代谢综合征基础与临床系列研究——GRGDSP/7E3对动脉粥样硬化内皮细胞MMPs的mRNA表达的影响

目的了解GRGDSP/7E3对基质金属蛋白酶（MMP-2,MMP-9）mRNA表达的影响。方法体外培养人脐静脉内皮细胞,分别用酶谱法和逆转录聚合酶链式反应（RT-PCR）检测MMP-2,MMP-9活性和mRNA表达。待细胞融合成单层后,分别加入无血清培养基、静息期血小板、活化后血小板及interleukin-1β（IL-1β）,共同培养60min后,洗去血小板,内皮细胞继续培养6h。上清液及细胞分别用于酶谱法检测MMP-2和MMP-9活性,以及RT-PCR分析mRNA表达。结果内皮细胞与活化血小板共同培养后,酶谱法显示：与对照组相比,未活化的血小板轻微诱导MMP-2和MMP-9分泌,而活化状态的血小板能显著诱导这二者的分泌,与IL-1β的作用相当;而且还可以见到62kDaMMP-2活化形式。加入阻断剂GRGDSP以及GPⅡb/Ⅲa单克隆抗体（7E3）作用后检测发现,MMP-2和MMP-9分泌减少。与活化血小板共同培养后的内皮细胞表面表达uPAR和MT1-MMP以及上清液中MMP-2的mRNA与对照组相比明显增高,而静息状态的血小板作用不显著。加入GRGDSP或7E3后,mR-NA的表达降低。结论①活化状态的血小板与IL-1β的作用相当,能显著诱导MMP-2和MMP-9分泌;能明显增高内皮细胞（EC）-uPAR和MT1-MMP及上清液中MMP-2mRNA的表达;②GPⅡb/Ⅲa阻断剂可能抑制血小板在不稳定斑块部位聚集、粘附等一系列炎症反应。     

Effect of cigarette smoking on sexual functions,psychological factors,and disease activity in male patients with ankylosing spondylitis

Objective: This study aims to investigate the effect of smoking on sexual functions in AS patients.

Patients and methods: A total of 67 male AS patients with a median age of 34 years (range: 18–57) reporting sexual activity at least for the past 4 weeks period were included. Patients were divided into smokers (Group 1, n?=?47) and non-smokers (Group 2, n?=?20). Fagerström test for nicotine dependence, smoking history, exhaled carbon monoxide test were recorded for smoking AS patients. Visual analogue scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL), International Index of Erectile Function (IIEF), Beck Depression Inventory (BDI) were filled for both groups.

Results: There was no significant difference between smokers and non-smokers in all evaluation parameters. BASMI scores were significantly lower in the mild dependency subgroup as compared to those with moderate or severe dependency (p?=?.005 and p?=?.007, respectively). Total IIEF score and IIEF categories correlated significantly with BASDAI, BASFI, BASMI, ASQoL, pain, fatigue, and cumulative smoking. BDI showed an inverse correlation with the IIEF score and IIEF category (p?r?=?–0.520, p?r?=?–0.508, respectively).

Conclusions: Sexual function in AS patients is associated with the pain, fatigue, disease activity, functional status, quality of life, depression as well as the cumulative exposure to smoking, and that sexual functions tend to decline with increasing degree of cigarette dependency.     

Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia

Introduction: Tadalafil is a promising phosphodiesterase (PDE) 5 inhibitor prescribed for erectile dysfunction (ED). Daily low dose (5?mg) of tadalafil has also been used for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). PDE5 inhibitors induce relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels. The aim of this study was to investigate the efficacy of tadalafil on vessels endothelial function, in patients with male LUTS symptoms associated with BPH.

Methods: The Institutional Review Board (IRB) approved this clinical study and informed consents had been obtained from 81 BPH patients.

The following male LUTS parameters: international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), voiding volume, max and mean voiding flow on voiding flowmetry examination and post-voiding residual urine (RU) were compared at 0, 1, 3, 6, and 12 months after a daily dose of 5?mg tadalafil.

In addition, erectile function was evaluated by the sexual health inventory for men (SHIM) score and vessels endothelial function and peripheral neuropathy were assessed by the brachial-ankle pulse wave velocity (baPWV), ankle brachial index (ABI), and vibration perception threshold (VPT) at 0, 3, 6, and 12 months after treatment.

