Relationship Between Depression and Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

This article provides an overview of current data on the relationship between depression and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), with a focus on pathophysiology and patient management implications. Review of the literature indicated a clear relationship between LUTS secondary to BPH and depression. It is unknown whether this relationship is bidirectional or unidirectional. Depression is associated with the impact of LUTS on quality of life in men with BPH. Research suggests that depression alters the experience of LUTS in this population. Medical and surgical treatments for BPH may impact quality of life and, therefore, depression. Results conflict on the exact nature of the relationship examined, and on the extent to which the relationship may be attributed to physiological factors such as inflammation. Practicing clinicians should consider using a brief self-administered scale to assess for depression in patients with BPH. There is a clear need for additional research to decisively determine the nature of the relationship between LUTS secondary to BPH and depression, as well as the extent to which change in either condition may be affected by the other.Key words: Benign prostatic hyperplasia, Depression, Lower urinary tract symptomsThe prevalence of benign prostatic hyperplasia (BPH) increases with age.¹ Approximately half of men over age 40 are diagnosed with BPH. Of these men, approximately 50% will develop significant and bothersome lower urinary tract symptoms (LUTS) secondary to BPH, which increase in prevalence between ages 40 and 80 years. LUTS secondary to BPH is associated with decreased quality of life and may include urgency/frequency, incontinence, and nocturia. Symptom severity is impacted by the degree of prostatic enlargement, which is highly variable.¹Depression is another common condition that severely and negatively impacts quality of life, with an estimated lifetime prevalence of 16.5% according to the National Institute of Mental Health.² Depression plays a role in the pathogenesis of a number of chronic diseases, including inflammatory bowel disease, arthritis, asthma, and diabetes³; a relationship has also been identified between depression and urologic diagnoses such as incontinence.⁴ Symptoms of BPH are associated with decreased quality of life and depression, and the literature strongly suggests that there may also be a pathophysiologic relationship between BPH and depression^5,6; in addition, depressive symptoms are also associated with treatments for BPH.^7–9Research has suggested that psychiatric parameters such as depression may have a putative role in the development of LUTS secondary to BPH.⁶ Furthermore, depression may pose an impediment to effective treatment for these patients. Improved understanding of the relationship between BPH and depression could lead to improved management. This area of research is important because clinical depression is associated with a significant increase in mortality, and early detection, intervention, and treatment of clinically relevant depressive symptoms are key factors in patient care.¹⁰Fewer studies have focused on the relationship between depressive symptoms or depressive disorders and BPH, or the nature and direction of this relationship. Thus, a systematic review of the relationship between depression and BPH is needed. We provide a comprehensive summary of contemporary published reports on LUTS secondary to BPH and depression to improve understanding of the relationship between these two conditions and provide a framework for future investigation.     

Predictors of Individual Response to Placebo or Tadalafil 5mg among Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: An Integrated Clinical Data Mining Analysis

Background

A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown.

Methods

This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface.

Findings

International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group

Conclusions

This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the treatment of LUTS-BPH in the majority of patients and the importance of evaluating individual patient need in selecting the most appropriate treatment.     

Comparative Effectiveness of Oral Drug Therapies for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis

Introduction

Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.

Materials and Methods

An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs) comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.

Results

A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs) plus phosphodiesterase 5 inhibitors (PDE5-Is) ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax) with a mean difference (MD) of 1.98 (95% CI, 1.12 to 2.86) as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs) ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.

Conclusions

Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other pharmacologic agents alleviate the symptoms of LUTS/BPH.     

Medical Attendance for Lower Urinary Tract Symptoms Is Associated with Subsequent Increased Risk of Outpatient Visits and Hospitalizations Based on a Nationwide Population-Based Database

Introduction

Lower urinary tract symptoms (LUTS), which encompass storage, voiding, and postmicturition symptoms, are highly prevalent and recognized globally. Based on a nationwide population-based database, this study tests the hypothesis that medical attendance for LUTS is associated with a subsequent increase in the number of outpatient visits and hospitalizations, with differences among medical specialties and age groups.

Methods

Participants were selected from a random population sample of approximately one million people as a representative cohort of National Health Insurance (NHI) enrollees in Taiwan. Participants had at least three outpatient service claims with a coding of LUTS during the recruitment period 2001–2004. Both the LUTS group and non-LUTS control group were monitored for subsequent outpatient visits and hospitalizations, excluding LUTS-related healthcare services, for 2 years following the index date. The results were categorized based on medical specialty and age group.

