Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial / 亚洲男科学杂志(英文版)

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

RNA-Binding Protein MSI2 Binds to miR-301a-3p and Facilitates Its Distribution in Mitochondria of Endothelial Cells.

Numerous miRNAs have been detected in mitochondria, which play important roles in many physiological and pathophysiological processes. However, the dynamic changes of miRNA distribution in mitochondria and their mechanisms in reactive oxygen species (ROS)-induced endothelial injury remain unclear. Therefore, miRNA levels in whole cells and mitochondria of H2O2-treated endothelial cells were analyzed by small RNA sequencing in the present study. The results showed that H2O2 significantly reduced the relative mitochondrial distribution of dozens of miRNAs in human umbilical vein endothelial cells (HUVECs). Among the high-abundance miRNAs, miR-301a-3p has the most significant changes in the redistribution between cytosol and mitochondria confirmed by absolute quantitative polymerase chain reaction (qPCR). To unravel the mechanism of miR-301a-3p distribution in mitochondria, RNA pull-down followed by label-free quantitative proteomic analysis was performed, and RNA-binding protein Musashi RNA binding protein 2 (MSI2) was found to specifically bind to miR-301a-3p. Western blotting and immunofluorescence colocalization assay showed that MSI2 was located in mitochondria of various cell types. H2O2 significantly downregulated MSI2 expression in whole endothelial cells, promoted the distribution of MSI2 in cytosol and decreased its distribution in the mitochondria. Moreover, overexpression of MSI2 increased the mitochondrial distribution of miR-301a-3p, whereas inhibition of MSI2 decreased its distribution in mitochondria. Thus, MSI2 might be responsible for the distribution of miR-301a-3p between cytosol and mitochondria in endothelial cells. Our findings revealed for the first time that MSI2 was involved in the regulation of miRNA distribution in mitochondria and provided valuable insight into the mechanism of mitochondrial distribution of miRNAs.

Audiovisual Sexual Stimulation and RigiScan Test for the Diagnosis of Erectile Dysfunction / 中华医学杂志(英文版)

<p><b>Background</b>Currently available evaluation criteria for penile tumescence and rigidity have been fraught with controversy. In this study, we sought to establish normative Chinese evaluation criteria for penile tumescence and rigidity by utilizing audiovisual sexual stimulation and RigiScan™ test (AVSS-Rigiscan test) with the administration of phosphodiesterase-5 inhibitor.</p><p><b>Methods</b>A total of 1169 patients (aged 18-67 years) complained of erectile dysfunction (ED) underwent AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor. A total of 1078 patients whose final etiological diagnosis was accurate by means of history, endocrine, vascular, and neurological diagnosis, International Index of Erectile Function 5 questionnaire, and erection hardness score were included in the research. Logistic regression model and receiver operating characteristic curve analysis were performed to determine the cutoff value of the RigiScan™ data. Then, the multivariable logistic analysis was used in the selected variables.</p><p><b>Results</b>A normal result is defined as one erection with basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5% and base at least 50.5%, average maximum rigidity of tip at least 62.5% and base at least 67.5%, △tumescence (increase of tumescence or maximum-minimum tumescence) of tip at least 1.75 cm and base at least 1.95 cm, total tumescence time at least 29.75 min, and times of total tumescence at least once. Most importantly, basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5%, and base at least 50.5% would be the new normative Chinese evaluation criteria for penile tumescence and rigidity. By multivariable logistic regression analysis, six significant RigiScan™ parameters including times of total tumescence, duration of erectile episodes over 60%, average event rigidity of tip, △tumescence of tip, average event rigidity of base, and △tumescence of base contribute to the risk model of ED. In logistic regression equation, predict value P < 0.303 was considered as psychogenic ED. The sensitivity and specificity of the AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor in discriminating psychogenic from organic ED was 87.7% and 93.4%, respectively.</p><p><b>Conclusions</b>This study suggests that AVSS-RigiScan test with oral phosphodiesterase-5 inhibitors can objectively assess penile tumescence and rigidity and seems to be a better modality in differentiating psychogenic from organic ED. However, due to the limited sample size, bias cannot be totally excluded.</p>

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients.

