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PURPOSE: Cumulative studies have shown that vitamin D may be associated with lower urinary tract symptoms but the findings have been inconsistent. The aim of this study was to systematically evaluate the relationship between vitamin D and lower urinary tract symptoms. MATERIALS AND METHODS: The PubMed®, Scopus® and Embase™ databases were searched for articles up to June 2020. A meta-analysis was conducted to evaluate the effects of vitamin D insufficiency or intake on lower urinary tract symptoms. A qualitative description summarized vitamin D intervention for treating lower urinary tract symptoms. Sensitivity analysis was conducted to examine heterogeneity and the robustness of the results. RESULTS: A total of 23 studies including 86,332 participants were analyzed in our study. Vitamin D insufficiency was associated with a 1.37-fold to 2.06-fold increased likelihood of having lower urinary tract symptoms, and patients with lower urinary tract symptoms had significantly lower levels of vitamin D. Furthermore, vitamin D intake was significantly associated with an 11% reduction in the risk of lower urinary tract symptoms. In the subgroup analysis, the effects of vitamin D insufficiency on the risk of lower urinary tract symptoms were notably observed in nonAsians, females and patients with urinary incontinence. CONCLUSIONS: Consistent results indicated that vitamin D insufficiency was a crucial risk factor for lower urinary tract symptoms and that vitamin D supplementation showed promising effects on these symptoms. It would be of great guiding significance to consider vitamin D status when treating lower urinary tract symptoms.
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Sintomas do Trato Urinário Inferior/complicações , Deficiência de Vitamina D/complicações , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Fatores de Risco , Vitamina DRESUMO
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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Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/metabolismo , Exossomos/metabolismo , Miócitos de Músculo Liso/metabolismo , Ereção Peniana/fisiologia , Adipócitos/citologia , Animais , GMP Cíclico/metabolismo , Diabetes Mellitus Experimental/terapia , Disfunção Erétil/terapia , Fibrose , Masculino , Microscopia Confocal , Óxido Nítrico/metabolismo , Pênis/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Células-Tronco/citologiaRESUMO
STUDY QUESTION: Can a counselling tool be developed for couples with different types of azoospermia to predict the probability of clinical pregnancy in ICSI after surgical sperm retrieval? SUMMARY ANSWER: A prediction model for clinical pregnancy in ICSI after surgical sperm retrieval in different types of azoospermia was created and clinical type of azoospermia, testicular size, male FSH, male LH, male testosterone, female age, female antral follicle count (AFC) and female anti-Müllerian hormone (AMH) were used as predictors. WHAT IS KNOWN ALREADY: Prediction models are used frequently to predict treatment success in reproductive medicine; however, there are few prediction models only for azoospermia couples who intend to conceive through surgical sperm retrieval and ICSI. Furthermore, no specific clinical types of azoospermia have been reported as predictors. STUDY DESIGN, SIZE, DURATION: A cohort study of 453 couples undergoing ICSI was conducted between 2016 and 2019 in an academic teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing ICSI with surgically retrieved sperm were included, with 302 couples included in the development set and 151 couples included in the validation set. We constructed a prediction model using multivariable logistic regression analysis. The internal validation was based on discrimination and calibration. MAIN RESULTS AND THE ROLE OF CHANCE: We found that for male patients involved in our model, different clinical types of azoospermia are associated with different clinical pregnancy outcomes after ICSI. Considering the clinical type of azoospermia, larger testicular volume and higher levels of FSH, LH and testosterone in the body are associated with higher clinical pregnancy success rates. For women involved in our model, younger age and higher AFC and AMH levels are associated with higher clinical pregnancy success rates. In the development set, the AUC was 0.891 (95% CI 0.849-0.934), indicating that the model had good discrimination. The slope of the calibration plot was 1.020 (95% CI 0.899-1.142) and the intercept of the calibration plot was -0.015 (95% CI -0.112 to 0.082), indicating that the model was well-calibrated. From the validation set, the model had good discriminative capacity (AUC 0.866, 95% CI 0.808-0.924) and calibrated well, with a slope of 1.015 (95% CI 0.790-1.239) and an intercept of -0.014 (95% CI -0.180 to 0.152) in the calibration plot. LIMITATIONS, REASONS FOR CAUTION: We found that BMI was not an effective indicator for predicting clinical pregnancy, which was inconsistent with some other studies. We lacked data about the predictors that reflected sperm characteristics, therefore, we included the clinical type of azoospermia instead as a predictor because it is related to sperm quality. We found that almost all patients did not have regular alcohol consumption, so we did not use alcohol consumption as a possible predictor, because of insufficient data on drinking habits. We acknowledge that our development set might not be a perfect representation of the population, although this is a common limitation that researchers often encounter when developing prediction models. The number of non-obstructive azoospermia patients that we could include in the analysis was limited due to the success rate of surgical sperm retrieval, although this did not affect the establishment and validation of our model. Finally, this prediction model was developed in a single centre. Although our model was validated in an independent dataset from our centre, validation for different clinical populations belonging to other centres is required before it can be exported. WIDER IMPLICATIONS OF THE FINDINGS: This model enables the differentiation between couples with a low or high chance of reaching a clinical pregnancy through ICSI after surgical sperm retrieval. As such it can provide couples dealing with azoospermia a new approach to help them choose between surgical sperm retrieval with ICSI and the use of donor sperm. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the National Natural Science Foundations of China (81501246 and 81501020 and 81671443). The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Azoospermia , Recuperação Espermática , Azoospermia/terapia , China , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma IntracitoplásmicasRESUMO
OBJECTIVE: To compare a new method "one-glass test" with the international gold standard "four-glass test" for the classification of chronic prostatitis (CP). METHODS: Totally, 360 CP patients were randomly assigned to receive "one-glass test" (n = 240) and "four-glass test" (n = 120) for the classification of the disease. Urine and expressed prostatic secretion (EPS) samples were collected from all the patients for microscopic and bacteriological examination and the results were subjected to statistical analysis, followed by comparison of the safety, procedures and costs of the two strategies. RESULTS: Compared with the "four-glass test", the urethal membrane "one-glass test" showed a significantly higher accuracy in the classification of types â ¡ (8.6%), â ¢A (50.0%) and â ¢B prostatitis (41.4%) (P < 0.05), simpler procedures and lower costs, reducing RMB ¥412 (61.24%) per case. CONCLUSIONS: The "one-glass test" has a high accuracy in the diagnosis and classification of chronic prostatitis and the advantages of simple operation and low cost, and therefore can be used in place of the "four-glass test" and widely promoted clinically.
Assuntos
Líquidos Corporais , Prostatite , Doença Crônica , Humanos , Masculino , Próstata , Prostatite/diagnósticoRESUMO
BACKGROUND: Oxidative stress is a significant contributor to the poor treatment efficacy on erectile dysfunction induced by diabetes mellitus (DMED). Thus, understanding the mechanism underlying oxidative stress will aid in the identification of novel therapeutic targets. AIM: To define the role of Janus kinase 2 (JAK2) in mediating oxidative stress in the corpus cavernosum smooth muscle cells (CCSMCs) and to investigate the therapeutic effect of monomeric berberine (BB), which inhibits JAK2, in the pathogenesis of DMED. METHODS: Streptozotocin was used to establish type I diabetic rat models and apomorphine tests were conducted to determine DMED rats. Eighteen DMED rats were divided into the DMED group and the DMED+BB group, whereas another 10 age-matched rats formed the control group. CCSMCs were isolated from the corpus cavernosum of rats and were treated with the JAK2 inhibitor alpha cyanano-(3,4-hydroxyl)N-benzophenylamine (AG490) and/or BB. OUTCOMES: Metabolic parameters; erectile function; histologic and molecular alterations. RESULTS: Erectile function was impaired and excessive