Results

The outpatient visit rates (no. per person-year) and adjusted incidence rate ratios (IRRs) (95% confidence interval (CI) were significantly higher in urology (4.51, 95%CI 4.15–4.91) and gynecology (1.82, 95%CI 1.76–1.89) for the LUTS group. They were also significantly high in other departments, including internal medicine (1.25), general practice (1.13), Chinese medicine (1.77), family medicine (1.19), surgery (1.38), and psychiatry (1.98). Similarly, the hospitalization rate (no. per 1000 person-year) and adjusted IRRs (95% CI) were significantly higher in urology (5.50, 95% CI = 4.60–6.50) and gynecology (1.60, 95% CI = 1.35–1.90), as well as in internal medicine (1.55) and surgery (1.56), but not in psychiatry (1.12). Furthermore, the IRRs differed among 3 age groups.

Conclusions

A significantly higher number of outpatient visits and hospitalizations were observed for individuals with LUTS, compared to the control group, and the effects differed with the advancement of age. This study broadens understanding of LUTS by viewing their impact on healthcare services with multiple and overlapping systems, rather than considering them exclusively as symptoms of traditional diseases of the bladder and urethra.     

Cardiovascular Risk Factors and Ethnicity Are Independent Factors Associated with Lower Urinary Tract Symptoms

Objectives

To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.

Materials and Methods

We conducted a cross-sectional study of 1021 men aged 40–79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses.

Results

There were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity.

Conclusion

Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.     

Diabetes Mellitus in Patients with Benign Prostatic Hyperplasia

Of 51 patients submitted to operation for benign prostatic hyperplasia three (5.9%) were knwon, diabetics and two others had undergone surgery for peptic ulcer. Of the remaining patients half (23 out of 46) were found to be diabetic; 40% (20 patients) had a history of previous cardiac infarction or electrocardiograph evidence of myocardial ischaemia.It is suggested that these findings add further support to the hypothesis that benign prostatic hyperplasia is one manifestation of a relative increase of oestrogen secretion with advancing age.     

Custom 4-Plex DiLeu Isobaric Labels Enable Relative Quantification of Urinary Proteins in Men with Lower Urinary Tract Symptoms (LUTS)

The relative quantification of proteins using liquid chromatography mass spectrometry (LC-MS) has allowed researchers to compile lists of potential disease markers. These complex quantitative workflows often include isobaric labeling of enzymatically-produced peptides to analyze their relative abundances across multiple samples in a single LC-MS run. Recent efforts by our lab have provided scientists with cost-effective alternatives to expensive commercial labels. Although the quantitative performance of these dimethyl leucine (DiLeu) labels has been reported using known ratios of complex protein and peptide standards, their potential in large-scale proteomics studies using a clinically relevant system has never been investigated. Our work rectifies this oversight by implementing 4-plex DiLeu to quantify proteins in the urine of aging human males who suffer from lower urinary tract symptoms (LUTS). Protein abundances in 25 LUTS and 15 control patients were compared, revealing that of the 836 proteins quantified, 50 were found to be differentially expressed (>20% change) and statistically significant (p-value <0.05). Gene ontology (GO) analysis of the differentiated proteins showed that many were involved in inflammatory responses and implicated in fibrosis. While confirmation of individual protein abundance changes would be required to verify protein expression, this study represents the first report using the custom isobaric label, 4-plex DiLeu, to quantify protein abundances in a clinically relevant system.     

Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension

Objective

Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders.

Methods

A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable.

Results

Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916–0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension.

Conclusion

Serum bilirubin is inversely associated with increased arterial stiffness in men with pre-hypertension but not normotension. The association between bilirubin level and arterial stiffness was not found significant in women.     

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

The histology‐based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label‐free LC‐MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate‐derived proteins including IGKV3D‐20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D‐20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.     

Lower Urinary Tract Symptoms,Depression, Anxiety and Systemic Inflammatory Factors in Men: A Population-Based Cohort Study

Background

The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression. This study aimed to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders.

Methods

Participants were randomly-selected from urban, community-dwelling males aged 35–80 years at recruitment (n = 1195; sample response rate:67.8%). Of these, 730 men who attended baseline (2002–5) and follow-up clinic visits (2007–10), with complete outcome measures, and without prostate or bladder cancer and/or surgery, neurodegenerative conditions, or antipsychotic medications use, were selected for the present study. Unadjusted and multi-adjusted regression models of incident storage and voiding LUTS and incident depression and anxiety were combined with serum inflammatory markers (high-sensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin–6 (IL–6), myeloperoxidase (MPO), soluble e-selectin (e-Sel)) and socio-demographic, lifestyle, and health-related factors. Hierarchical multiple regression was used to assessed the moderating effect of inflammatory markers.

