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PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.
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PURPOSE: To explore the association between chronic prostatitis (CP) and the subsequent development of benign prostatic hyperplasia (BPH). METHODS: Data analyzed were medical claims of Taiwan's National Health Insurance program. From 2010 to 2017, 3571 patients â§20 years with CP diagnosed by certified urologists were enrolled. Patients with past BPH diagnosis and diagnosis of prostate cancer, inguinal hernia, interstitial cystitis, and urethritis in the past and within one year after the first CP diagnosis were excluded. Age-matched controls were randomly selected from all non-CP individuals of the same exclusion criteria in the study period with a CP/non-CP ratio of 1:4. The follow-up was made from the first CP diagnosis to death or the end of 2018. The endpoint was the newly diagnosed BPH. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of BPH in association with CP. RESULTS: Over a maximum of 8 years of follow-up, 287 (8.03%) and 258 (0.43%) BPH events were noted for the CP and non-CP group, respectively, representing a covariate adjusted HR (aHR) of 4.30 (95% CI, 3.61-5.13). Younger patients tended to suffer from higher aHRs, especially those aged 20-39 years (aHR: 11.45, 95% CI, 5.12-25.64). CONCLUSION: The Taiwan national health database indicated that CP patients had a significantly higher risk of developing BPH later than non-CP patients. Interestingly, the younger the CP is diagnosed (under 40), the greater the risk.
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Hiperplasia Prostática , Neoplasias da Próstata , Prostatite , Masculino , Humanos , Prostatite/complicações , Prostatite/epidemiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/diagnóstico , Estudos de Coortes , Neoplasias da Próstata/complicações , Doença CrônicaRESUMO
BACKGROUND: Testicular cancer is fairly rare but can affect fertility in adult males. Leucine-rich repeats- and WD repeat domain-containing protein 1 (LRWD1) is a sperm-specific marker that mainly affects sperm motility in reproduction. Our previous study demonstrated the impact of LRWD1 on testicular cancer development; however, the underlying mechanisms remain unclear. METHODS: In this study, various plasmids associated with LRWD1 and miR-320a manipulation were used to explore the roles and regulatory effects of these molecules in NT2D1 cellular processes. A Dual-Glo luciferin-luciferase system was used to investigate LRWD1 transcriptional activity, and qRT-PCR and western blotting were used to determine gene and protein expression. RESULTS: The results suggested that miR-320a positively regulated LRWD1 and positively correlated with NT2D1 cell proliferation but negatively correlated with cell migration and invasion ability. In addition, the miRNA-ribonucleoprotein complex AGO2/FXR1 was shown to be essential in the mechanism by which miR-320a regulates LRWD1 mRNA expression. As miR-320a was required to regulate LRWD1 expression through the AGO2 and FXR1 complex, eEF2 and eLF4E were also found to be involved in miR-320a increasing LRWD1 expression. Furthermore, miR-320a and LRWD1 were responsive to oxidative stress, and NRF2 was affected by the presence of miR-320a in response to ROS stimulation. CONCLUSIONS: This is the first study showing the role of miR-320a in upregulating the testicular cancer-specific regulator LRWD1 and the importance of the AGO2/FXR1 complex in miR-320a-mediated upregulation of LRWD1 during testicular cancer progression.
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Carcinoma , MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Sêmen , Motilidade dos Espermatozoides , Neoplasias Testiculares/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.
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Terapia a Laser , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução Uretral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Próstata/cirurgia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Estudos Retrospectivos , Volatilização , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Sintomas do Trato Urinário Inferior/complicações , Obstrução Uretral/complicações , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Resultado do TratamentoRESUMO
Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.
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Infertilidade Masculina , Qualidade de Vida , Masculino , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Envelhecimento , Estilo de Vida , ObesidadeRESUMO
PURPOSE: The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function. MATERIALS AND METHODS: Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated. RESULTS: Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms. CONCLUSIONS: We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.