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

Urodynamic characteristics of awake rats under retrained versus freely moving condition: Using a novel model / 华中科技大学学报（医学）（英德文版）

Urodynamic investigation in conscious rats is widely employed to explore functional bladder disorders of various etiologies and pathogeneses. Rats can be placed in restraining cages or wide cabinets where they are allowed to move freely during cystometry. However, the requirements of special devices hampered the application of urodynamic test in freely moving rats, and whether the restraint has any effects on urodynamic parameters in conscious rats remains obscure. In the present study, we described a novel approach for urodynamic investigation in both restrained and freely moving conscious rats. In addition, we for the first time systematically compared the urodynamic parameters of rats in the two conditions. With the current method, we successfully recorded stable and repeatable intravesical pressure traces and collected expected reliable data, which supported the idea that the restraint does not affect the activity of the micturition reflex in rats, provided sufficient and appropriate measures could be applied during cystometry. Fewer technique problems were encountered during urodynamic examination in restrained rats than in freely moving ones. Taken together, conscious cystometry in rats placed in restraining cages with proper managements is a reliable and practical approach for evaluating the detrusor activity and bladder function.

miR-206 inhibits renal cell cancer growth by targeting GAK / 华中科技大学学报（医学）（英德文版）

Renal cell cancer (RCC) remains one of the most lethal types of cancer in adults. MicroRNAs (miRNAs) play key roles in the pathogenesis of RCC. The role of miR-206 in RCC has not been fully understood. The purpose of this study was to examine the role of miR-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism. miR-206 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RCC cell lines (786-O and OS-RC-2 cells) and clinical samples. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] method, colony formation and transwell assay were used to detect the tumor-suppressing ability of miR-206 in RCC. Luciferase assay was performed to verify the precise target of miR-206. The results showed that the expression of miR-206 was significantly down-regulated in RCC tissues and cells. The expression level of cyclin G-associated kinase (GAK), a master regulator of tumor proliferation and metastasis, was up-regulated with the decrease in miR-206 in RCC tissues as well as RCC cell lines. In addition, the miR-206 inhibitor promoted the proliferation, migration and invasion of 786-O and OS-RC-2 cells. Bioinformatics combined with luciferase and Western blot assays revealed that miR-206 inhibited the expression of GAK. Moreover, miR-206 regulates RCC cell growth partly through targeting GAK. Our study indicated that miR-206 functions as a tumor suppressor in regulating the proliferation, migration and invasion of RCC by directly targeting GAK, and it holds promises as a potential therapeutic target for RCC.

Urodynamic characteristics of awake rats under retrained versus freely moving condition: Using a novel model / 华中科技大学学报（医学）（英德文版）

Urodynamic investigation in conscious rats is widely employed to explore functional bladder disorders of various etiologies and pathogeneses. Rats can be placed in restraining cages or wide cabinets where they are allowed to move freely during cystometry. However, the requirements of special devices hampered the application of urodynamic test in freely moving rats, and whether the restraint has any effects on urodynamic parameters in conscious rats remains obscure. In the present study, we described a novel approach for urodynamic investigation in both restrained and freely moving conscious rats. In addition, we for the first time systematically compared the urodynamic parameters of rats in the two conditions. With the current method, we successfully recorded stable and repeatable intravesical pressure traces and collected expected reliable data, which supported the idea that the restraint does not affect the activity of the micturition reflex in rats, provided sufficient and appropriate measures could be applied during cystometry. Fewer technique problems were encountered during urodynamic examination in restrained rats than in freely moving ones. Taken together, conscious cystometry in rats placed in restraining cages with proper managements is a reliable and practical approach for evaluating the detrusor activity and bladder function.

Blocking GSK3ß-mediated dynamin1 phosphorylation enhances BDNF-dependent TrkB endocytosis and the protective effects of BDNF in neuronal and mouse models of Alzheimer's disease.

Endocytosis of tropomyosin related kinase B (TrkB) receptors has critical roles in brain-derived neurotrophic factor (BDNF) mediated signal transduction and biological function, however the mechanism that is governing TrkB endocytosis is still not completely understood. In this study, we showed that GSK3ß, a key kinase in neuronal development and survival, could regulate TrkB endocytosis through phosphorylating dynamin1 (Dyn1) but not dynamin2 (Dyn2). Moreover, we found that beta-amyloid (Aß) oligomer exposure could impair BDNF-dependent TrkB endocytosis and Akt activation through enhancing GSK3ß activity in cultured hippocampal neurons, which suggested that BDNF-induced TrkB endocytosis and the subsequent signaling were impaired in neuronal model of Alzheimer's disease (AD). Notably, we found that inhibiting GSK3ß phosphorylating Dyn1 by using TAT-Dyn1SpS could rescue the impaired TrkB endocytosis and Akt activation upon BDNF stimuli under Aß exposure. Finally, TAT-Dyn1SpS could facilitate BDNF-mediated neuronal survival and cognitive enhancement in mouse models of AD. These results clarified a role of GSK3ß in BDNF-dependent TrkB endocytosis and the subsequent signaling, and provided a potential new strategy by inhibiting GSK3ß-induced Dyn1 phosphorylation for AD treatment.