Results

The incidence of storage, voiding LUTS, depression and anxiety was 16.3% (n = 108), 12.1% (n = 88), 14.5% (n = 108), and 12.2% (n = 107). Regression models demonstrated that men with depression and anxiety at baseline were more likely to have incident storage, but not voiding LUTS (OR: 1.26, 99%CI: 1.01–4.02; and OR:1.74; 99%CI:1.05–2.21, respectively). Men with anxiety and storage LUTS at baseline were more likely to have incident depression (OR: 2.77, 99%CI: 1.65–7.89; and OR:1.45; 99%CI:1.05–2.36, respectively), while men with depression and voiding LUTS were more likely to have anxiety at follow-up (OR: 5.06, 99%CI: 2.81–9.11; and OR:2.40; 99%CI:1.16–4.98, respectively). CRP, TNF-α, and e-Sel were found to have significant moderating effects on the development of storage LUTS (1.06, 0.91–1.96, R² change: 12.7%), depression (1.17, 1.01–1.54, R² change: 9.8%), and anxiety (1.35, 1.03–1.76, R² change: 10.6%), respectively.

Conclusions

There is a bidirectional relationship between storage, but not voiding, LUTS and both depression and anxiety. We observed variable moderation effects for selected inflammatory markers on the development of depression, anxiety and storage LUTS.     

老年良性前列腺增生夜尿病因特点及相关因素分析

目的:探索老年良性前列腺增生夜尿病因特点及相关因素。方法:选取49~84岁年龄段并已明确诊断为前列腺增生(BPH)的男性患者及没有进行过治疗或服用药物者120例。所有患者按照IPSS评分中夜尿频率从0~5分为6组,记录和测量研究对象的各项指标,包括国际前列腺症状评分(IPSS)、生活质量(QOL)、剩余尿量(PVR)、最大尿流率(Qmax)、前列腺体积(TPV)和排尿量(V)。结果:夜尿频率为0~1次者共38例(31.7%),平均QOL评分为2.43;夜尿频率为2~3次者共50例(41.7%),平均QOL评分为3.87;夜尿频率为4次以上者共32例(26.7%),平均QOL评分为5.23。不同组的夜尿频率BPH患者间的QOL评分具有显著性差异(P0.05);多因素Logistic回归分析表明,BPH患者的年龄和PVR是夜尿频率增高的危险因素(P0.05),而TPV和Qmax与夜尿频率的关系无统计学意义(P0.05)。结论:夜尿频率的增多明显影响老年人的生活质量,并且随着老年人的年龄、残余尿量的增加,夜尿频率出现增加的趋势;但前列腺的体积和最大尿流率与夜尿频率无关。     

(Arylpiperazinyl)cyclohexylsufonamides: discovery of alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS)

Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1) blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited.     

Calcium Antagonists Use and Its Association with Lower Urinary Tract Symptoms: A Cross-Sectional Study

Background

Lower urinary tract symptoms (LUTS) have been reported amongst the side effects of calcium antagonists (CA). CAs act on the bladder by affecting the ability of the detrusor muscle to create enough contractile force to overcome obstruction to normal voiding. We aimed to determine the relationship between CA use and LUTS in general medical inpatients.

Methods and Findings

In this cross-sectional study we recruited 278 medical inpatients (including 85 CA users) aged ≥40 (72.1±13.7) years. LUTS was assessed using the International Prostate Symptoms Score (IPSS) questionnaire. A Logistic regression model using a ‘backwards-elimination’ strategy was used to identify variables associated with LUTS and for calculating the adjusted odds ratios and the 95% confidence intervals (CI). After adjusting for other risk factors and drugs, patients on amlodipine/nifedipine and diltiazem/verapamil (compared to non-users) were more likely to suffer from severe LUTS [Males: 12.45(CI: 1.57–98.63) and Females: 7.75(CI: 0.94–63.94)] and moderate-to-severe LUTS [Males: 17.43(CI: 2·26–134.39) and Females: 47.8(CI: 6.22–367.37)]. Patients on felodipine/lercanidipine were less likely to suffer from either severe or moderate-to-severe LUTS. Further, 19 (22.4%) CA-users were on treatment for LUTS compared to 18 (9.3%) of the non-users group, p = 0.003. Both male and female CA-users were three times more likely to be on alpha-blockers than non-users, p<0.001. CA-users were more likely to have undergone urinary tract-related surgery (Males: two times, p = 0.07 and females: nine times, p = 0.029). The study was limited by the fact that a causal relationship could not be established between CA use and LUTS.

