Association between leucocyte telomere length and erectile dysfunction in US adults: a secondary study based on 2001-2002 NHANES data.

OBJECTIVE: We aimed to explore the association between the leucocyte telomere length (LTL) and erectile dysfunction (ED) among a nationally representative sample of US adults. DESIGN: Secondary population-based study. SETTING: The National Health and Nutrition Examination Survey (NHANES) (2001-2002). PARTICIPANTS: A total of 1694 male participants were extracted from the NHANES database for 2001-2002. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary focus of the study was to determine the association between the LTL and ED, using multivariate logistic regression and restricted cubic spline models for examination. The secondary outcome measures involved conducting stratified subgroup analyses to exclude interactions of different variables with the LTL. RESULTS: Participants with ED had shorter LTLs than those without ED (p<0.05). After adjusting for confounding factors, compared with the reference lowest LTL quartile, the ORs and 95% CIs for the second, third and fourth LTL quartiles were (OR 1.51; 95% CI 1.01 to 2.26), (OR 1.79; 95% CI 1.24 to 2.58) and (OR 1.25; 95% CI 0.74 to 2.11), respectively. In addition, restricted cubic splines showed an inverted J-curve relationship between the LTL and ED. At an LTL of 1.037, the curve showed an inflection point. The ORs (95% CI) of ED on the left and right sides of the inflection point were (OR 1.99; 95% CI 0.39 to 10.20; p=0.385) and (OR 0.17; 95% CI 0.03 to 0.90; p=0.039). CONCLUSION: Our results demonstrated an inverted J-curve relationship between the LTL and ED. When the LTL was ≥1.037, the incidence of ED decreased with increasing LTL.

An Analysis of the Efficacy of Multilayered Repair and Reconstruction Using Combined Tissue Pedicle Flaps for Abdominal Wall Defects in Adult Bladder Exstrophy Patients.

OBJECTIVE: In this study, we conducted a retrospective analysis of cases involving adult classic bladder exstrophy (CBE) accompanied by the absence of the abdominal wall. Specifically, we focused on the utilization of multilayer flaps for reconstructive purposes. In addition, we aimed to share our clinical treatment experience pertaining to similar challenges, thereby providing valuable insights to complement the surgical management of this rare disease. METHODS: We conducted a retrospective analysis of 12 adult patients diagnosed with CBE who underwent initial treatment between June 2013 and January 2020. All patients underwent multilayer reconstruction to address their abdominal wall defects. This involved utilizing shallow flaps derived from the superficial fascia of the abdomen and incorporating myofascial flaps composed of the anterior sheath of the rectus abdominis and aponeurosis of the external oblique muscle. The flap sizes ranged from 9 × 11 cm to 13 × 15 cm. RESULTS: Abdominal wall reconstruction in the 12 patients with CBE resulted in an absence of wound dehiscence recurrence, urinary obstruction, or urinary tract infection. All patients expressed satisfaction with the aesthetic outcome of their abdominal wall based on self-evaluation. They reported a successful resumption of normal life and work activities without experiencing any restrictions. The married patients expressed contentment with their sexual function. CONCLUSION: The utilization of a multilayered reconstruction technique involving multiple flaps in adults with congenital CBE allows for successful restoration of urinary function, as well as the attainment of sufficient abdominal wall strength to support daily life and work activities, while preserving sexual function. However, it is important to approach the evaluation of surgical outcomes with caution because of the rarity of this condition and the lack of objective assessment measures.

Association between cardiovascular disease and risk of female sexual dysfunction: a systematic review and meta-analysis.