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Astenozoospermia , Testículo , Humanos , Masculino , Testículo/metabolismo , Astenozoospermia/genética , Astenozoospermia/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Espermátides/metabolismo , Mitocôndrias/metabolismo , Motilidade dos EspermatozoidesRESUMO
OBJECTIVES: To explore the trends in Fournier's gangrene (FG) incidence and mortality rate in Taiwan and to investigate the contributing factors to such changes. METHODS: Between 2002 and 2016, hospitalized FG patients who underwent subsequent surgical intervention were included in this retrospective study. Incidence, outcomes, age-adjusted Charlson Comorbidity Index (ACCI), hospitalization cost, surgical timing, and the number of multidisciplinary specialists involved in the first-line management of FG in each year were collected. Simple linear regression and Pearson correlation coefficient (r) were used for the subsequent analysis. RESULTS: The national cohort enrolled 2183 FG patients from 2002 to 2016 in Taiwan. The age-standardized incidence rate of FG was between 0.4 and 0.8 per 100 000 population, and overall mortality was 7.8% in these 15 years. We illustrated the downward trendline of FG mortality with a 0.62 coefficient of determination. The mortality of FG patients who underwent surgery within 24 h and after 24 h were found to be 8.3 ± 3.9% and 14.6 ± 25.2%, respectively (p = 0.02). The numbers of urologists, anesthesiologists, emergency doctors, and physicians per 100 000 population had a strong negative linear correlation with FG mortality (r = 0.8, p < 0.001). ACCI score had a moderate linear relationship with FG mortality (r = 0.57, p = 0.027). The hospitalization cost showed a weak linear correlation with FG mortality (r = -0.03, p = 0.92). CONCLUSIONS: We demonstrated the downward trend of the FG mortality rate in Taiwan from 2002 to 2016. Besides underlying comorbidities and surgical timing, sufficient multidisciplinary specialists are essential for the survival benefit of FG patients in Taiwan experience.
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Gangrena de Fournier , Masculino , Humanos , Lactente , Gangrena de Fournier/epidemiologia , Gangrena de Fournier/cirurgia , Estudos Retrospectivos , Taiwan/epidemiologia , Índice de Gravidade de Doença , Modelos LinearesRESUMO
BACKGROUND CONTEXT: Limited studies have investigated risk factors for postoperative urinary retention (POUR) following elective spine surgery. Furthermore, some discrepancies have been found in the results of existing observational studies. PURPOSE: This study aimed to review the available literature on risk factors associated with POUR following elective spine surgery. STUDY DESIGN: A systematic review with meta-analysis was performed. PATIENT SAMPLE: A total of 31,251 patients (POUR=2,858, no POUR=28,393) were included in the meta-analysis. OUTCOME MEASURES: Demographics, type of elective spine surgery, country, definition of POUR, and potential risk factors for POUR were evaluated. METHODS: The Cochrane Library, Embase, and Medline electronic databases were searched to identify relevant studies. Binary outcomes were reported as odds ratio (OR). Weighted mean differences (WMD) or standardized mean differences (SMD), with 95% confidence intervals (CI), were used for meta-analysis of continuous outcomes. RESULTS: Eleven studies (2 prospective and 9 retrospective) were included in the analysis. Patients with POUR were older than those without POUR (WMD, 7.13; 95% CI, 4.50-9.76). Male patients were found to have an increased risk of POUR (OR, 1.31; 95% CI, 1.04-1.64). The following variables were also identified as significant risk factors for POUR: benign prostatic hyperplasia (BPH; OR, 3.79; 95% CI, 1.89-7.62), diabetes mellitus (DM; OR, 1.50; 95% CI, 1.17-1.93), and previous urinary tract infection (UTI; OR, 1.70; 95% CI, 1.28-2.24). Moreover, longer operative time (WMD, 19.88; 95% CI, 5.01-34.75) and increased intraoperative fluid support (SMD, 0.37; 95% CI, 0.23-0.52) were observed in patients with POUR. In contrast, spine surgical procedures involving fewer levels (OR, 0.75; 95% CI, 0.65-0.86), and ambulation on the same day as surgery (OR, 0.65; 95% CI, 0.52-0.81) were associated with a decreased risk of POUR. CONCLUSIONS: Based on our meta-analysis, older age, male gender, BPH, DM, and a history of UTI are risk factors for POUR following elective spine surgery. We also found that longer operative time and increased intravenous fluid support would increase the risk of POUR. Additionally, multi-level spine surgery may have a negative effect on postoperative voiding.