Conclusions

Our results demonstrate an association between CA use and an increasing severity of LUTS. They also demonstrate that CA-users are more likely to have medical or surgical treatment for LUTS. However, these CA’s effects on LUTS vary, and the use of highly vascular selective agents does not appear to pose significant risk.     

Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease

Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson’s correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p < 0.001), NO (p < 0.001), and CRP levels were significantly higher in CLD patients than in control subjects. The antioxidant vitamin C (p < 0.001) and trace element zinc (p < 0.001) were comparatively lower in the CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.     

Intravesical Resiniferatoxin for the Treatment of Storage Lower Urinary Tract Symptoms in Patients with Either Interstitial Cystitis or Detrusor Overactivity: A Meta-Analysis

Background

While Resin­iferatoxin (RTX) has been widely used for patients with storage lower urinary tract symptoms (LUTS), its clinical efficiency hasn''t yet been well evaluated. A meta-analysis was performed to evaluate the exact roles of intravesical RTX for the treatment of storage LUTS in patients with either interstitial cystitis (IC) or detrusor overactivity (DO).

Methods

A meta-analysis of RTX treatment was performed through a comprehensive search of the literature. In total, 2,332 records were initially recruited, 1,907 from Elsevier, 207 from Medline and 218 from the Web of Science. No records were retrieved from the Embase or Cochrane Library. Seven trials with 355 patients were included and one trial was excluded because of the lack of extractable data. The analyses were all performed using RevMan 5.1 and MIX 2.0.

Results

Bladder pain was significantly reduced after RTX therapy in patients with either IC or DO. The average decrease of the visual an alogue pain scale was 0.42 after RTX treatment (p = 0.02). The maximum cystometric capacity (MCC) was significantly increased in patients with DO (MCC increase, 53.36 ml, p = 0.006) but not in those with IC (MCC increase, −19.1 ml, p = 0.35). No significant improvement in urinary frequency, nocturia, incontinence or the first involuntary detrusor contraction (FDC) was noted after RTX therapy (p = 0.06, p = 0.52, p = 0.19 and p = 0.41, respectively).

Conclusions

RTX could significantly reduce bladder pain in patients with either IC or DO, and increase MCC in patients with DO; however, no significant improvement was observed in frequency, nocturia, incontinence or FDC. Given the limitations in the small patient size and risk of bias in the included trials, great caution should be taken when intravesical RTX is used before a large, multicenter, well-designed random control trial with a long-term follow-up is carried out to further assess the clinical efficacy of RTX in in patients with storage LUTS.     

血清降钙素原、C反应蛋白/白蛋白比值联合尿白细胞酯酶对复杂性肾结石患者经皮肾镜碎石术后发生尿路感染的预测价值分析

摘要 目的：探讨血清降钙素原（PCT）、C反应蛋白（CRP）/白蛋白（ALB）比值联合尿白细胞酯酶（LEU）对复杂性肾结石患者经皮肾镜碎石术（PCNL）后发生尿路感染的预测价值。方法：选择2015年3月-2021年6月我院收治的128例行PCNL的复杂性肾结石患者作为观察对象,术后定期随访,统计尿路感染情况,根据是否发生术后尿路感染分为尿路感染组和非尿路感染组。比较两组PCT水平、LEU,CRP/ALB比值及其他临床资料。采用多因素Logistic回归分析术后尿路感染的危险因素,绘制受试者工作特征（ROC）曲线,分析PCT、CRP/ALB比值、LEU单独以及联合检测预测术后尿路感染的价值。结果：尿路感染组的血清PCT、CRP/ALB高于非尿路感染组（P<0.05）。尿路感染组的LEU呈阳性,而非尿路感染组的LEU呈阴性。两组在既往泌尿道手术史、手术时间、导尿管留置时间、住院时间、术前尿路感染、结石负荷、使用>3种抗菌药物、合并肾功能障碍、术中通道类型、术前血糖水平方面对比有统计学差异（P<0.05）。既往泌尿道手术史、手术时间≧100 min、导尿管留置时间≧7 d、术前尿路感染、结石负荷≧1000 mm2、术前血糖水平高、合并肾功能障碍是复杂性肾结石患者PCNL后发生尿路感染的危险因素（P<0.05）。PCT、CRP/ALB、LEU单独预测PCNL后尿路感染的曲线下面积（AUC）分别为0.712（0.476～0.944）、0.686（0.436～0.931）、0.836（0.753～0.918）,三者联合预测PCNL后尿路感染的AUC为0.879（0.785～0.972）,均高于PCT、CRP/ALB、LEU单独预测。结论：复杂性肾结石患者PCNL后发生尿路感染的影响因素较多,包括导尿管留置时间、住院时间、结石负荷等,且PCNL后发生尿路感染患者PCT、CRP/ALB比值偏高,LEU呈阳性,三者可能作为PCNL后发生尿路感染的生物标记物。     