AIMS: Female sexual dysfunction (FSD) is a considerably underestimated condition. It has been repeatedly reported that patients with cardiovascular diseases (CVD) may suffer from an increased risk of FSD. However, there is still a lack of comprehensive and systematic evaluation of various CVD and FSD. We aimed to elucidate the association between CVD and FSD through a comprehensive literature review and meta-analysis. METHODS AND RESULTS: The PubMed, Scopus, Embase, and Cochrane Library databases were systematically searched from inception to 28 February 2023. We identified all relevant studies reporting the risk of FSD in subjects with or without CVD. The associations between CVD and the risk of FSD were assessed by calculating pooled odds ratios (ORs) (cross-sectional studies) and risk ratios (RRs) (longitudinal studies) with 95% CIs. We employed random-effects models to account for potential heterogeneity, and the quality of the included studies was assessed using the Newcastle-Ottawa Scale. Fifty-four articles with 148 946 individuals were included in our meta-analysis. Compared with control subjects, subjects with CVD had a 1.51-fold increased risk of FSD (OR 1.51 95% CI, 1.34-1.69, P < 0.001, heterogeneity I2 = 91.4%, P < 0.001). Subgroup analyses indicated that the association between CVD and FSD remained significant in longitudinal studies (RR 1.50 95% CI, 1.21-1.86, P < 0.001, heterogeneity I2 = 86.7%, P < 0.001). Particularly, hypertension (OR 1.41 95% CI, 1.23-1.62, P < 0.001, heterogeneity I2 = 82.7%, P < 0.001), stroke (OR 1.81 95% CI, 1.54-2.12, P < 0.001, heterogeneity I2 = 0%, P < 0.423), and myocardial infarction (OR 2.07 95% CI, 1.60-2.67, P < 0.001 heterogeneity I2 = 82.4%, P < 0.001) were significantly associated with FSD. Meta-regression revealed that the primary sources of heterogeneity in FSD are attributable to adjustments for covariates, study design, and study population. CONCLUSION: Our meta-analysis indicated that patients with CVD suffer from a greater risk of developing FSD. Meanwhile, we validated these findings in longitudinal queues. Notably, conditions such as hypertension, stroke, and myocardial infarction demonstrated a significant association with the incidence of FSD.

Our study provides a significant advantage as the most comprehensive systematic analysis to date. It encompassed 45 cross-sectional and 11 longitudinal studies with 148 946 patients, aiming to investigate the relationship between various types of cardiovascular diseases (CVD) and female sexual dysfunction (FSD). Subgroup analyses were conducted to explore the impact of factors such as region and publication time.Accumulating evidence strongly supports a significant link between CVD and an increased risk of FSD, especially in cases of hypertension, stroke, and myocardial infarction. These findings indicate that more attention should be paid to women's sexual health, particularly in the presence of CVD.Future studies are warranted to investigate the effects of pharmacological interventions on the sexual function of women affected by CVD.

Causal associations between prostate diseases, renal diseases, renal function, and erectile dysfunction risk: a 2-sample Mendelian randomization study.

Background: Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. Aim: The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. Methods: In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran's Q statistic was employed to measure heterogeneity. Outcomes: We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Results: Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. Clinical Implications: The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. Strengths and Limitations: This study's strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. Conclusion: The results of this study suggest a potential link between PCa and a higher risk of ED.

Prognosis of 233 advanced renal cell carcinoma patients in Urumqi: a two-center study / 现代泌尿外科杂志

【Objective】 To investigate the clinical features, treatment methods and prognosis of advanced renal cell carcinoma (RCC) patients in Xinjiang, especially the Han population. 【Methods】 Clinical data of 233 patients with advanced RCC treated in The First Affiliated Hospital and The Affiliated Cancer Hospital of Xinjiang Medical University were retrospectively analyzed, including 133 Han patients.The median age of patients was 52 years (range: 23 to 87), and the maximum tumor diameter was (7.73±4.04) cm.Survival curves were plotted using the Kaplan-Meier method.Multivariate and univariate Cox regression analysis were conducted for all patients, and further analysis was performed for the Han patients. 【Results】 Among the 233 patients, 131 died during the average follow-up of 27.6 months (range: 1 to 120), and the median survival time was 12 months.In this cohort, 110 patients had lymph node metastasis, and 200 had distant metastasis, among them, 21 (10.5%) patients had brain metastasis and 45 (22.5%) patients had adrenal metastasis.The 1-, 3-, and 5-year survival rate were 48.9%, 18.3% and 6.1%, respectively.Univariate analysis revealed that International mRCC Database Consortium (IMDC) score, pathological type, lymph node metastasis, distant metastasis, number of metastatic foci and treatment methods impacted the prognosis in Xinjian (P<0.05).Multivariate analysis indicated that IMDC score, pathological type and distant metastasis were significant factors influencing the prognosis, which were also the prognostic factors of the Han patients (P<0.05). 【Conclusion】 In Xinjiang, patients with advanced renal cell carcinoma have a 6.1% 5-year survival rate and a median survival time of 12 months.Brain and adrenal metastases are common.Prognostic factors include IMDC score, pathological type, and distant metastasis for all patients, including the Han patients.