oxidative stress was found in the DMED group. Excessive oxidative stress led to decreased expression level of phosphorylated endothelial nitric oxide synthase at serine 1177/endothelial nitric oxide synthase and increased expression level of Ras homolog gene family and Rho kinase 1/2. Meanwhile, the relative expression ratio of phosphorylated JAK2/JAK2 was significantly greater in the DMED group than that in the other groups. In vitro, oxidative stress was significantly reduced along with reduced intracellular calcium upon treatment with the JAK2 inhibitor, AG490. Moreover, the CCSMCs treated with BB showed changes similar to those upon treatment with AG490. In vivo experiments also confirmed that the erectile function of the DMED+BB group was improved, accompanied by decreased phosphorylated JAK2/JAK2 and decreased oxidative stress. CLINICAL TRANSLATION: JAK2 can be used as a therapeutic target and BB can be used as a potential drug for the clinical treatment of DMED. STRENGTHS AND LIMITATIONS: This study examines the promoting effect of JAK2 on oxidative stress occurrence in the corpus cavernosum and on the development of DMED in both animal experiments and cell experiments, as well evaluates the inhibitory effect of BB on JAK2 and its therapeutic effect on DMED. The main limitation of our current study is the lack of an appropriate means for activating JAK2. CONCLUSIONS: JAK2 can induce DMED by enhancing oxidative stress and BB can play a role in treating DMED by inhibiting JAK2 and reducing oxidative stress. Our study provides an option and an idea for further studies on the pathogenesis and treatment of DMED. Song J, Tang Z, Li H, et al. Role of JAK2 in the Pathogenesis of Diabetic Erectile Dysfunction and an Intervention With Berberine. J Sex Med 2019;16:1708-1720.
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Berberina/farmacologia , Diabetes Mellitus Experimental/complicações , Disfunção Erétil/fisiopatologia , Janus Quinase 2/metabolismo , Animais , Masculino , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
OBJECTIVE: To investigate the efficiency of microdissection testicular sperm extraction (micro-TESE) in male patients with nonmosaic Klinefelter's syndrome (NMKS), the outcomes of intracytoplasmic sperm injection (ICSI) in their wives, and the possible predictors of clinical pregnancy. METHODS: Forty-nine males with NMKS underwent micro-TESE in our hospital from July 2016 to November 2018. We compared the age, reproductive hormone levels, and testis volume of the patients between the sperm-positive and -negative groups. We performed ICSI for the wives of the sperm-positive patients, recorded the numbers of pregnancies and births, compared the age, reproductive hormone levels and number of mature oocytes between the successful and failed ICSI groups, and analyzed the possible predictors of the results of micro-TESE and outcomes of ICSI. RESULTS: The 49 patients were aged (28.20 ± 3.52) years, all diagnosed as with 47,XXY nonmosaicism by karyotype analysis, with a testis volume of (2.95 ± 0.84) ml, a serum FSH content of (42.42 ± 14.37) IU/L, a serum LH level of (22.50 ± 8.64) IU/L, and a serum T level of (6.64 ± 4.13) nmol/L. Sperm were obtained from 32 of the patients, with a sperm retrieval rate (SRR) of 65.31%, and the wives (aged ï¼»26.79 ± 2.97ï¼½ years) of 29 of the sperm-positive males underwent ICSI, achieving a fertilization rate of (48.14 ± 27.33)%, an available embryo rate of (63.71 ± 28.90)%, a pregnancy rate of 48.28% (14/29), and a birth rate of 24.14% (7/29) up to the present time, with 7 cases awaiting delivery. The 2 cases failing to achieve pregnancy were waiting for transplantation of the frozen embryos. Logistic regression analysis showed that the preoperative serum T level of the NMKS patients had a significant predictive value for the pregnancy rate (AUC = 0.832, cut-off value = 5.17 nmol/L, P = 0.015), but not the other factors for either the SRR or the pregnancy rate. CONCLUSIONS: Sperm can be retrieved from over 60% of the NMKS patients undergoing micro-TESE, and some of them can achieve pregnancy and have their own children by ICSI. Moreover, those with a preoperative serum T level of >5.17 nmol/L are very likely to achieve clinical pregnancy after successful sperm retrieval.
Assuntos
Infertilidade Masculina/terapia , Síndrome de Klinefelter , Microdissecção , Taxa de Gravidez , Recuperação Espermática , Testosterona/sangue , Adulto , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , Espermatozoides , Testículo , Adulto JovemRESUMO
OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP.