Results: The mean age of 81 patients was 66.4?±?11.4 years old. Their prostate size was 30.2?±?22.1?ml.

Male LUTS parameters including IPSS, OABSS, and RU showed significant improvement from 1 to 12 months after tadalafil administration. Max and mean voiding flow was significantly increased at 6 months after tadalafil treatment.

The SHIM score showed significant improvement after 3 months. Whilst, the results of baPWV also showed significant improvement from 3 to 12 months. ABI was also significantly improved at 6 months. However, there was no change in the VPT at any time point.

Conclusions: Tadalafil is effective for both male LUTS and ED. It is also shown that tadalafil improves baPWV, which we can conclude that higher vessels elasticity has been obtained. This major finding of this study shows that tadalafil has the potency to improve vessels endothelial dysfunction in patients with BPH.     

The reproductive health indices and sex hormone levels in middle-aged and elderly Chinese men

Objective: The aim of this study was to analyze the age-related recession trajectory of reproductive health indices in middle-aged and elderly Chinese men.

Methods: A population-based cross-sectional study was conducted in Jiashan County, Zhejiang in 2012. Healthy men between 40 and 80 years of age were considered eligible for the study. Physical examination and the sex hormones were measured. The subjects were assessed based on the 5-item version of the International Index of Erectile Function (IIEF-5) for Erectile Dysfunction (ED), and Aging Males’ Symptoms (AMS) scale for Symptomatic Late-Onset Hypogonadism (SLOH).

Results: TG showed a decrease at age 60 years. Testis volume and TT did not show significant difference among the four age groups; cFT began to decrease at age 50 years and Bio-T decreased faster at age 50 years. SHBG and LH increased faster at age 50 and 70 years, respectively. IIEF5 score decrease faster at age 60 years. AMS scores increased faster at age 70 years. With the increase in age, the symptoms of ED and SLOH became severer.

Conclusion: Different indices on reproductive health of men showed turning points at different ages. At first, androgenic sex hormones decreased faster, and then erectile dysfunction got severer, and the last overall male syndromes declined.     

Association between long-term erectile dysfunction and biochemical recurrence after permanent seed I125 implant brachytherapy for prostate cancer. A longitudinal study of a single-institution

We aimed to investigate the predictive factor of erectile dysfunction (ED) in prostate cancer (PCa) patients who underwent low-dose permanent I¹²⁵ seed implant brachytherapy and to investigate if ED could represent a patient’s reported outcome measures (PROMs) of efficacy of BT and indirectly associated with biochemical recurrence free survival (BRFS). From 2000 to 2012, 176 consecutive patients with low-risk PCa underwent BT. ED was evaluated with the International Index of Erectile Function (IIEF-5). Cox regression analysis was performed to assess significant predictors of mild-to-severe ED and BRFS after BT, including covariates. The 10-year actuarial rate of ED was 66%. Subjects with severe ED had higher values of D90 (183.0 versus 177.0; p?p?p?p?=?0.20), while D90?≤?180?Gy independently predicted BCR (HR: 4.65; [95%CI: 1.25–17.34]; p?125 implant, but it is not associated with better BRFS.     

Are urge incontinence and aging risk factors of erectile dysfunction in patients with male lower urinary tract symptoms?

Introduction: Several studies have indicated that erectile dysfunction (ED) patients also suffer from lower urinary tract symptoms (LUTS). We investigated a group of men with LUTS and assessed their sexual function with the aim of being able to predict ED risk factors and introduce ED treatments earlier for this patient group.

Methods: International Prostate Symptom Score (IPSS), Overactive Bladder Symptoms Score (OABSS) and Sexual Health Inventory for Men (SHIM) score were obtained from 236 men with LUTS at their first out-patients visit. Clinical parameters such as body mass index, prostate volume, residual urine volume and prostate specific antigen were also evaluated. The relationship between the SHIM score and other clinical data was analyzed.

Results: According to the SHIM score, ED in men with LUTS was severe 15%, moderate 19%, moderate to mild 28%, mild 17%, normal 7% and data was incomplete in 14%. Based on the results of a multivariate analysis, aging (p?p?=?0.024) were significantly correlated to severe and moderate ED. Furthermore, among OAB symptoms score items, urge urinary incontinence was a risk factor for severe and moderate ED (p?=?0.005).