The relationship between sleep disorders, quality, and duration and sexual dysfunction: a systematic review and meta-analysis.

BACKGROUND: The associations between sexual dysfunction (SD) and sleep disorders, sleep quality, and sleep duration remain unclear. AIM: To assess the relationship between sleep and SD through a literature review and meta-analysis. METHODS: The PubMed, Scopus, Embase, Ovid MEDLINE, and Cochrane Library databases were systematically searched from inception to November 10, 2022. OUTCOMES: Pooled relative risks and 95% CIs were used to examine the association of sleep disorders with SD in longitudinal studies. Pooled odds ratios (ORs) and 95% CIs were used to examine the associations between SD and sleep disorders, sleep quality, and sleep duration in cross-sectional studies. RESULTS: Forty-three articles, including 11 longitudinal studies and 32 cross-sectional studies, were included in the quantitative analysis. The pooled relative risk of SD in patients with sleep disorders was 1.97 in longitudinal studies (95% CI, 1.46-2.67, P < .001; heterogeneity: I2 = 95.0%, P < .001), while the pooled OR of SD in patients with sleep disorders was 2.05 in cross-sectional studies (95% CI, 1.76-2.39, P < .001; heterogeneity: I2 = 91.4%, P < .001). When compared with controls, subjects with poor sleep quality had a 1.49-fold increased risk of SD (OR, 1.49; 95% CI, 1.31-1.71, P < .001; heterogeneity: I2 = 73.4%, P < .001). In addition, short sleep duration was associated with the risk of SD (OR, 1.14; 95% CI, 1.06-1.22, P < .001; heterogeneity: I2 = 0.0%, P = .849). CLINICAL IMPLICATIONS: The risk of SD is significantly increased in patients with sleep disorders and poor sleep quality, indicating that clinicians should monitor sleep among patients with SD. STRENGTHS AND LIMITATIONS: This study is the most comprehensive meta-analysis of the association between sleep and SD to date. However, different sleep disorders may have varying associations with sleep duration and sleep quality; thus, we could not identify the independent effects across the studies. CONCLUSION: Our systematic review and meta-analysis results suggest that sleep disorders, especially obstructive sleep apnea, increase the risk of SD in men and women. Poor sleep quality is significantly associated with SD. Short sleep duration is associated with an increased risk of SD.

FTO-stabilized miR-139-5p targets ZNF217 to suppress prostate cancer cell malignancies by inactivating the PI3K/Akt/mTOR signal pathway.

As one of the most important demethylases for RNA N6-methyladenosine (m6A) modifications, fat mass and obesity-associated protein (FTO) plays anti-cancer role during prostate cancer (PC), but it is still unclear the detailed molecular mechanisms. Here, this study verified that FTO inactivated the tumor-accelerating PI3K/Akt/mTOR pathway to hamper PC development through regulating the downstream miR-139-5p/zinc finger protein 217 (ZNF217) axis. Through performing clinical analysis, it was revealed that FTO was apparently ablated in the cancerous tissues compared to the normal tissues collected from PC patients, and patients with high-expressed FTO predicted a favorable prognosis. Functional experiments confirmed that overexpression of FTO suppressed cell proliferation, mitosis, epithelial-mesenchymal transition (EMT), tumorigenesis and lung metastasis both in vitro and in vivo. The following mechanical experiments verified that FTO stabilized miR-139-5p to increase its expression levels in a m6A-dependent manner, and elevated miR-139-5p induced degradation of ZNF217 through binding to ZNF217 mRNA, resulting in the inactivation of the PI3K/Akt/mTOR signal pathway. Finally, our rescuing experiments confirmed that overexpressed FTO-induced tumor-suppressing effects on PC cells were abrogated by miR-139-5p ablation and ZNF217 overexpression. Collectively, this study firstly validated that FTO exerted its anti-tumor effects in PC through regulating the miR-139-5p/ZNF217 axis in a m6A-dependent manner, providing novel biomarkers for the advancement of anti-cancer agents for PC treatment.