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Retenção Urinária , Idoso , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Coluna Vertebral , Retenção Urinária/epidemiologia , Retenção Urinária/etiologiaRESUMO
OBJECTIVE: To determine whether kidney stone history is associated with adverse outcomes after percutaneous coronary intervention (PCI). Kidney stone formers have an increased risk of developing coronary artery disease; however, whether these patients have worse cardiac outcomes is unknown. MATERIALS AND METHODS: We identified adult patients who underwent first-time PCI in Vanderbilt University Medical Center (VUMC) Synthetic Derivative from 2008 to 2016 (nâ¯=â¯11,289) and in a nationwide database of Taiwan (NHIRD) from 2005 to 2012 (nâ¯=â¯155,762). Odds ratios (ORs) of 30-day in-hospital mortality and hazard ratios (HRs) of 1-year and 3-year adverse outcomes associated with kidney stone history were estimated using a propensity score approach. RESULTS: Overall, 294 and 12,286 stone formers undergoing PCI were identified in the VUMC and NHIRD, respectively. After matching, stone formers at VUMC were at higher risks of 30-day in-hospital mortality (OR 2.79, 95% CI 1.15-6.69) and 1-year (HR 1.59, 95% CI 1.13-2.24) and 3-year (HR 1.36, 95% CI 1.02-1.81) myocardial infarction. In the NHIRD, kidney stone history was associated with 1-year (HR 1.12, 95% CI 1.03-1.21) and 3-year (HR 1.14, 95% CI 1.06-1.22) myocardial infarction. In a sensitivity analysis, stone formers undergoing kidney stone surgery were marginally associated with 30-day in-hospital mortality (OR 1.21, 95% CI 0.99-1.48) and were associated with 3-year myocardial infarction (HR 1.13, 95% CI 1.02-1.25). CONCLUSION: Kidney stone history is associated with poorer cardiac outcomes after PCI. Improving secondary cardiac prevention strategies after PCI may be necessary for patients with a history of kidney stone disease.
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Cálculos Renais/complicações , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
STUDY QUESTION: Does the hypermethylation of the maelstrom spermatogenic transposon silencer (MAEL) promoter and subsequent de-repression of transposable elements represent one of the causes of spermatogenic failure in infertile men? SUMMARY ANSWER: Experimental hypermethylation of a specific region (-131 to +177) of the MAEL promoter leads to decreased expression of MAEL with increased expression of the transposable element LINE-1 (L1) and in infertile men methylation of the MAEL promoter is associated with the severity of spermatogenic failure. WHAT IS KNOWN ALREADY: MAEL induces transposon repression in the male germline and is required for mammalian meiotic progression and post-meiotic spermiogenesis. Patients with non-obstructive azoospermia (NOA), defined as no sperm in the ejaculate due to spermatogenic failure, and histopathologically proven hypospermatogenesis (HS) is not uncommon and its etiology is largely unknown. STUDY DESIGN, SIZE, DURATION: Luciferase reporter assay and a targeted DNA methylation model were used to explore the effects of hypermethylation of MAEL promoter on gene expression. Germ cell-enriched testicular cells from infertile patients were used to determine the methylation levels of MAEL and expressions of MAEL and L1. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six patients with histopathologically proven NOA and HS and 12 patients with obstructive azoospermia and normal spermatogenesis (NS) were enrolled in this study. Demographic and clinical information were obtained. The severity of HS was determined by a spermatogenic scoring system. The methylation levels of 26 CpGs in the MAEL promoter was measured, and quantitative real-time RT-PCR was used to determine the expressional levels of MAEL and L1. MAIN RESULTS AND THE ROLE OF CHANCE: Targeted DNA methylation of MAEL promoter suppressed MAEL expression and de-repressed L1 activity in vitro. Patients with HS had significantly higher mean methylation levels of 26 consecutive CpGs in the MAEL promoter, compared to patients with NS. The MAEL methylation levels were negatively correlated with MAEL transcript levels and higher methylation level of MAEL was associated with severe spermatogenic defect. L1 transcript level was significantly higher in patients with HS. No differences in age, frequency of testicular insults and genetic anomalies was noted between patients with high or low MAEL methylation levels. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Because of the difficulty in the use of human germ cells for study, the in vitro targeted DNA methylation model was performed by using human NCI-H358 cells to explore the effects of MAEL methylation on transposable elements activity. Because the germ cell-enriched testicular cells isolated from a testicular sample were relatively few, the purity of cell populations was not determined. WIDER IMPLICATIONS OF THE FINDINGS: Measurement of the methylation level of MAEL gene may be feasible to predict the severity of spermatogenic failure or the outcome of testicular sperm retrieval. STUDY FUNDING/COMPETING INTERESTS: This work was supported through grants from the Ministry of Science and Technology of Taiwan (100-2314-B-006-017) and National Cheng Kung University Hospital, Tainan, Taiwan (NCKUH 20120266). The authors declare no conflicts of interest.