Assuntos
Terapia a Laser/métodos , Ereção Peniana , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Humanos , Terapia a Laser/efeitos adversos , Masculino , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Persistent Müllerian duct syndrome (PMDS) is a rare autosomal recessive disorder of sexual development in males, defined by the presence of Müllerian remnants with otherwise normal sexual differentiation. Mutations in anti-Müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes are the main causes of PMDS. In this study, we performed molecular genetic analysis of 11 unrelated cryptorchidism patients using whole-exome sequencing and classified the variants. Three of the 11 patients had biallelic mutations in AMH or AMHR2. Case 1 carried a homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 of AMH (NM_000479 transcript), which is a frameshift mutation, leading to the loss of function of AMH. Case 2 carried compound heterozygous mutations; c.494_502del (p.I165_A168delinsT) in exon 4 and g.6147C>A of AMHR2 (NM_001164690 transcript). Case 3 carried compound heterozygous mutations; c.G1168A (p.E390K) in exon 9 and c.A1315G (p.M439V) in exon 10 of AMHR2 (NM_001164690 transcript). All three patients were admitted due to azoospermia- and oligospermia-caused infertility. They were furtherly diagnosed with PMDS, as pelvic magnetic resonance imaging revealed the presence of Müllerian remnants. Our study suggests that PMDS and genetic analysis should be considered during the differential diagnosis of cryptorchidism.
Assuntos
Hormônio Antimülleriano/genética , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Infertilidade Masculina/fisiopatologia , Mutação , Receptores de Peptídeos/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Adulto , Transtorno 46,XY do Desenvolvimento Sexual/genética , Éxons , Testes Genéticos , Humanos , MasculinoRESUMO
BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.
Assuntos
Berberina/farmacologia , Diabetes Mellitus Experimental/complicações , Disfunção Erétil/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Disfunção Erétil/induzido quimicamente , Lisofosfolipídeos/metabolismo , Masculino , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Ratos , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , EstreptozocinaRESUMO
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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Numerous studies have shown that mammalian target of rapamycin (mTOR) inhibitor activates Akt signaling pathway via a negative feedback loop while inhibiting mTORC1 signaling. In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin-mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors. Moreover, we analyzed the effect of mTORC1 and mTORC2 on regulating cell cycle progression. We found that low concentrations rapamycin increased Akt and ERK phosphorylation through a mTORC1-dependent mechanism because knockdowned raptor induced the activation of Akt and ERK, but higher doses of rapamycin inhibited Akt and ERK phosphorylation mainly via the mTORC2 signaling pathway because that the silencing of rictor led to the inhibition of Akt and ERK phosphorylation. We further showed that mTORC2 was tightly associated with the development of cell cycle through an Akt-dependent mechanism. Therefore, we combined PI3K and ERK inhibitors prevent rapamycin-induced Akt activation and enhanced antitumor effects of rapamycin. Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin-mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin-based therapeutic approaches in cancer cells.
Assuntos
Antibióticos Antineoplásicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos , Neoplasias/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Proteínas , Serina-Treonina Quinases TORRESUMO
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were constructed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.
Assuntos
Antígenos CD/metabolismo , Antígeno B7-1/metabolismo , Evasão Tumoral/genética , Neoplasias da Bexiga Urinária/imunologia , Adulto , Idoso , Antígenos CD/genética , Antígeno B7-1/genética , Antígeno B7-H1 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Bexiga Urinária/metabolismoRESUMO
OBJECTIVE: Castrated rats exhibit significant shrinkage of the ventral prostate and apoptosis of prostatic cells, which can be attributed to the reduced blood supply to the prostate. But what causes the blood decrease in the prostate remains unknown. This study aims to explore the molecular mechanism of the changes in the microcirculation of the ventral prostate of rats following castration. METHODS: We randomized 24 male adult rats into 6 groups of equal number, and collected their ventral prostates at 0, 1/2, 1, 2, 3 and 7 d, respectively, after castration. Then we observed the changes of the microvessels under the transmission electron microscope, detected the apoptosis of endothelial cells by TUNEL, and determined the expressions of VEGF, endostatin, angiostatin and angiopoietin-2 by Western blot. RESULTS: The castrated rats showed dramatic changes in the microvessels of the ventral prostate, obvious apoptosis of the endothelial cells, down-regulated expression of VEGF, and up-regulated expressions of endostatin and angiostatin, while angiopoietin-2 remained unchanged. CONCLUSION: The decreased level of VEGF and increased levels of endostatin and angiostatin might underlie the mechanism of the changes in the microcirculation of the ventral prostate of rats following castration.
