND: We found that the bladders of multiple sclerosis mice were significantly fibrotic. This study aimed to investigate the relationship between fibronectin 1 (FN1) and bladder fibrosis, as well as the microRNAs involved in FN1 regulation. METHODS: The degree of bladder smooth muscle fibrosis was observed by immunohistochemistry. In addition, we used quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting to determine FN1 expression in bladders with different grades of fibrosis. Bioinformatics analysis revealed that miR-199a-3p, miR-219c-5p and miR-3572-3p could inhibit FN1 synthesis. Therefore, miR-199a-3p, miR-219c-5p and miR-3572-3p were overexpressed or knocked down in bladder smooth muscle cells (BSMCs), and the respective transfection and FN1 knockdown efficiencies were detected by RT-qPCR. Only miR-219c-5p overexpression and knockdown produced the expected results. A dual luciferase reporter assay was used to determine the targeting relationship between miR-219c-5p and FN1. Flow cytometry and Cell Counting Kit 8 (CCK8) experiments confirmed that miR-219c-5p reduced FN1 expression and affected the biological activity of smooth muscle cells. Agomir and anagomir of miR-219c-5p were transfected in vivo to observe the change of bladder fibrosis in mice. RESULTS: With increasing bladder fibrosis, FN1 expression increased, while miR-199a-3p, miR-219c-5p, and miR-3572-3p expression levels decreased. The RT-qPCR results after transfection showed that only miR-219c-5p could regulate FN1. Indeed, the dual luciferase reporter assay results indicated that miR-219c-5p targeted FN1 directly. CCK8 and cell cycle assays showed that miR-219c-5p overexpression inhibited BSMC proliferation, while miR-219c-5p knockdown promoted BSMC proliferation. An apoptosis assay showed that miR-219c-5p overexpression promoted apoptosis, while miR-219c-5p knockdown inhibited BSMC apoptosis. The agomir and anagomir transfected with miR-219c-5p in vivo found that the bladder fibrosis of the mice in the agomir group was reduced, and the anagomir group was worse. CONCLUSIONS: Our findings indicate that FN1 up-regulation and miR-219c-5p down-regulation play an important role in the development of bladder fibrosis, and miR-219c-5p participates in bladder fibrosis by regulating FN1 expression. Thus, a novel antifibrotic function of miR-219c-5p is proposed, which may represent a potential target for the diagnosis and treatment of bladder fibrosis.

Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N6-methyladenosine of Notch1.

BACKGROUND: N6-methyladenosine (m6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year. MATERIALS AND METHODS: There are various cells in bladder tumor bulk, and a small population cells defined as tumor initiating cells (TIC) have self-renewal and differentiation capacities. Bladder TICs drive bladder tumorigenesis and metastasis, and their activities are fine regulated. However, the role of N6-methyladenosine in bladder TIC self-renewal is unknown. RESULTS: Here, we found a decrease of N6-methyladenosine in bladder tumors and bladder TICs. N6-methyladenosine levels are related to clinical severity and outcome. Mettl14 is lowly expressed in bladder cancer and bladder TICs. Mettl14 knockout promotes the proliferation, self-renewal, metastasis and tumor initiating capacity of bladder TICs, and Mettl14 overexpression exerts an opposite role. Mettl14 and m6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal. CONCLUSION: This work reveals a novel role of Mettl14 and N6-methyladenosine in bladder tumorigenesis and bladder TICs, adding new layers for bladder TIC regulation and N6-methyladenosine function.

Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to exert important roles in cancer development and progression. The biological function of lncRNA X-inactive specific transcript (XIST) in the development of renal cell carcinoma (RCC) and the underlying mechanisms are still largely unknown. In this study, we found that XIST was down-regulated in RCC tissues and cells. Overexpression of XIST significantly suppressed cell proliferation and induced cell G0/G1 arrest in vitro and inhibited tumor growth in vivo. We further found that XIST could directly interact with miR-106b-5p and increase the expression of P21. Thus, XIST positively regulated the expression of P21 through sponging miR-106b-5p, and played a tumor suppressor role in RCC. Moreover, we found that curcumin could regulate XIST/miR-106b-5p/P21 axis in RCC cells. Our study exhibits the role of XIST as a miRNA sponge in RCC and supports the potential application of XIST in RCC therapy.