Prognostic significance of lymphovascular invasion in bladder cancer after surgical resection: A meta-analysis / 华中科技大学学报（医学）（英德文版）

Bladder cancer remains a commonly diagnosed malignancy worldwide, bringing huge economic burden and high morbidity for patients. Assessment of prognostic significance of lymphovascular invasion (LVI) is a critical issue in the surgical management of bladder cancer after transurethral resection or radical cystectomy. A systematic search of PubMed, Embase and Cochrane Library was performed up to Oct 10, 2014 to identify eligible studies. Outcomes of interest were collected from studies comparing overall survival (OS), cancer specific survival (CSS) and recurrence free survival (RFS) in patients with the LVI. Results of studies were pooled, and combined hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for survival were used as the effect size estimation. Funnel plots were done to show the publication bias, while the forest plots and subgroup analyses were used to limit the heterogeneity. A total of 20 studies (10 663 patients) met the eligibility criteria and were included for this meta-analysis. Our pooled results showed that there were significant differences in OS (pooled HR, 1.71; 95%CI, 1.52-1.92; P<0.00001), CSS (pooled HR, 2.25; 95% CI, 1.80-2.81; P<0.00001) and RFS (pooled HR, 1.91; 95% CI, 1.57-2.32; P<0.00001) between the patients with LVI and the patients without LVI. There were significant heterogeneities observed in the studies concerning the relationship between LVI and CSS, RFS. There was no clear evidence of publication bias. When tumor stage was beyond T3, LVI lost its predictive value for CSS and RFS. For the patients who had negative lymph nodes, LVI was still an adverse predictor. Our pooled results demonstrate that LVI indicates poor prognosis of patients with bladder cancer after surgical procedures, and it can be of particular importance in clinical practice. However, these results need to be further confirmed by more adequately designed prospective studies.

Androgen may improve erectile function in castrated rats by regulating the ERK1/2 pathway / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway in erectile dysfunction (ED) caused by the absence of testosterone (T).</p><p><b>METHODS</b>We randomly divided 30 eight-week-old healthy male SD rats into groups A (control) , B (castration), and C (castration + androgen replacement). The rats in groups B and C were castrated surgically, and those in C injected with T undecanoate (100 mg/kg) at 1 week after castration, while the others with 0.9% normal saline instead. At 1 month after treatment, we determined the serum T level, intracavernous pressure (ICP), and mean carotid arterial pressure (MAP) of the rats, and detected the expressions of ERK1/2 and endothelial nitric oxide synthase (eNOS) by Western blot.</p><p><b>RESULTS</b>The serum T level was significantly lower in group B ([1.27 ± 0.48] nmol/L) than in A ([17.14 ± 1.07] nmol/L) and C ([16.24 ± 1.90] nmol/L) (P < 0.05), and so were ICP and MAP (P < 0.05). The expression of ERK1/2 showed no statistically significant differences among the three groups (P > 0.05), that of phosphatase ERK1/2 was markedly higher while that of eNOS remarkably lower in group B than in A and C (both P < 0.05).</p><p><b>CONCLUSION</b>Androgen replacement may improve the erectile function of castrated rats by regulating the ERK1/2 pathway.</p>

Long noncoding RNAs in prostate cancer / 中华男科学杂志

Long non-coding RNAs (lncRNAs) are a group of RNA molecules which are longer than 200 nucleotides. They do not have functional open reading frames and cannot encode proteins. Recent studies have demonstrated that lncRNAs are widely involved in the regulation of gene expression network at epigenetic, transcriptional and post-transcriptional levels, which may affect the growth, proliferation, differentiation, metabolism, apoptosis and other important physiological processes of cells. The abnormal expression of lncRNAs is closely associated with the development, invasion, metastasis and prognosis of tumors. The development of prostate cancer is a multi-factor and multi-step process, in which abnormal gene expression may play an important role. This review focuses on the recent progress in the studies on the role of lncRNAs in prostate cancer, aiming for some new clues to the clinical prevention, diagnosis and treatment of this malignancy.