Assuntos
Microcirculação , Orquiectomia , Próstata/irrigação sanguínea , Angiopoietina-2/metabolismo , Angiostatinas/metabolismo , Animais , Endostatinas/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the effects of testosterone on the proliferation of penile corpus cavernosal cells in male SD rats. METHODS: Smooth muscle cells (SMCs) and fibroblasts collected from the corpus cavernosal tissues of male SD rats were cultured by the enzymatic dispersion method and detected for the expression of the androgen receptor (AR) by immunohistochemistry. The effects of testosterone on the SMCs and fibroblasts were observed by methyl thiazolyl tetrazolium (MTT) assay in different concentration groups (10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, 10(-4) mol/L and 10(-3) mol/L) in comparison with the control. RESULTS: The AR expression was found in the penile corpus cavernosal tissues. MTT assay showed that, at the concentration of 10(-5) mol/L, testosterone induced the proliferation of SMCs (68100 +/- 2200) and fibroblasts (70200 +/- 1300), with significant differences from the control ( P < 0.05), while at 10(-4) mol/L, it inhibited their proliferation (55000 +/- 1400 and 59100 +/- 1500, respectively), (P < 0.01). No significant effects were noted in the other concentration groups. CONCLUSION: AR exists in the penile corpus cavernosal tissues of male rats. Testosterone modulates the proliferation of corpus cavernosum tissue cells through AR, and different concentrations of testosterone may be positively or negatively correlated with the proliferation of SMCs and fibroblasts.
Assuntos
Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Testosterona/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/metabolismo , Imuno-Histoquímica , Masculino , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Pênis/citologia , Pênis/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismoRESUMO
We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.
Assuntos
Azoospermia/patologia , Azoospermia/terapia , Hormônio Foliculoestimulante/sangue , Recuperação Espermática , Espermatozoides , Testículo/citologia , Testículo/patologia , Adulto , Humanos , Masculino , Microdissecção , Oligospermia/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Síndrome de Células de Sertoli/patologia , Maturação do Esperma , Níveis Máximos PermitidosRESUMO
Solute carrier family 26 member 6 (Slc26a6), which is mainly expressed in the intestines and kidneys, is a multifunctional anion transporter that is crucial in the transport of oxalate anions. This study is aimed at investigating the effect of Slc26a6 expression on oxalate-induced cell oxidation and crystal formation. Lentivirus transfection was used to upregulate or downregulate Slc26a6 expression in NRK cells. Cell viability and apoptosis, reactive oxygen species (ROS) and malondialdehyde (MDA) generation, and superoxide dismutase (SOD) activity were measured. Crystal adhesion and the cell ultrastructure were observed using light and transmission electron microscopy (TEM). Three groups of rats, normal control, lentivirus-vector, and lentivirus-small interfering RNA (lv-siRNA) groups, were used, and after lentivirus transfection, they were fed 1% ethylene glycol (EG) and 0.5% ammonium chloride (NH4Cl) for 2 weeks. Dihydroethidium (DHE), terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labeling (TUNEL), and von Kossa staining were performed, and nuclear factor κB (NFκB) and osteopontin (OPN) expression were measured. In the vitro study, compared to the control group, downregulated Slc26a6 NRK cells showed alleviation of the cell viability decrease, cell apoptosis rate, ROS generation, and SOD activity decrease after oxalate treatment. Crystal adhesion and vesicles were significantly less after oxalate exposure than in the untreated controls. Rats infected with lentivirus-siRNA exhibited attenuated SOD generation, cell apoptosis, and crystal formation in the kidneys. Increased phosphorylation of NFκB and OPN was involved in the pathological process. In conclusion, the results of the present study indicate that reducing the expression of Slc26a6 in the kidney may be a potential strategy for preventing stone formation.