Conclusion: Aging and OAB (notably urinary urge incontinence) are risk factors for severe and moderate ED in men with LUTS.     

The impact of age,BMI and sex hormone on aging males’ symptoms and the international index of erectile function scores

Objective: To analyze the impact of age, BMI and sex hormone on aging males’ symptoms (AMS) and the 5-item version of the international index of erectile function (IIEF-5) scores in middle-aged and elderly Chinese men.

Methods: A population-based cross-sectional study was conducted in Jiashan County. A total of 969 men, aged between 40 and 80 years old, were admitted. Physical examination and the sex hormones were measured, and AMS and IIEF-5 scores were assessed.

Results: The oneway ANOVA analysis indicated older age groups had higher AMS total-scores, somatic and sexual sub-scores, and lower IIEF5 scores (all p?r_pairwise) analyses showed the significant associations between AMS and age or sex hormone (cFT, Bio-T, SHBG, and LH) levels, and similar for IIEF5. However, when age was adjusted, the correlation coefficients (r_partial) weakened, and correlation significance disappeared, except LH (for AMS: r_partial?=?0.096, p?=?.009; for IIEF-5: r_partial?= ?0.140, p?=?.001). Multiple linear regressions confirmed the influence of increased age and LH on the AMS and IIEF5 scores.

Conclusion: CFT, Bio-T and SHBG failed to yield any additional predicting information when age was adjusted. To improve the male reproductive health, future research should pay more attention on aging-related comorbidities and how to improve general wellness.     

Association of the modified frailty index with adverse outcomes after penile prosthesis implantation

Objectives: To investigate frailty as a predictor of surgical outcome in elderly patients undergoing penile prosthesis implantation.

Material and methods: A total of 54 elderly patients, above 60 years of age, underwent penile prosthesis implantation between 2012 and 2014. Their data were collected and retrospectively analyzed. A modified frailty index (mFI) was calculated for each patient based on 11 risk factors from the Canadian Study of Health and Aging Frailty Index. The 1-year adverse outcomes were correlated with mFI, patients’ and procedure’s risk factors.

Results: Mean age was 64.9?±?5.2 years. No mortality was reported in our patients, however, one-year adverse outcomes were encountered in 43 (79.6%) patients. Among all studied variables, the 1-year adverse outcomes was not significantly association with mFI, but with preoperative glycosylated hemoglobin A1c (HbA1c) (p?=?0.031) and associated Peyronie’s disease (PD) (p?=?0.000). HbA1c, dyslipidemia, hypertension, PD and duration of the procedure were predictive of infection complications (p?Conclusions: mFI is not a predictive of post-penile prosthesis implantation adverse outcomes in elderly patients with impotence. Degree of diabetic control and association with PD was associated with the 1-year adverse outcomes and infection complications.     

Aging and sexual health: getting to the problem

Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data. It also highlights areas that are in need of more research. The search strategies yielded total records screened from PubMed. Clarification of the molecular mechanisms that accompanies corpus cavernosum aging and aging-associated ED will aid new perspectives in the development of novel mechanism-based therapeutic approaches. Age is not a limiting factor for ED medical management, and it is never too late to treat. Hypogonadism should be managed regardless of age, and synergistic effects have been found during testosterone (T) replacement therapy when used along with oral phosphodiesterase-5 (PDE-5) inhibitors. Therefore, the clinical management of ED related to aging can be done by therapeutic interventions that include PDE-5 inhibitors, and other pharmacological treatments.     

Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome

Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low HDL cholesterol and hypertension), which identifies subjects at high risk for forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently, a close association between MetS, erectile dysfunction (ED) and male hypogonadism has been reported. In patients with MetS, hypogonadism can exacerbate sexual dysfunction and arteriogenic ED because of its typical symptoms, such as decreased sexual desire and mood disturbances. On the other hand, hypogonadism per se has been associated with an increased risk of CV and overall mortality. Obesity and in particular central obesity is nowadays considered the most important determinant of MetS-induced hypogonadism whereas hypertension and diabetes play a major role in ED associated with MetS. This review analyses the current literature regarding the relationship between ED, MetS and hypogonadism emphasising the epidemiological and psychopathological aspects and stressing the concept that ED subjects are ‘lucky’, because ED offers a unique chance to undergo medical examination and therefore to improve not only their sexual but, most importantly, their overall health.