Efficacy of immediate instillation combined with regular instillations of pirarubicin for Ta and T1 transitional cell bladder cancer after transurethral resection: a prospective, randomized, multicenter study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immediate intravesical instillation of chemotherapeutic agents after transurethral resection (TUR) of nonmuscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin (THP(®)) as prophylaxis compared to regular instillations only after TUR operation.</p><p><b>METHODS</b>This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer (Ta and T1) pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP(®) once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only.</p><p><b>RESULTS</b>A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group (14.3%; P = 0.042). Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group (6.8%) than in the control group (14.0%; P = 0.047), although no significant differences were found in high-risk patients.</p><p><b>CONCLUSION</b>One immediate dose of THP(®) 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.</p>

Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Over-expression of LRIG3 suppresses growth and invasion of bladder cancer cells / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the impact of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological features of bladder cancer cell lines. The plasmids of over-expressed LRIG3 and the blank plasmid serving as control were transfected into the bladder cancer cell lines, T24, EJ and BIU-87, and the expression levels of LRIG3 mRNA and protein were detected by using real-time PCR and Western blotting. The changes in the cell cycle and apoptosis were examined by using flow cytometry. The invasive ability was measured by Transwell assay, and CCK-8 assays were used to measure the proliferation of cells. As compared with the control group, the LRIG3 mRNA and protein expression levels in LRIG3 cDNA-transfected group were raised significantly (P<0.05). The average number of cells with up-regulated LRIG3 passing through the inserted filter was decreased significantly as compared with the control group (P<0.05). Up-regulation of LRIG3 also could inhibit proliferation and induce apoptosis of T24, EJ and BIU-87 cells. Except BIU-87, the T24 and EJ cells transfected with LIRG3 cDNA were arrested in G(0)/G(1) phase compared to the control group (P<0.05). In conclusion, the over-expression of LRIG3 could influence the cell cycle and invasion, inhibit proliferation and induce apoptosis in the three bladder cancer cell lines.

Over-expression of LRIG3 suppresses growth and invasion of bladder cancer cells / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the impact of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological features of bladder cancer cell lines. The plasmids of over-expressed LRIG3 and the blank plasmid serving as control were transfected into the bladder cancer cell lines, T24, EJ and BIU-87, and the expression levels of LRIG3 mRNA and protein were detected by using real-time PCR and Western blotting. The changes in the cell cycle and apoptosis were examined by using flow cytometry. The invasive ability was measured by Transwell assay, and CCK-8 assays were used to measure the proliferation of cells. As compared with the control group, the LRIG3 mRNA and protein expression levels in LRIG3 cDNA-transfected group were raised significantly (P<0.05). The average number of cells with up-regulated LRIG3 passing through the inserted filter was decreased significantly as compared with the control group (P<0.05). Up-regulation of LRIG3 also could inhibit proliferation and induce apoptosis of T24, EJ and BIU-87 cells. Except BIU-87, the T24 and EJ cells transfected with LIRG3 cDNA were arrested in G(0)/G(1) phase compared to the control group (P<0.05). In conclusion, the over-expression of LRIG3 could influence the cell cycle and invasion, inhibit proliferation and induce apoptosis in the three bladder cancer cell lines.

Does urothelial cancer of bladder behave differently in young patients? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.</p><p><b>METHODS</b>From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.</p><p><b>RESULTS</b>Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.</p><p><b>CONCLUSIONS</b>Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.</p>