Assuntos
Antiporters/metabolismo , Regulação para Baixo , Espaço Intracelular/metabolismo , Estresse Oxidativo , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Vesículas Citoplasmáticas/metabolismo , Vesículas Citoplasmáticas/ultraestrutura , Rim/patologia , Peroxidação de Lipídeos , Masculino , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Osteopontina/metabolismo , Oxalatos , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transportadores de Sulfato , Fator de Transcrição RelA/metabolismo , Transfecção , TransgenesRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Prostate in combination with an antibiotic for the treatment of chronic nonbacterial prostatitis. METHODS: A double-blind, parallel contrasted, multi-central method was applied in the study. After the Stamey test and expressed prostate secretion (EPS) examination, 160 patients with prostatitis were recruited and randomized into a trial group (80 cases with 1 case missing) and a control group (80 cases). In the trial group, the patients used the levofloxacin and Prostate during the first 4 weeks and Prostate only during the following 4 weeks. In the control group, the patients used the levofloxacin and placebo during the first 4 weeks, and placebo only during the following 4 weeks. Before and 4 and 8 weeks after the treatment, the patients were visited and evaluated by the national institute health-chronic prostatitis symptom index (NIH-CPSI), EPS, and asked about the side. RESULTS: After 4-week and 8-week treatment, the pain index dropped by 3.34 +/- 2.45 and 4.06 +/- 3.03 in the trial group, and effects. 2.28 +/- 2.42 and 3.30 +/- 3.29 in the control; the voiding index dropped by 2.22 +/- 1.79 and 2.77 +/- 2.04 in the trial group, and 1.24 +/- 1.67 and 1.83 +/- 2.25 in the control respectively. There was significant difference between pre-treatment and post-treatment in both the two groups (P < 0.01), while the difference was not significant between 4-week and 8-week post-treatment (P > 0.05). And there was significant difference between the two groups in the pain index and voiding index (P < 0.01), but not in the white blood cell count and lipid in the EPS (P > 0.05). No serious side effects were recorded, and the tolerance to Prostate and placebo showed no significant difference. CONCLUSION: Prostate in combination with an antibiotic can effectively relieve the pain and voiding symptoms and improve the life quality of the patients with nonbacterial prostatitis and well deserves to be recommended in clinical practice.
Assuntos
Antibacterianos/uso terapêutico , Extratos Vegetais/uso terapêutico , Pólen , Prostatite/tratamento farmacológico , Adulto , Doença Crônica , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Masculino , Fitoterapia , Resultado do TratamentoRESUMO
Paragangliomas of the urinary bladder are rare neoplasms derived from chromaffin tissue with a chromosomal imbalance. Their preoperative diagnosis and assessment of malignant potential remain significant challenges for urologists. The current report presents the case of a 34-year-old male who presented with a history of paroxysmal gross hematuria lasting for 7 months. Chromosome duplications were detected by fluorescence in situ hybridization (FISH) in urine exfoliated cells, and the diagnosis was confirmed by histopathology following a transurethral resection. To the best of our knowledge, this is the first reported case of urinary bladder paraganglioma in which chromosomal duplications were detected by FISH in urine exfoliated cells. This may be helpful to its differential diagnosis and malignant potential determination.
RESUMO
OBJECTIVE: To study the microcirculation changes in the ventral prostates of rats after castration and the role of microcirculation during the apoptosis of prostatic cells. METHODS: Thirty-six male adult rats were randomized to 6 groups: one was taken as the control, while the other 5 underwent measurement of the microcirculation in vivo by a D95 physiological signal acquisition system 12 h, 24 h, 72 h, 7 d and 14 d respectively after castration, and then were perfused with Chinese ink to trace the microvessels of the prostates. RESULTS: The microcirculation of the rats'prostates changed dramatically following castration. The diameter and density of the microvessels, especially in the distant and mediate ducts of the prostates, decreased dramatically, and so did the bloodflow velocity. CONCLUSION: The microcirculation plays a role during the process of apoptosis of prostatic cells, and might be the mechanism of " apoptosis shift".
Assuntos
Apoptose/fisiologia , Orquiectomia , Próstata/irrigação sanguínea , Animais , Masculino , Microcirculação , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.