Efficacy and safety of dapoxetine for premature ejaculation: an updated systematic review and meta-analysis.

We conducted a systematic review and meta-analysis of published randomised controlled trials of dapoxetine for premature ejaculation. We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov and Clinical Trials.gov for studies reporting dapoxetine in men with premature ejaculation. Efficacy endpoints included intravaginal ejaculatory latency times (IELT), personal distress related to ejaculation (PDRE) and treatment-emergent adverse events (TEAEs) was used to evaluate safety. Data were analysed using a random-effects model. Electronic search identified 276 papers. The final analysis included eight papers (n = 8422 subjects). Analysis of the pooled results indicated efficacy in both IELT (weighted mean difference (WMD) = 1.67, 95% confidence interval (CI) 1.45-1.89) and PDRE (relative risk = 1.26, 95% CI 1.18-1.35). Subgroup analysis indicated efficacy (i.e. increase in IELT) for 30- and 60-mg on-demand dapoxetine (WMD 1.38 (95% CI 1.01-1.75) and 1.62 (95% CI 1.40-1.84) respectively), as well as daily use of 60 mg dapoxetine (WMD 2.18, 95% CI 1.71-2.64). The safety profile was acceptable. Based on the different effects of magnitude of the three dosing regimens, we recommend a stepwise approach, starting with 30 mg on demand, then 60 mg on demand and finally 60 mg dapoxetine daily.

[Impacts of Chk1 and Chk2 gene expressions on sperm concentration and motility].

OBJECTIVE: To study the correlation of the gene expressions of Chk1 and Chk2 with sperm concentration and motility. METHODS: According to sperm concentration and motility (percentage of progressively motile sperm), we divided 80 semen samples into four groups of equal number: normal control, oligozoospermia (OS), asthenospermia (AS), and oligoasthenozoospermia (OAS). We detected the sperm DNA fragmentation index (DFI) and viability and determined the expressions of Chk1 and Chk2 in the sperm by RT-PCR and Western blot. RESULTS: Statistically significant differences were not found in sperm DFI among the control, OS, AS, and OAS groups (21.24±6.93, 19.67±7.64, 21.52±6.92, and 19.28±11.55, P>0.05), but observed in sperm concentration, progressive motility, and viability between the DFI >30% and DFI ≤30% groups (P<0.01). Compared with the normal control, sperm viability was remarkably decreased in the OS, AS, and OAS groups (ï¼»83.48±9.87ï¼½% vs ï¼»63.86±9.16ï¼½%, ï¼»50.45±16.99ï¼½%, and ï¼»39.21±15.74ï¼½%, P<0.05). RT-PCR showed remarkable differences among the control, OS, AS, and OAS groups in the relative expression level of Chk1 mRNA (0.73±0.22, 0.62±0.14, 1.03±0.39, and 0.92±0.071, P<0.01), which was correlated positively with sperm concentration (b = 80.661, P<0.01) but negatively with sperm motility (b = －19.275, P < 0.01), as well as in that of Chk2 mRNA (0.66±0.30, 0.27±0.09, 0.59±0.19, and 0.42 ± 0.11, P<0.01), which was correlated negatively with sperm concentration (b = －90.809, P<0.01) but positively with sperm motility (b = 27.507, P <0.01). The relative expression levels of the Chk1 protein were significantly different among the four groups (0.63±0.05, 0.42±0.03, 1.13±0.08, and 0.87±0.07, P<0.01), which was correlated positively with sperm concentration (b = 55.74, P<0.01) but negatively with sperm motility (b =－22.649, P<0.01), and so were those of the Chk2 protein (1.23±0.36, 0.37±0.16, 0.87±0.08, and 0.68±0.12, P<0.01), which was correlated negatively with sperm concentration (b =－53.001, P<0.01) but positively with sperm motility (b = 16.676, P < 0.01). CONCLUSIONS: Chk1 and Chk2 are significantly expressed in human sperm. In case of sperm DNA damage, up-regulated Chk1 expression may enhance sperm apoptosis and lead to asthenospermia, while increased Chk2 expression may inhibit spermatogenesis and result in oligospermia.

[Safety and effect of transurethral holmium laser enucleation of the prostate versus bipolar transurethral plasmakinetic prostatectomy for benign prostatic hyperplasia: A meta-analysis].