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Proteínas de Transporte/genética , Metilação de DNA , Infertilidade Masculina/genética , Elementos Nucleotídeos Longos e Dispersos , Espermatogênese/genética , Adulto , Azoospermia/genética , Linhagem Celular Tumoral , Ilhas de CpG , Elementos de DNA Transponíveis , Proteínas de Ligação a DNA , Inativação Gênica , Genes Reporter , Humanos , Infertilidade Masculina/patologia , Masculino , Oligospermia/genética , Fenótipo , Regiões Promotoras Genéticas , Recuperação Espermática , Espermatozoides/metabolismo , Testículo/metabolismo , Fatores de TranscriçãoRESUMO
Primary localized tracheobronchial amyloidosis (TBA) is a rare respiratory tract dysfunction, which is a heterogeneous group of diseases involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in ß-pleated sheets. A 64-year-old man was referred to our hospital because of hemoptysis. Physical examination showed decreased breath sounds in the right lung on auscultation. Chest computed tomography scan displayed multiple nodules with varied size in main bronchia around bilateral hilus of the lung. After admission, bronchoscopy was performed for this patient, and roughness of mucosa in trachea and multiple nodules in respiratory tract were observed. Through further tissue biopsy, the diagnosis of primary TBA was confirmed.
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Amiloidose/diagnóstico , Hemoptise/diagnóstico , Neoplasias da Traqueia/diagnóstico , Biópsia , Neoplasias Brônquicas/diagnóstico , Broncoscopia/métodos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodosRESUMO
Fatal hemoptysis is a serious complication of pulmonary tuberculosis, which can rarely be due to a bronchial aneurysm. Here, we present a case of fatal hemoptysis due to bronchial aneurysm occurred in a 59-year-old patient of Han ethnicity suffering from active pulmonary tuberculosis. Meanwhile, we perform a literature review of reported cases to stress detailed radiological examination is needed prior to bronchoscopy to exclude the possibility of aneurysm existent in proximity to the lesions caused by mycobacterium tuberculosis. Urgent and effective treatment is needed to control such life-threatening bleeding, such as rigid bronchoscopy, endovascular therapy and surgery, and endovascular stent-graft repair.
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Fibroblast growth factor 9 (FGF9) is a multifunctional polypeptide belonging to the FGF family and has functions related to bone formation, lens-fiber differentiation, nerve development, gap-junction formation and sex determination. In a previous study, we demonstrated that FGF9 stimulates the production of testosterone in mouse Leydig cells. In the present study, we used both primary mouse Leydig cells and MA-10 mouse Leydig tumor cells to further investigate the molecular mechanism of FGF9-stimulated steroidogenesis. Results showed that FGF9 significantly activated steroidogenesis in both mouse primary and tumor Leydig cells (p<0.05). Furthermore, FGF9 significantly induced the expression of phospho-Akt at 0.5 and 24 hr, phospho-JNK at 0.25, 0.5, and 24 hr, phospho-p38 at 0.5 hr, and phospho-ERK1/2 from 0.25 to 24 hr in primary Leydig cells (p<0.05). Also, FGF9 significantly up-regulated the expression of phospho-Akt at 3 hr, phospho-JNK at 0.25 hr, and phospho-ERK1/2 at 1 and 3 hr in MA-10 cells (p<0.05). Using specific inhibitors of Akt, JNK, p38, and ERK1/2, we further demonstrated that the inhibitors of Akt and ERK1/2 significantly suppressed the stimulatory effect of FGF9 on steroidogenesis in mouse Leydig cells. In conclusion, FGF9 specifically activated the Akt and ERK1/2 in normal mouse Leydig cells and the Akt, JNK and ERK1/2 in MA-10 mouse Leydig tumor cells to stimulate steroidogenesis.