[Clinical characterization of testicular yolk sac tumor in children and adults].

OBJECTIVE: To compare the clinical characteristics of simple testicular yolk sac tumor (YST) in children with those in adults so as to improve the diagnosis and treatment of the malignance. METHODS: This study included 75 cases of simple testicular YST pathologically confirmed between May 2008 and July 2018, which were divided into groups A (aged <18 years, n = 64) and B (aged ≥18 years, n = 11). We analyzed the clinical data on all the cases and compared the clinical manifestations, laboratory results, pathological findings, clinical stages, treatment methods and prognostic outcomes between the two groups of patients. RESULTS: The patients of group A ranged in age from 6 months to 5 years (ï¼»1.38 ± 0.89ï¼½ yr), with the tumor diameter of 0.9－6.0 (2.48 ± 1.12) cm, while those of group B from 25 to 49 years (median 34 years), with the tumor diameter of 3.5－6.3 (5.16 ± 1.32) cm, most presenting with a painless scrotal mass, 4 (6.2%) in group A and 5 (45.5%) in group B with testis pain. There were statistically significant differences between the two groups in the tumor diameter and initial manifestations (P < 0.05). All the patients were treated by radical high-level spermatectomy and orchiectomy and, in addition, 1 in group A and 3 in group B by retroperitoneal lymph node dissection (RPLND), 24 in the former and 5 in the latter group followed by chemotherapy. Elevated levels of serum alpha-fetoprotein (AFP) were observed in all the cases. Sixty-five of the patients were followed up for 10－78 (52.00 ± 23.78) months, during which 2 cases of simple metastasis, 3 cases of simple relapse, 3 cases of relapse with metastasis and 5 cases of death were found in group A, and 5 cases of simple metastasis, 1 case of simple relapse, 1 case of relapse with metastasis and 4 cases of death in group B. CONCLUSIONS: There are significant differences in the clinical manifestation, biological behavior, treatment and prognosis of testicular YST between children and adults. In children, most of the testicular YST cases are at clinical stage I and preferably treated by radical high-level spermatectomy and orchiectomy with favorable prognosis. In adults, however, the tumor is highly malignant, with high incidences of recurrence and metastasis and poor prognosis, for the treatment of which the first choice is radical high-level spermatectomy and orchiectomy combined with RPLND and chemotherapy.

NDRG2 knockdown promotes fibrosis in renal tubular epithelial cells through TGF-ß1/Smad3 pathway.

Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-ß1-induced renal tubular epithelial cells (HK-2). Our results show that TGF-ß1 down-regulates NDRG2 mRNA and protein expression in HK-2 cells. Moreover, NDRG2 knockdown dramatically reduces the TGF-ß1-induced protein and mRNA of E-cadherin and increases the TGF-ß1-induced protein and mRNA expression level of α-SMA, Vimentin, Snail, Col-I, Col-III and FN; this is reversed by NDRG2 overexpression. Furthermore, NDRG2 silencing significantly increases the phosphorylation level of Smad3 (p-Smad3), which is decreased by NDRG2 overexpression, although these have no effect on the protein expression of p-Smad2 and Smad7. In addition, SIS3, a specific inhibitor of Smad3 phosphorylation, partly reverses the effect of NDRG2 knockdown on the protein and mRNA expression of epithelial-mesenchymal transition (EMT) markers and ECM components in TGF-ß1-induced HK-2 cells. Taken together, our results indicate that NDRG2 knockdown promotes renal fibrosis through its effect on the protein and mRNA expression of EMT markers and ECM components by regulating the downstream Smad3 signaling pathway in renal tubular epithelial cells. Modulation of NDRG2 expression might provide a new therapy for renal fibrosis.

Transcription factor ZFP38 is essential for meiosis prophase I in male mice.