OBJECTIVE: To evaluate the safety and effect of transurethral holmium laser enucleation of the prostate (HoLEP) in comparison with bipolar transurethral plasmakinetic prostatectomy (TUPKP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: We searched the databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP, and Wangfang Data for controlled clinical trials about HoLEP versus TUPKP in the treatment of BPH published up to April 2016. The studies were screened according to the inclusion and exclusion criteria, the data extracted, and their quality evaluated by 2 reviewers independently, followed by a meta-analysis using the RevMan 5.3 software. RESULTS: A total of 7 studies were included, involving 2031 cases. In comparison with TUPKP, HoLEP showed significantly longer operation time (WMD = 24.61, 95% CI 11.88, 37.34, P lt; 0.001), shorter hospital stay (WMD =－1.91, 95% CI －3.74, －0.07, P = 0.04), shorter bladder irrigation time (WMD = －21.50, 95% CI －34.95, －8.06, P = 0.002), shorter catheter-indwelling time (WMD = －27.60, 95% CI －48.17, －7.03, P = 0.009), less hemoglobin loss (WMD = － 0.42, 95% CI －0.78, －0.07, P = 0.02); lower postvoid residual urine (PVR) at 3 months (WMD = －3.35, 95% CI －4.46, －2.23, P<0.001) and 6 months after surgery (WMD =－1.11, 95% CI －2.18, －0.05, P = 0.04); higher maximum urinary flow rate (Qmax) (WMD = 0.42, 95% CI 0.04, 0.80, P = 0.03) and fewer urinary tract irritation symptoms (OR =0.58, 95% CI 0.41, 0.81, P = 0.002) at 12 months after surgery. No statistically significant differences were found between the two groups in the volume of resected tissue, serum sodium reduction, urethral stricture, erectile dysfunction, retrograde ejaculation, or transient urinary incontinence (P>0.05), or in the improvement of the quality of life (QoL) at 1, 3 and 12 months, International Prostate Symptom Score (IPSS) at 1, 3, 6 and 12 months, Qmax at 1, 3 and 6 months, or International Index of Erectile Function-5 (IIEF-5) at 6 months after surgery (P>0.05). CONCLUSIONS: HoLEP is preferred to TUPKP in clinical application for its advantages of higher Qmax at 12 months after surgery, lower PVR at 3 and 6 months, higher peri-operative safety, faster recovery, and fewer urinary tract irritation symptoms. However, for the quantity and quality limitations of the included publications, our findings are to be further supported by large-sample, multi-center, and high-quality prospective controlled clinical studies.

[Tea polyphenols reduces the apoptosis of spermatogenic cells in rats with experimental varicocele].

OBJECTIVE: To study the effect of tea polyphenols (TP) on the apoptosis of germ cells in rats with experimental varicocele. METHODS: Thirty-two adolescent male Wistar rats were randomly and equally divided into groups A (sham-operation), B (high-dose TP), C (low-dose TP), and D (experimental left varicocele). Experimental varicocele was induced by partial ligation of the left renal vein in the latter three groups of rats. The animals in groups A and D were fed with normal saline, while those in B and C with TP at 40 and 10 mg per kg per d, respectively, all for 4 weeks. Then, all the rats were sacrificed and the left testes harvested for determination of the expression of HIF-1, Bcl-2, Bax, CytC, and caspase-3 by immunohistochemistry and measurement of the apoptosis index (AI) of spermatogenic cells. RESULTS: The expression of Bcl-2 was higher in groups B and C than in D but lower than in A (P < 0.05), and lower in C than in B (P < 0.05). However, the expressions of HIF-1, Bax, CytC, and caspase-3 were lower in groups B and C than in D but higher than in A (P < 0.05), and higher in C than in B (P < 0.05). The AI of spermatogenic cells was the lowest in group A, higher in D than in the other groups but lower in B than in C (P < 0.05). CONCLUSION: TP can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in varicocele rats.

Macroscale preparation of CoS2 nanoparticles for ultra-high fast-charging performance in sodium-ion batteries.

