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.

Effect of Exercise on Expression of NeuN and SynapsinI in Cortex and Cognitive Function in Rats after Cerebral Ischemia-reperfusion / 中国康复理论与实践

Objective:To observe the effect of exercise on cognitive function and the expression of NeuN and SynapsinI in prefrontal cortex of rats after cerebral ischemia-reperfusion. Methods:Forty health male Sprague-Dawley rats were randomly divided into sham group (S group, n = 10), model group (M group, n = 10), sham & exercise group (SE group, n = 10) and model & exercise group (ME group, n = 10). The left middle cerebral artery was occluded for one hour and reperfused. SE and ME groups accepted treadmill training, for 14 days. The cognitive function of rats was evaluated with open field experiment and new object recognition experiment. The number and distribution of nerve cells in rat brain were observed with Nissl staining and immunofluorescence staining. The SynapsinI expression in serum was detected with ELISA. Results:Compared with S group, the activity, times of crossing, length and activity time in central area of open field experiment decreased in M group, as well as the cognitive index and length of new object recognition experiment (P < 0.05). Compared with M group, all the indexes increased in ME group (P < 0.05). The number of Nissl bodies decreased in M group (P < 0.05) and the arrangement was disordered, while the number of Nissl bodies increased in ME group (P < 0.05) compared with M group. The NeuN positive cells was more in S group than in M group (P < 0.05), and it was more in ME group than in M group (P < 0.05); as well as that of SynapsinI. The expression of SynapsinI decreased in M group (P < 0.05), and increased in ME group (P < 0.05). Most results of behavioral experiments positively correlated with the expression of Nissl, NeuN and SynapsinI (r > 0.221, P < 0.05). Conclusion:Cerebral ischemia-reperfusion can cause cognitive impairment in rats. Exercise can alleviate nerve injury and improve cognitive function, which may relate to promoting the expression of NeuN and SynapsinI in prefrontal cortex, to increase the number of neurons and synapses.

Global deletion of the RNA decapping enzyme Dcp2 postnatally in male mice results in infertility.

The post-transcriptional regulation of gene expression plays an important role in many essential biological processes. The RNA decapping enzyme Dcp2 is a crucial enzyme involved in RNA degradation. Dcp2 proteins are highly expressed in the testis and brain in adult mice. This study aimed to investigate the in vivo functions of Dcp2. An inducible Dcp2 knockout mouse model was established. No obvious health abnormalities were observed after postnatal global deletion of Dcp2 in male mice. However, Dcp2-deleted male mice were infertile and showed Sertoli cell vacuolization and germ cell degeneration. Dcp2 deletion resulted in testicular atrophy, reduced number of epididymal sperm, and increased apoptosis in seminiferous tubules. However, spermatocyte-specific deletion of Dcp2 did not compromise the fertility. The findings of this study indicated that Dcp2 was important for spermatogenesis and male fertility.

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.

MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development.

The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mice, Dcp2 was undetectable but EGFP was expressed, indicating that Dcp2 mRNA was not completely silenced in adult kidneys. Using luciferase reporter assays, we found that miR-141-3p/200a-3p directly targeted the 3' UTR of Dcp2 mRNA. Overexpression of miR-141-3p and miR-200a-3p downregulated endogenous Dcp2 protein expression. Furthermore, miR-141-3p and miR-200a-3p expression was low in embryonic kidneys but increased dramatically after P10 and was negatively correlated with Dcp2 protein expression during renal development. These results suggest miR-141-3p/200a-3p may be involved in post-transcriptional repression of Dcp2 expression during renal development. ABBREVIATIONS: IRES: internal ribosome entry site; EGFP: enhanced green fluorescent protein; UTR: untranslated region.

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.

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>

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.

Factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer in women with secondary infertility / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with secondary infertility.</p><p><b>METHODS</b>The clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone (GnRH) agonist long protocol, GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged ≥ 40 years.</p><p><b>RESULTS</b>Among 1129 cycles, 376 cases (33.30%) had clinical pregnancy and 753 cases (66.70%) had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups (P<0.05); while only maternal age (OR=0.900, 95% CI: 0.873~0.928, P<0.001) and the number of embryos transferred (OR=2.248, 95% CI: 1.906~2.652, P<0.001) were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged ≥ 40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation (P>0.05).</p><p><b>CONCLUSION</b>Maternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol, GnRH agonist short protocol or GnRH antagonist protocol.</p>

miRNA-1297 induces cell proliferation by targeting phosphatase and tensin homolog in testicular germ cell tumor cells.

To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3'-UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration-dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells.

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.

Effect of nasal cavity expansion surgery on chronic nasal obstructive diseases on the blood supply of the cerebral arterial system / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system.</p><p><b>METHODS</b>Fifty-nine inpatients with abnormal blood supply of cerebral arterial system confirmed by transcranial doppler (TCD) and chronic nasal obstructive diseases were included in this study. All patients accepted nasal cavity expansion surgery and were followed-up with TCD every month after operation until TCD became normal, or up to seven months even if the TCD was still abnormal. SPSS 17.0 software was used to analyze the data.</p><p><b>RESULTS</b>In all 59 patients, there were 164 TCD-abnormal cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries became normal within 1 to 7 months after operation, 8 patients (13.56 %) got better, but 14 patients (23.73 %) did not improve.</p><p><b>CONCLUSIONS</b>Abnormal blood flow of some cerebral arteries was possibly induced by increasing the activation of sympathetic nervous system around the vertebral arterial system, caused by chronic nasal obstruction. Nasal dilatancy surgery can improve the blood supplement of the cerebral arterial system.</p>

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>