The association between sexual dysfunction and prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Whether there is a connection between sexual dysfunction (SD) and prostate cancer (PCa) is controversial. AIM: We sought to review the interrelationship between SD and PCa and to determine whether there is a definitive risk of men developing PCa after suffering from SD. METHODS: A complete search of the PubMed, Web of Science, Ovid MEDLINE, Embase, and Cochrane Library databases was performed to search for eligible studies published up to October 2022. The protocol for this meta-analysis is available from PROSPERO (ID: CRD42022342381). OUTCOMES: The associations between SD and the risk of PCa were assessed by calculating pooled ORs with 95% CIs, and the standard mean difference (SMD) and its 95% CI were used to assess the relationship between SD and prostate-specific antigen (PSA) levels or prostate volume (PV). Random-effects models were used to account for potential heterogeneity, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. RESULTS: Twenty studies involving 215,626 individuals were included in our meta-analysis. Compared with controls, subjects with SD had a 1.62-fold increased risk of PCa (OR = 1.62, 95% CI, 1.77-2.23, P = .003; heterogeneity: I2 = 97.8%, P < .001). Patients with SD had higher PSA levels than controls (SMD =0.07, 95% CI, 0.00 to 0.13, P = .041; heterogeneity: I2 = 55.6%, P = .027). However, there was no association between SD and PV (SMD = 0.03, 95% CI, -0.05 to 0.11, P = .122; heterogeneity: I2 = 48.5%, P = .100). CLINICAL IMPLICATIONS: Current evidence confirms a potential link between SD and the risk of PCa and that SD in PCa patients should be of concern to clinicians. STRENGTHS AND LIMITATIONS: The strength of this study is that it is to our knowledge the first meta-analysis of studies on the risk of PCa in men with SD. A limitation is that most of the studies included in this meta-analysis focused on ED. CONCLUSION: Our systematic review and meta-analysis results suggest that men with SD have a higher risk of PCa and higher PSA levels than men without SD. However, this is merely inferential, and causality cannot be determined based on the current data. Further longitudinal studies should be performed to validate our preliminary findings.

Mortality relevant factors of COVID-19 infection in kidney transplantation recipients: a systematic review and Meta-analysis / 中华器官移植杂志

Objective:To assess the evidence for relevant factors associated with mortality in COVID-19 kidney transplantation recipients(KTR) through Meta-analysis.Methods:A complete search of PubMed, Web of Science, Medline, Scopus, Cochrane Library, CNKI and Wanfang Database were performed to search for eligible studies on 18 August 2022.Results:twenty-nine studies involving 7 978 Cases were included in our Meta-analysis.Patients with mean age ≥60 years( OR=1.09, 95% CI: 1.06-1.13), Comorbidities including diabetes mellitus( OR=1.49, 95% CI: 1.26-1.76), cardiovascular disease( OR=1.88, 95% CI: 1.33-2.65), and acute kidney injury( OR=3.46, 95% CI: 1.35-8.89) significantly increased mortality risk.KTR with dyspnea ( OR=2.17, 95% CI: 1.38-3.42), higher Hemoglobin ( OR=1.09, 95% CI: 1.00-1.19), Use of mycophenolic ( OR=1.18, 95% CI: 1.02-1.37) and Antibiotics( OR=7.26, 95% CI: 2.11-25.07) at presentation were at higher mortality risk, while diarrhea( OR=0.57, 95% CI: 0.34-0.96) and higher eGFR( OR=0.95, 95% CI: 0.92-0.98) decreased the risk.Overall in-hospital mortality in COVID-19 KTR was 19%, 95% CI: 15%-23%. Conclusions:Our systematic review and -analysis results suggest that overall in-hospital mortality in COVID-19 KTR declined progressively over time.KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.

Alternative splicing patterns reveal prognostic indicator in muscle-invasive bladder cancer.