Improving the fast-charging capabilities and energy storage capacity of electric vehicles presents a feasible strategy for mitigating the prevalent concern of range anxiety in the market. Nanostructure electrode materials play a crucial role in this process. However, the current method of preparation is arduous and yields restricted quantities. In view of this, we have devised an innovative approach that provides convenience and efficacy, facilitating the large-scale synthesis of CoS2 nanoparticles, which exhibited exceptional performance. When the current density was 1000 mA g-1, the discharging capacity reached 760 mAh g-1 after 400 cycles. Remarkably, even at an increased current density of 5000 mA g-1, the discharging capacity of CoS2 remained at 685.5 mAh g-1. The ultra-high performance could be attributed to the specific surface area, which minimized the diffusion distance of sodium-ions during the charging and discharging processes and mitigated the extent of structural damage. Our straightforward preparation techniques facilitate the mass production and present a novel approach for the development of cost-effective and high-performing anode materials for sodium-ion batteries.

[Tea polyphenols protects the testis following testicular torsion/detorsion in rats].

OBJECTIVE: To investigate the protective effect of tea polyphenols against testis injury induced by unilateral testicular torsion/detorsion. METHODS: Twenty-four healthy male Wistar rats were equally randomized into Group I, sham operation, and Groups II and III, subjected to left lateral 720 degrees testicular torsion, followed by detorsion at 6 hours. Intraperitoneal injection of isotonic saline and polyphenols was initiated 30 minutes prior to detorsion and maintained at a low dose for 3 days postoperatively. All the rats were fed under the same condition and sacrificed 5 days later, the left torsional testes harvested for the detection of the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and the apoptosis of spermatogenic cells by TUNEL. RESULTS: Significant differences were observed among Groups I, I and III in the levels of SOD in the left torsional testes ([285.00 +/- 22.51], [242.00 +/- 17.62] and [261.00 +/- 10.01] nU/mg, P < 0.05), as well as in the levels of MDA ([1.81 +/- 0.20], [4.34 +/- 0.34] and [2.94 +/- 0.38] nU/mg, P < 0.05). And the apoptosis indexes of spermatogenic cells were 6.64 +/- 1.82, 55.23 +/- 6.46 and 31.84 +/- 5.56 in the three groups, significantly reduced in Group III as compared with Group II (P < 0.05). CONCLUSION: Tea polyphenols has a protective effect against testicular torsion-induced ischemic reperfusion injury in rats.

KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo.

PURPOSE: To evaluate the expression in human clear cell renal cell carcinoma (ccRCC) tissues and explore the effects of kinesin family member 4A (KIF4A) on ccRCC progression. METHODS: GEPIA was used to evaluate the mRNA levels of KIF4A in human ccRCC tissues from TCGA database, and Immunohistochemistry (IHC) assays were performed to assess its expression in human ccRCC tissues collected in our hospital. The clinical-pathological analysis was performed to explore the correlation with KIF4A expression. The effects of KIF4A on ccRCC cell proliferation were detected through colony formation and MTT assays. Finally, the effects of KIF4A on tumor growth were measured using a mice model. RESULTS: Bioinformation results showed the expression of KIF4A mRNA was upregulated in ccRCC tissues and high expression of KIF4A was related with poor prognosis in ccRCC patients. We also found a high expression of KIF4A in human ccRCC tissues collected in our hospital. We also found its expression level was correlated with clinical characteristics, including T stage (P=0.035*) and lymphatic metastasis (P=0.028*). We further confirmed that knockdown of KIF4A suppressed cell proliferation in HTB-47 and CRL-1932 cells. Furthermore, KIF4A contributes to tumor growth of ccRCC cells in mice. CONCLUSION: We found the abnormal high expression of KIF4A in human ccRCC tissues and demonstrated that KIF4A could serve as a tumor induction gene.

A potential skin substitute constructed with hEGF gene modified HaCaT cells for treatment of burn wounds in a rat model.

This study aimed to investigate the feasibility of using an immortal keratinocyte cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a skin substitute to treat burn wounds. The skin equivalent was constructed with human EGF (hEGF) gene modified HaCaT cells obtained through stable gene transfection; these were applied to full thickness burn wounds in a rat model. The results showed that the hEGF gene modified HaCaT cells produced more than 390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-ß1 as keratinocyte differentiation markers were elevated in the hEGF gene modified HaCaT cells which were shown to be non-tumorigenic. The skin equivalent constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal morphogenesis with a thick and compact epidermis. Wound healing was accelerated noticeably when applied with this skin substitute seeded with hEGF gene modified HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene might be promising seed cells for construction of genetically modified skin substitute which can effectively secrete hEGF to accelerate wound repair and regeneration.