The production of haploid gametes by meiosis is a cornerstone of sexual reproduction and maintenance of genome integrity. Zfp38 mRNA is expressed in spermatocytes, indicating that transcription factor ZFP38 has the potential to regulate transcription during meiosis. In this study, we generated Zfp38 conditional knockout mice (Zfp38(flox/flox), Stra8-Cre, hereafter called Zfp38 cKO) and found that spermatogenesis did not progress beyond meiosis prophase I in Zfp38 cKO mice. Using a chromosomal spread technique, we observed that Zfp38 cKO spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3 double staining. Progression of DNA double-strand breaks (DSB) repair is disrupted in Zfp38 cKO spermatocytes, as revealed by γ-H2AX, RAD51 and MLH1 staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51, TEX15 and PALB2, were significantly reduced in Zfp38 cKO spermatocytes. Taken together, our data suggest that ZFP38 is critical for the chromosomal synapsis and DSB repairs partially via its regulation of DSB repair-associated protein expression during meiotic progression in mouse.

Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible.

Restless legs syndrome and hypertension in Chinese pregnant women.

Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS.

Restless legs syndrome among pregnant women in China: prevalence and risk factors.

BACKGROUND: The goal of this study was to identify the prevalence and clinical correlates and severity of restless legs syndrome (RLS) among pregnant women in mainland China. METHODS: This cross-sectional study enrolled 1584 women (18-40 years old) who came to a prenatal outpatient clinic to consult an obstetrician. Pregnant women were studied in each trimester, and assessments included interviews about RLS symptoms and related questions. Standardized questionnaires include the International Restless Syndrome Scale and the Pittsburgh Sleep Quality Questionnaire. Blood tests included levels of hemoglobin and mean corpuscular volume. RESULTS: RLS was diagnosed in 177 of 1584 women (11.2%); 4.2% were categorized as having pre-existing RLS and 54.8% reported onset of RLS symptoms after the 24th week. Multivariate analysis revealed that anemia was positively correlated with RLS. For the participants who first experienced RLS in pregnancy, RLS severity in the third trimester was more severe when compared with the first and second trimesters. Sleep disorders occurred more frequently in the third trimester. CONCLUSIONS: In our study, RLS was frequent in pregnant Chinese women, and anemia was identified as an independent predictor of the disease. Further, most participants reported their symptoms during the third trimester, and the severity of RLS and sleep disorders of participants was more prominent in the third trimester.

Introducing the Quill™ device for modified sleeve circumcision with subcutaneous suture: a retrospective study of 70 cases.

OBJECTIVE: The purpose of the study was to evaluate the safety and feasibility of treatment for male circumcision using modified sleeve circumcision and subcuticular suture with the Quill™ device. METHODS: From May 2011 to March 2012, 70 consecutive cases of male circumcision were performed using an alternative technique with the Quill™ device by a single surgeon in our institution. The inclusion and exclusion criteria for the selection process of this procedure were the same as for conventional circumcision. We evaluated the indications and perioperative outcomes. The circumcisions were performed as day-case procedures under local anesthesia. RESULTS: All patients were followed up for a minimum of 3-6 months. The ages ranged from 8 to 68 (mean = 27.0 years, SD = 10). The indications for surgery were either cosmetic (n = 16, 22.9%) or medical [redundant prepuce (n = 36, 51.4%), phimosis (n = 5, 7.1%), paraphimosis (n = 2, 2.9%), balanoposthitis (n = 9, 12.9%), melanoma (n = 1, 1.4%), and condyloma acuminata (n = 1, 1.4%)] (n = 54, 77.1%). The mean operation time in this group was 29 min (19-38 min) when the Quill™ device was used. In all, 3 cases developed complications (4.3%). The final cosmetic result was satisfactory for both the patients and their spouses or parents. CONCLUSION: This study showed that modified sleeve circumcision and subcuticular suture were safe and reliable surgical methods of circumcision that provide a better cosmetic result.

Over-expression of testis-specific expressed gene 1 attenuates the proliferation and induces apoptosis of GC-1spg cells.

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.

Bibliometric and Visualization Analysis of Stem Cell Therapy for Erectile Dysfunction.

Purpose: As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field. Methods: Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis. Results: A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation. Conclusion: The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.