BACKGROUND: Bladder cancer is one of the most lethal malignancy in urological system, and 20-25% of bladder cancer patients are muscle invasive with unfavorable prognosis. However, the role of alternative splicing (AS) in muscle-invasive bladder cancer (MIBC) remains to be elucidated. METHODS: Percent spliced in (PSI) data obtained from the Cancer Genome Atlas (TCGA) SpliceSeq database (n = 394) were utilized to evaluate the AS events in MIBC. Prognosis-associated AS events were screened out by univariate Cox regression. LASSO Cox regression was used to identify reliable prognostic patterns in a training set and further validated in a test set. Splicing regulatory networks were constructed by correlations between PSI of AS events and RNA expression of splicing factors. RESULTS: As a result, a total of 2589 prognosis-related AS events in MIBC were identified. Pathways of spliceosomal complex (FDR = 0.017), DNA-directed RNA polymerase II, core complex (FDR = 0.032), and base excision repair (FDR = 0.038) were observed to be significantly enriched. Additionally, we noticed that most of the prognosis-related AS events were favorable factors. According to the LASSO and multivariate Cox regression analyses, 15-AS-based signature was established with the area under curve (AUC) of 0.709, 0.823, and 0.857 at 1-, 3-, and 5- years, respectively. The MIBC patients were further divided into high- and low-risk groups based on median risk sores. Interestingly, we observed that the prevalence of FGFR3 with mutations and focal amplification was significantly higher in low-risk group. Functional and immune infiltration analysis suggested potential signaling pathways and distinct immune states between these two groups. Moreover, splicing correlation network displayed a regulatory mode of prognostic splicing factors (SF) in MIBC patients. CONCLUSIONS: This study not only provided novel insights into deciphering the possible mechanism of tumorgenesis and pathogenesis but also help refine risk stratification systems and potential treatment of decision-making for MIBC.

Circular RNA UBAP2 promotes the proliferation of prostate cancer cells via the miR-1244/MAP3K2 axis.

Prostate cancer (PCa) is a common male malignant disease with a high incidence, which can seriously affect the quality of life of patients. The survival rate of patients with PCa has improved to 98.6%; however, new insights for the molecular mechanism are still urgently required. Circular RNA (circ)UBAP2 is a tumor-associated circRNA that has been demonstrated to promote the progression of various types of cancer. CircUBAP2 has been demonstrated to be significantly upregulated in PCa, but its role in the progression of PCa remains unclear. The present study aimed to provide an improved understanding of the regulatory mechanism of circUBAP2 in PCa. circUBAP2 expression was identified to be upregulated in four PCa cell lines and clinical tissues by using reverse transcription-quantitative PCR analysis. Binding sites analysis and luciferase reporter gene assay indicated that the microRNA(miR)-1244/MAP3K2 axis was the target of circUBAP2. Gain-of-function assays revealed that circUBAP2 promoted the proliferation of PCa cells by sponging miR-1244 and promoting the MAP3K2 axis. The present findings may be essential for providing new strategies in the diagnosis and targeted therapy of PCa.

miR-106a-5p Functions as a Tumor Suppressor by Targeting VEGFA in Renal Cell Carcinoma.

MicroRNAs (miRNAs) regulate progression of different cancers. Nevertheless, there is limited information regarding the role of miR-106a-5p in renal cell carcinoma (RCC). Herein, we demonstrate that miR-106a-5p levels are drastically decreased in clear cell RCC (ccRCC) tissues and cell lines, which subsequently contribute to a poor patient overall survival and a high tumor stage. By screening and analyzing, we found that miR-106a-5p directly targets the 3'-UTR of the VEGFA mRNA and led to a decrease in VEGFA. This process is important for tumor cells' growth and colony formation, and overexpression of miR-106a-5p can especially kill kidney tumor cells. Therefore, our data reveal that miR-106a-5p functions as a tumor suppressor by regulating VEGFA and ccRCC may be susceptible to miR-106a-5p therapy.

Up-regulation of DRAM2 promotes tolerance of bladder transitional cell carcinoma to gemcitabine.

INTRODUCTION: Bladder transitional cell carcinoma (BTCC) is one of the most prevalent human malignant diseases. Gemcitabine is commonly applied in the treatment of BTCC while acquired gemcitabine resistance has caused a severe impediment to recovery. This study aimed to investigate the function of DRAM2 in regulating gemcitabine resistance of BTCC. MATERIAL AND METHODS: GSE77883 was introduced to screen out the differentially expressed autophagy-related genes in T24 cells and gemcitabine-resistant T24-GEM cells. After establishing T24-GEM cells ourselves, aberrant expression of DRAM2 was detected by qRT-PCR and Western blot. After stably manipulating the expression of DRAM2 in T24 and T24-GEM cells, the changes of cell biological functions under gemcitabine treatment were compared, including cell viability, apoptosis and autophagy, using colony formation, flow cytometry and electron microscopy respectively. RESULTS: DRAM2 was up-regulated in gemcitabine-resistant T24-GEM cells. Silencing of DRAM2 in T24-GEM cells inhibited the cell autophagy induced by treatment with gemcitabine and contributed to attenuated gemcitabine resistance. Also, overexpression of DRAM2 in T24 cells enhanced the autophagy, strengthened the chemoresistance and decreased the cell apoptosis rate under the treatment with gemcitabine. CONCLUSIONS: Our data suggested that downregulation of DRAM2 rescued the sensitivity of T24-GEM cells to gemcitabine, providing an appropriate therapeutic target for BTCC treatment.

MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1.

In this study, we investigated the mechanism of miR-200c-3p and SLC6A1 in regulating cell activity of clear cell renal cell carcinoma (CCRCC). The mRNA and miRNA expressions of tissue specimens were analyzed by CapitalBio Corporation (Beijing, China). The expression of SLC6A1 in CCRCC cells was examined through qRT-PCR and western blot. The migration and invasion ability of 786-O cells was testified by transwell assay after transfected. 786-O cell proliferation ability was detected by MTT assay. Dual luciferase reporter assay verified the association between SLC6A1 and miR-200c-3p. SLC6A1 was high expressed and miR-200c-3p was low expressed in CCRCC tissues and cells. Besides, lower SLC6A1 expression indicated longer survival time and higher survival rate. MiR-200c-3p could directly target at SLC6A1 and reduce its expression. MiR-200c-3p inhibited the proliferation, migration and invasion in 786-O cells by down-regulating SLC6A1 expression. The results suggested that the miR-200c-3p served as a suppressor for CCRCC via down-regulating SLC6A1.

MicroRNA-145 regulates the differentiation of human adipose-derived stem cells to smooth muscle cells via targeting Krüppel-like factor 4.

Understanding the molecular mechanisms underlying human adipose-derived stem cell (hASC) differentiation to smooth muscle may contribute to the development of effective therapies for relevant muscle defects, such as bladder wall and urethral defects. A previous study described the differentiation of hASCs to smooth muscle cells (SMCs) by transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein­4 (BMP4) treatment. The present study investigated whether microRNA-145 (miR­145) may be involved in the process of hASC differentiation. The expression of miR­145 was significantly increased during differentiation of ASCs to SMCs. SMC­specific genes and proteins, including a­smooth muscle actin (α­SMA), smooth muscle protein­22α(SM22α), calponin and myosin heavy chain (SM­MHC) were upregulated by transfection of a miR­145 mimic. By contrast, these factors were downregulated following introduction of antisense oligonucleotides. In addition, Krüppel­like factor 4 (KLF4) levels, which decreased during the differentiation of hASCs, were downregulated when the cells were transfected miR­145 mimics. Futhermore, inhibition of KLF4 by treatment with short­interfering­RNA against KLF4, resulted in increased expression of SMC­specific genes and proteins. In conclusion, the results of the present study demonstrated that by regulating KLF4, miR­145 may be involved in regulating smooth muscle differentiation of ASCs induced by TGF­ß1 and BMP4.

Impact of smoking status and cumulative smoking exposure on tumor recurrence of non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the effect of smoking status, cumulative smoking exposure and smoking cessation on the outcomes of patient with non-muscle-invasive bladder cancer (NMIBC). METHODS: We collected smoking data from 484 patients with NMIBC who were treated with transurethral resection (TUR); smoking status was categorized as (never smokers vs current smokers vs former smokers). Cumulative smoking exposure was categorized as high smoking exposure (cigarette index ≥400) versus low smoking exposure (cigarette index <400). Association with outcomes was examined by multivariable analyses after adjusting for the effects of standard clinicopathologic factors, and the Kaplan-Meier method was used to estimate the effect of smoking status and cumulative smoking exposure on RFS. RESULTS: A total of 168 (34.7 %) patients were never smoker, 121 (25 %) patients were current smokers, and 195 (40.3 %) patients were former smokers. The median follow-up was 25 months. By multivariate analysis, pathological grade (p = 0.013), history of recurrence (p < 0.001), number of tumors (p < 0.001) and size of tumors (p = 0.013) were significantly associated with tumor recurrence; nevertheless, smoking status did not influence tumor recurrence (p = 0.063). Among current and former smokers, cumulative smoking exposure was significantly associated with tumor recurrence (p < 0.001), compared to current smokers, patients with smoking cessation ≥10 years had a lower risk of tumor recurrence [hazard ratio (HR) 0.456, p = 0.007]. CONCLUSIONS: Smoking affects the prognosis of patient with NMIBC, which is still controversial; however, among ever smokers, a high cumulative exposure smoking can significantly increase the risk of tumor recurrence. Quitting smoking might be associated with a lower recurrence rate for patients with NMIBC.

Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma.

OBJECTIVE: microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. METHOD: Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR. RESULT: The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue. CONCLUSION: We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC.

Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is Modulated by CaMKIIγ.

The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is known to participate in maintenance and switches of smooth muscle cell (SMC) phenotypes. However, which isoform of CaMKII is involved in differentiation of adult mesenchymal stem cells into contractile SMCs remains unclear. In the present study, we detected γ isoform of CaMKII in differentiation of human adipose derived stem cells (hASCs) into SMCs that resulted from treatment with TGF-ß1 and BMP4 in combination for 7 days. The results showed that CaMKIIγ increased gradually during differentiation of hASCs as determined by real-time PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIγ decreased the protein levels and transcriptional levels of smooth muscle contractile markers (a-SMA, SM22a, calponin, and SM-MHC), while CaMKIIγ overexpression increases the transcriptional and protein levels of smooth muscle contractile markers. These results suggested that γ isoform of CaMKII plays a significant role in smooth muscle differentiation of hASCs.

Culture and Identification of Mouse Bone Marrow-Derived Dendritic Cells and Their Capability to Induce T Lymphocyte Proliferation.

BACKGROUND: The aim of this study was to establish a culture method for mouse dendritic cells (DCs) in vitro and observe their morphology at different growth stages and their ability to induce the proliferation of T lymphocytes. MATERIAL/METHODS: Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. The derived DCs were then assessed for morphology, phenotype, and function. RESULTS: The mouse BM-derived mononucleocytes had altered cell morphology 3 days after induction by GM-CSF and IL-4 and grew into colonies. Typical dendrites appeared 8 days after induction. Many mature DCs were generated, with typical dendritic morphology observed under scanning electron microscopy. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in the mature DCs. Furthermore, the mature DCs displayed a strong potency in stimulating the proliferation of syngenic or allogenic T lymphocytes. CONCLUSIONS: Mouse BM-derived mononucleocytes cultured in vitro can produce a large number of DCs, as well as immature DCs, in high purity. The described in vitro culture method lays a foundation for further investigations of anti-tumor vaccines.

Circulating miR-106a in serum are potential biomarker for renal cell carcinoma / 中华泌尿外科杂志

Objective To detect the circulating miR-106a levels in serum before and after surgery in patients with renal clear cell carcinoma,and to explore its relationship with clinical-pathological parameters.Methods 30 serum samples from patients with renal clear cell carcinoma were collected before and after surgery during February 2013 to July 2014.This study included 30 normal controls.All serum miR-106a levels were detected using the real-time PCR.Results The serum miR-l06a levels in patients with renal clear cell carcinoma pre-operatively wcre significantly greater than normal controls (Z =-4.251,P =0.0001).The serum miR-106a levels in patients post-operatively had no significant differences compared to normal controls (Z =-0.244,P =0.807).The serum miR-106a levels in post-operative samples were significantly lower than the pre-operative samples (Z =-4.229,P =0.0001).Serum miR-106a levels and other clinical-pathological parameters had no correlation in patients with renal clear cell carcinoma(tumor size:Z =-0.775,P =0.439;Fuhrman grade:Z =-1.694,P =0.090).The receiver operating characteristic curve was used to distinguish pre-operative samples and normal controls,its AUC was 0.819 (95％ CI:0.710-0.929,P =0.0001) with 86.7％ sensitivity and 70.0％ specificity.Conclusions The serum miR-106a levels in patients with renal clear cell carcinoma pre-operatively were significantly greater than post-operatively with no correlation in tumor size and Fuhrman grade.The outcome suggested that serum miR-106a can be regarded as a potential molecular marker in renal clear cell carcinoma.