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Fator 9 de Crescimento de Fibroblastos/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Progesterona/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Immunoblotting , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células Intersticiais do Testículo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas ras/metabolismoRESUMO
External stimuli responsive dual drugs carrier was synthesized with Au nanorods (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5' thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into the duplexes. The cDNA designed with the 5' amine functional group assisted to tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated with the folic acid (FA) to target folate receptors overexpressed in the cancer cells. This targeting vehicle provided remote-controlled delivery of this high toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm diode laser irradiation. The dehybridization set the Dox free to bind the cell nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an active drug. The in vitro and in vivo studies revealed that this external stimulus responsive combination drug delivery was significantly effective.
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Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/instrumentação , Neoplasias/tratamento farmacológico , Oligonucleotídeos/química , Fototerapia , Pró-Fármacos/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Cisplatino/química , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Receptores de Folato com Âncoras de GPI/antagonistas & inibidores , Receptores de Folato com Âncoras de GPI/metabolismo , Humanos , Masculino , Camundongos , Camundongos Nus , Nanotubos/química , Neoplasias/metabolismo , Pró-Fármacos/químicaRESUMO
OBJECTIVE: To evaluate the quality of life in patients who had resection of oral cancer and reconstruction by radial forearm free flaps. METHODS: Quality of life of 49 patients was assessed by means of the 14-item oral health impact profile (OHIP-14) and the medical outcomes study-short form-36 (SF-36) questionnaires 12 months after operation. RESULTS: Forty-one questionnaires were collected (84%). SF-36: the highest-scoring domain were physical role (92.9 ± 2.6) and bodily pain (82.6 ± 5.7), the lowest-scoring domain were vitality (61.5 ± 9.1), followed by role emotion (64.9 ± 6.8) and social functioning (65.2 ± 8.2). OHIP-14: the best-scoring domain were handicap (37.1 ± 15.1) and psychological disability (45.7 ± 11.9), the best-scoring domain were physical pain (64.2 ± 11.7) and functional limitation (61.9 ± 12.9). CONCLUSIONS: Radial forearm free flaps for reconstruction of oral defects after cancer resection could significantly influence the patients' quality of life.
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Neoplasias Bucais/cirurgia , Qualidade de Vida , Adulto , Idoso , Feminino , Antebraço/cirurgia , Retalhos de Tecido Biológico , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele , Inquéritos e QuestionáriosRESUMO
Photothermal cancer therapy using near-infrared (NIR) laser radiation is an emerging treatment. In the NIR region, two biological transparency windows are located in 650-950 nm (first NIR window) and 1000-1350 nm (second NIR window) with optimal tissue transmission obtained from low scattering and energy absorption, thus providing maximum radiation penetration through tissue and minimizing autofluorescence. To date, intensive effort has resulted in the generation of various methods that can be used to shift the absorbance of nanomaterials to the 650-950 nm NIR regions for studying photoinduced therapy. However, NIR light absorbers smaller than 100 nm in the second NIR region have been scant. We report that a Au nanorod (NR) can be designed with a rod-in-shell (rattle-like) structure smaller than 100 nm that is tailored to be responsive to the first and second NIR windows, in which we can perform hyperthermia-based therapy. In vitro performance clearly displays high efficacy in the NIR photothermal destruction of cancer cells, showing large cell-damaged area beyond the laser-irradiated area. This marked phenomenon has made the rod-in-shell structure a promising hyperthermia agent for the in vivo photothermal ablation of solid tumors when activated using a continuous-wave 808 m (first NIR window) or a 1064 nm (second NIR window) diode laser. We tailored the UV-vis-NIR spectrum of the rod-in-shell structure by changing the gap distance between the Au NR core and the AuAg nanoshell, to evaluate the therapeutic effect of using a 1064 nm diode laser. Regarding the first NIR window with the use of an 808 nm diode laser, rod-in-shell particles exhibit a more effective anticancer efficacy in the laser ablation of solid tumors compared to Au NRs.