Extracorporeal shock wave treatment for non-inflammatory chronic pelvic pain syndrome: a prospective, randomized and sham-controlled study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a clinical syndrome characterized by pain in the perineum, pelvis, suprapubic area, or external genitalia and variable degrees of voiding and ejaculatory disturbance. The analgesic effect of extracorporeal shock wave treatment (ESWT) was an interesting phenomenon with an unclear mechanism discovered by chance in the applications for urolithiasis, on which ESWT has become an increasingly popular therapeutic approach as an alternative option for the treatment of a number of soft tissue complaints. In this study, we aimed to evaluate the feasibility and efficacy of ESWT in non-inflammatory (IIIB) CP/CPPS.</p><p><b>METHODS</b>Men diagnosed with IIIB CP/CPPS were randomized to either ESWT (group 1, n = 40) or the control (group 2, n = 40). Group 1 received 20 000 shock wave impulses in 10 sessions over a two-week period, whereas group 2 received only a sham procedure. The total scores and sub-domain scores of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) for both groups were assessed at baseline, mid-treatment, end-point, and 4-week and 12-week follow-up visits.</p><p><b>RESULTS</b>The mean total NIH-CPSI score of group 1 was significantly decreased from baseline at all post-treatment time points (P < 0.01 for all). Decreases in pain domain and quality of life (QOL) scores were also significant. In group 2, no significant decreases of total NIH-CPSI score and pain domain score were found at all post-treatment time points. At the end-point of treatment, 71.1% of group 1 exhibited perceptible improvement in total NIH-CPSI compared with 27.0% of group 2 (P < 0.001); additionally, 28.9% of group 1 exhibited clinically significant improvement compared with 10.8% of group 2 (P < 0.01). Moreover, a greater number of patients in group 1 at 4-week and 12-week follow-up were rated as responders (perceptible and clinically significant response) compared with group 2.</p><p><b>CONCLUSION</b>ESWT exhibits a potentially therapeutic role in the treatment of CP/CPPS.</p>

Screening of differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Idiopathic hyperoxaluria (IH) may be caused by increased endogenous formation or exogenous absorption of oxalic acid. Characterization of the molecular pathogenesis of IH has been hampered by the lack of an ideal animal model. We therefore established a stabile rat IH model in order to analyze variation in gene expression profile in the jejunum and to investigate the association between IH pathogenesis and exogenous absorption of oxalic acid.</p><p><b>METHODS</b>A rat model of IH was established and three female rats with IH were assigned to the study group, while three normal rats served as controls. Total RNA was isolated from the jejunum of rats in the two groups and mRNA was purified, reversely transcribed, labeled with Cy5 or Cy3 and hybridized to 27K Rat Genome Array. Differences in gene expression profile between the 2 groups were analyzed by bioinformatics methods.</p><p><b>RESULTS</b>Comparative analysis revealed that the expression of 517 genes was up-regulated and that of 203 genes was down-regulated by at least two-fold in the jejunum of rats with idiopathic hyperoxaluria. These genes are related to many functions including cell signal transduction, DNA binding and transcription, ATP binding, ion binding and transport, cell receptors, immunity, cyclins, cytoskeleton structure, and metabolic proteins. Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis revealed that the variations of 239 pathway functional changes are statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>cDNA microarray can be used effectively to screen differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria. These differentially expressed genes may underlie idiopathic hyperoxaluria pathophysiology and provide a platform for further studying molecular pathogenetic mechanisms.</p>

Levels of cytokines and heat-shock protein 70 in the seminal plasma of patients with chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the diagnostic value and potentially protective capacity of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta) and heat-shock protein 70 (HSP70) in chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).</p><p><b>METHODS</b>We determined the levels of cytokines TNF-alpha, IL-1beta and HSP70 by ELISA in the seminal plasma of 150 men: 36 with CBP, 43 with CP/CPPS IIIA, 46 with CP/CPPS IIIB, and 25 healthy controls. We analyzed the correlation of the HSP70 expression in the CBP and CP/CPPS patients with the chronic prostatitis symptom index (CPSI).</p><p><b>RESULTS</b>Significantly increased levels of TNF-alpha, IL-1beta and HSP70 were observed in the seminal plasma of the CBP patients as compared with the CP/CPPS patients and healthy controls. The expression of IL-1beta was significantly higher in the patients with CP/CPPS IIIA than in those with CP/CPPS III B and the controls, while the HSP70 level remarkably lower in those with CP/CPPS than in the controls, and its concentration in the seminal plasma of the CBP patients was negatively correlated with CPSI.</p><p><b>CONCLUSION</b>The levels of HSP70 and IL-1beta in the seminal plasma appear to be most reliable molecular biological markers for the diagnosis of CBP and CP/CPPS, respectively. HSP7O has an important protective role in the regulation of cell functions in CBP patients. CP/CPPS is probably detrimental to the function of T cells and consequently suppresses the expression of HSP70.</p>