[Biological effects of paracrine from insulin stimulated adipose-derived stem cells (ADSC) on human vascular endothelial cells].

OBJECTIVE: To study the biological effects of the paracrine from ADSC after being stimulated by insulin on vascular endothelial cells. METHODS: (1) ADSC was isolated from human adipose tissue and cultured in vitro. The third generation cells were collected and divided into insulin group (I, cultured with serum-free DMEM containing 1 x 10(-7) mol/L insulin) and control group (C, cultured with serum-free DMEM) according to the random number table, with 6 slots in each group. Three days later, ADSC culture medium (ADSC-CM) was collected for determination of levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by ELISA. (2) Human umbilical vein endothelial cells (HUVEC) were cultured to the third generation, and they were cultured with special nutrient solution and divided into ADSC-CM with insulin stimulation group (AI), ADSC-CM without insulin stimulation group (AC), insulin group (I, with same concentration as above), blank control group (BC) according to the random number table. Three days later, proliferation of HUVEC was determined with MTT method (with expression of absorbance value). Another two samples of HUVEC were respectively divided into 4 groups as above for determination of apoptosis rate with Annexin V/FITC double-staining 12 hours after culture, and HUVEC migration with scratch adhesion test at post scratch hour (PSH) 12, 24, 36, 48. Data were processed with t test. RESULTS: (1) Compared with those in C group [(287 +/- 47), (577 +/- 84) pg/mL, respectively], the secretion levels of VEGF and HGF in I group [(643 +/- 64), (930 +/- 68) pg/mL, respectively] were significantly increased (with t value respectively 18.869, 18.475, P values all below 0.05). (2) The absorbance value of HUVEC in AI and AC groups was 0.847 +/- 0.042, 0.798 +/- 0.022, respectively, which were higher than that in I and BC groups [0.665 +/- 0.028 (with t value respectively 4.579, 3.732), 0.674 +/- 0.031 (with t value respectively 3.761, 4.073), P values all below 0.01], and that in AI group was higher than that in AC group (t = 2.576, P < 0.05). The apoptosis rates of HUVEC in AI and AC groups [(5.8 +/- 1.9)%, (9.0 +/- 2.0)%, respectively] were obviously lower as compared with that in I and BC groups [(30.4 +/- 6.0)% (with t value respectively 12.891, 10.417), (31.4 +/- 7.4)% (with t value respectively 11.474, 9.783), P values all below 0.05 ], and that in AC group was higher than that in AI group (t = 8.548, P < 0.05). The distance of migration of HUVEC in AI and AC groups were greater than that in I and BC groups at PSH 36, 48, and that in AI group was greater as compared with that in AC group (with t value respectively 4.076, 4.573, P values all below 0.05). CONCLUSIONS: Paracrine from ADSC after being stimulated by insulin can promote proliferation and migration of HUVEC, and suppress its apoptosis, and it is beneficial for tissue vascularization.

Smad interacting protein 1 as a regulator of skin fibrosis in pathological scars.

Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by the excessive and abnormal deposition of collagen-based extracellular matrix (ECM) components. However, the molecular basis of keloid and hypertrophic scar formation has not been fully elucidated. Here, we demonstrated that down-regulation of the transcription factor Smad interacting protein 1 (SIP1) could be relevant to keloid and hypertrophic scar formation. The results of the present study show that the level of SIP1 mRNA is significantly decreased in pathological scar tissues and in normal skin and pathological scar fibroblasts treated with transforming growth factor ß1 (TGF-ß1). In contrast, the expression of SIP1 mRNA is not decreased in normotrophic scar samples. The SIP1 mRNA level inversely correlates with the mRNA level of type I collagen (COL1A2) and directly correlates with the mRNA level of matrix metalloproteinase-1 (MMP1). Overexpression of SIP1 in keloid and hypertrophic scar fibroblasts represses TGF-ß1-stimulated COL1A2 expression and induces MMP1 expression. Alternatively, knockdown of SIP1 in normal skin fibroblasts enhance TGF-ß1-induced COL1A2 levels. These findings suggest that SIP1 could be a regulator of skin fibrosis, and depletion of SIP1 in pathological scar tissues could result in an up-regulation of collagen and down-regulation of matrix metalloproteinase, leading to an abnormal accumulation of ECM along with fibrosis and pathological scar formation.