Assuntos
Ouro/química , Raios Infravermelhos , Nanotubos/química , Radioterapia/métodos , Absorção , Animais , Linhagem Celular Tumoral , Lasers , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos , Nanotubos/toxicidade , Polietilenoglicóis/química , Prata/químicaRESUMO
OBJECTIVE: To compare the clinical characteristics and reproductive outcomes of nonobstructive azoospermic men with uniform early and late maturation arrest. METHODS: Patients with biopsy-documented uniform maturation arrest undergoing testicular sperm retrieval and complete medical records were enrolled in the present study. Their medical history, physical examination findings, testicular volume, serum hormone parameters, genetic anomalies, sperm retrieval, and reproductive outcomes were retrospectively analyzed. RESULTS: In a cohort of 223 nonobstructive azoospermic men, 34 men with uniform maturation arrest (21 early maturation arrest and 13 late maturation arrest) were identified. No significant differences were seen in the age distribution, testicular volume, or hormone parameters between patients with early and late maturation arrest. Only 13 patients (38.2%) had a normal serum follicle-stimulating hormone level and normal testicular volume. Patients with early maturation arrest had a greater frequency of overall genetic anomalies, and patients with late maturation arrest had a greater frequency of previous testicular insults. The sperm retrieval and impregnation rate were nonsignificantly greater in patients with late maturation arrest. CONCLUSION: Maturation arrest has a variety of causes and presents with diverse phenotypes. Not all patients with uniform maturation arrest have a normal follicle-stimulating hormone level or testicular volume. Patients with early maturation arrest have a greater incidence of genetic anomalies and are more likely to have worse reproductive outcomes than are patients with late maturation arrest.
Assuntos
Azoospermia/etiologia , Taxa de Gravidez , Testículo/fisiopatologia , Adulto , Azoospermia/genética , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Gravidez , Estudos Retrospectivos , Maturidade Sexual/genética , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Testículo/crescimento & desenvolvimento , Testículo/patologiaRESUMO
BACKGROUND: Community-acquired pneumonia (CAP) remains one of the leading causes of death from infectious diseases around the world. Most severe CAP patients are admitted to the intensive care unit (ICU), and receive intense treatment. The present study aimed to evaluate the role of the pneumonia severity index (PSI), CURB-65, and sepsis score in the management of hospitalized CAP patients and explore the effect of ICU treatment on prognosis of severe cases. METHODS: A total of 675 CAP patients hospitalized in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively investigated. The ability of different pneumonia severity scores to predict mortality was compared for effectiveness, while the risk factors associated with 30-day mortality rates and hospital length of stay (LOS) were evaluated. The effect of ICU treatment on the outcomes of severe CAP patients was also investigated. RESULTS: All three scoring systems revealed that the mortality associated with the low-risk or intermediate-risk group was significantly lower than with the high-risk group. As the risk level increased, the frequency of ICU admission rose in tandem and LOS in the hospital was prolonged. The areas under the receiver operating characteristic curve in the prediction of mortality were 0.94, 0.91 and 0.89 for the PSI, CURB-65 and sepsis score, respectively. Compared with the corresponding control groups, the mortality was markedly increased in patients with a history of smoking, prior admission to ICU, respiratory failure, or co-morbidity of heart disease. The differences were also identified in LOS between control groups and patients with ICU treatment, heart, or cerebrovascular disease. Logistic regression analysis showed that age over 65 years, a history of smoking, and respiratory failure were closely related to mortality in the overall CAP cohort, whereas age, ICU admission, respiratory failure, and LOS at home between disease attack and hospital admission were identified as independent risk factors for mortality in the high-risk CAP sub-group. The 30-day mortality of patients who underwent ICU treatment on admission was also higher than for non-ICU treatment, but much lower than for those patients who took ICU treatment subsequent to the failure of non-ICU treatment. CONCLUSIONS: Each severity score system, CURB-65, sepsis severity score and especially PSI, was capable of effectively predicting CAP mortality. Delayed ICU admission was related to higher mortality rates in severe CAP patients.