地奥司明对前列腺增生伴前列腺炎患者HSP, CRP及PSA的影响

目的:探讨地奥斯明对前列腺增生伴前列腺炎患者血清热休克蛋白(HSP)、C反应蛋白(CRP)及血清PSA水平的影响。方法:选取已确诊为前列腺增生伴前列腺炎的患者39例,随机分为实验组及对照组。对照组19例,予普适泰片治疗;实验组20例,予地奥司明治疗。28天为一个治疗疗程。比较两组患者治疗前后热休克蛋白、C反应蛋白及血清PSA水平的变化。结果:实验组总有效率(95.0%)高于对照组(78.9%),差异具有统计学意义(P0.05);与对照组比较,实验组热休克蛋白、C反应蛋白及血清PSA水平较低(P0.05),慢性前列腺炎评分(NIH-CPSI)评分较低(P0.05),不良反应发生率(10.0%)低于对照组(31.6%),差异存在统计学意义(P0.05)。结论:地奥司明片可以明显改善男性前列腺增生伴前列腺炎患者的排尿困难及尿频尿急等症状,有效降低患者热休克蛋白、C反应蛋白及血清PSA水平。     

百乐眠胶囊联合alpha-受体阻滞剂 治疗良性前列腺增生症引起的夜尿症

目的:观察百乐眠胶囊联合α-受体阻滞剂治疗良性前列腺增生症引起的夜尿症的疗效。方法:随机选取符合良性前列腺增生症诊断,采用α-受体阻滞剂单药治疗,夜尿仍大于等于2次的患者20例,在继续服用α-受体阻滞剂治疗的基础上,加用百乐眠胶囊,每日2次,每次4粒。加用百乐眠胶囊前和用药1个月后,分别采用国际前列腺症状评分表(International Prostate Symptom Score,IPSS),生活质量指数(quality of life index,QoL),膀胱过度活动症评分表(Overactive Bladder Symptom Score,OABSS)进行评估。结果:加用百乐眠胶囊1月后,IPSS评分表中夜尿评分从2.88降至2.41(P=0.03),OABSS评分表总分从6.31降至5.38(P=0.03),夜尿评分从2.63降至2.13(P=0.01),QoL评分无显著变化。结论:百乐眠胶囊联合α-受体阻滞剂治疗良性前列腺增生症引起的夜尿症有较好的疗效。     

Increased Expression and Protein Divergence in Duplicate Genes Is Associated with Morphological Diversification

The differentiation of both gene expression and protein function is thought to be important as a mechanism of the functionalization of duplicate genes. However, it has not been addressed whether expression or protein divergence of duplicate genes is greater in those genes that have undergone functionalization compared with those that have not. We examined a total of 492 paralogous gene pairs associated with morphological diversification in a plant model organism (Arabidopsis thaliana). Classifying these paralogous gene pairs into high, low, and no morphological diversification groups, based on knock-out data, we found that the divergence rate of both gene expression and protein sequences were significantly higher in either high or low morphological diversification groups compared with those in the no morphological diversification group. These results strongly suggest that the divergence of both expression and protein sequence are important sources for morphological diversification of duplicate genes. Although both mechanisms are not mutually exclusive, our analysis suggested that changes of expression pattern play the minor role (33%–41%) and that changes of protein sequence play the major role (59%–67%) in morphological diversification. Finally, we examined to what extent duplicate genes are associated with expression or protein divergence exerting morphological diversification at the whole-genome level. Interestingly, duplicate genes randomly chosen from A. thaliana had not experienced expression or protein divergence that resulted in morphological diversification. These results indicate that most duplicate genes have experienced minor functionalization.