Impact of cognitive behavioral therapy on premature ejaculation patients: A prospective, randomized controlled trial protocol.

BACKGROUND: Premature ejaculation (PE) is one of the most common male sexual dysfunctions, with a prevalence of about 4%-39% in the Chinese population. Studies have shown that a variety of biological factors can lead to premature ejaculation, such as central nervous system disorders, hypersensitivity of the penis head, and psychological factors. Based on clinical experience, psychological counseling and education of patients and partners should be ranked as the first priority when treating PE. Cognitive behavioral therapy (CBT) addresses emotional, behavioral, and cognitive disorders by altering beliefs and actions. It has also been demonstrated to be clinically useful in treating a number of diseases. The purpose of this trial is to evaluate the efficacy of a mobile-based CBT intervention on patients with PE compared to conventional routine treatment. METHODS: This study is a prospective randomized controlled trial that will be conducted from May 2023 to Dec 2024 at ten hospitals, primarily including the First Affiliated Hospital of Sun Yat-sen University with an 8-week follow-up. The clinical trial central randomization system will be used to create and implement the specific randomization method. Baseline data of both groups will be measured and collected. The premature ejaculation diagnostic tool (PEDT) and the female sexual distress scale-revised for premature ejaculation (FSDS-R-PE) will be collected on the first day, 28±2 days, and 56±2 days during the intervention period, and the intravaginal ejaculatory latency time (IELT) will be measured in both groups. The Shapiro-Wilk test will be used for normality testing. Pearson correlation analysis will be used for correlation analysis. Differences between groups will be compared using analysis of variance or exact probability calculations. DISCUSSION: This study will investigate the effect of a mobile-based CBT intervention on patients with PE. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070581).

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study.

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

Combination of High Ligation and Intraoperative Embolization using Polidocanol for Treatment of Varicoceles.

Varicoceles are dilated veins within the pampiniform plexus and are relatively common in the general male population. The spermatic vein has many branches in the scrotal segment and then gradually merges into 1-2 trunks after passing through the internal inguinal ring. The key to a successful varicocelectomy is to ligate all the spermatic veins while protecting the testicular arteries and spermatic lymphatic vessels from damage. The small veins, including the branches of spermatic veins and collateral veins, are easily missed for ligation during conventional high ligation of varicocele, which has been suggested as a major cause of postoperative recurrence. Although microsurgery effectively reduces the risk of missing ligation of the spermatic veins during surgery, it has several shortcomings, such as long operation time and a steep learning curve. More importantly, this technique is difficult to carry out in primary hospitals due to the requirement of specialized equipment. Therefore, an attempt to modify the traditional high ligation aiming to reduce the postoperative recurrence rate has been carried out here. The protocol here combines traditional high ligation with intraoperative embolization to seal off the branches of the spermatic vein and collateral veins. We rapidly injected foamed sclerosant into the internal spermatic vein under direct observation after separation of the spermatic vein and then ligated all the veins. The foamed sclerosant through the varicose vein hampers endothelial cell growth, promotes the growth of thrombus and fibrosis, and ultimately forms fibrous streaks that permanently fill the venous. The results showed a more satisfactory effect on reducing the postoperative recurrence rate compared with traditional high ligation. Since this protocol is simple to carry out and has better results in reducing the recurrence rate, this can be an alternative surgical method for the treatment of varicocele, especially in primary hospitals.

[Impact of lipopolysaccharide-induced inflammation on sperm quality in male rats and its possible mechanisms].

OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS)-induced inflammation on sperm quality in male rats and its possible mechanisms. METHODS: Thirty-six male SD rats were randomly divided into groups A (control), B (12 h LPS), C (24 h LPS) and D (72 h LPS), the former group injected intraperitoneally with sterile saline, and the latter three with LPS at 5 mg/kg and sacrificed at 12, 24 and 72 hours respectively after treatment. Then the left epididymides of the rats were harvested for detection of the sperm count and motility in the cauda epididymis, measurement of the relative sperm count value, examined the content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in the epididymal plasma, and determined the apoptosis rate of spermatogenic cells by flow cytometry (FCM). RESULTS: Compared with the parameters in group A, sperm motility in the cauda epididymis was decreased in groups B (ï¼»68.01 ± 1.80ï¼½% vs ï¼»62.28 ± 4.06ï¼½%, P < 0.05), C (ï¼»68.01 ± 1.80ï¼½% vs ï¼»45.35 ± 3.39ï¼½%, P < 0.05) and D (ï¼»68.01 ± 1.80ï¼½% vs ï¼»34.85 ± 4.42ï¼½%, P < 0.01), and so was the sperm count in the cauda epididymis (ï¼»38.94 ± 4.08ï¼½ vs ï¼»37.15 ± 2.54ï¼½ ×106/ 100 mg, P > 0.05; ï¼»38.94 ± 4.08ï¼½ vs ï¼»31.97 ± 2.81ï¼½ ×106/ 100 mg, P < 0.05; ï¼»38.94 ± 4.08ï¼½ vs ï¼»28.60 ± 4.03ï¼½ ×106/ 100 mg, P < 0.01), while the content of MDA in the epididymal plasma significantly increased (ï¼»4.66 ± 1.49ï¼½ vs ï¼»15.95 ± 3.26ï¼½ nmol/mg prot, P < 0.01; ï¼»4.66 ± 1.49ï¼½ vs ï¼»12.93 ± 2.54ï¼½ nmol/mg prot, P < 0.01; ï¼»4.66 ± 1.49ï¼½ vs ï¼»9.67 ± 1.68ï¼½ nmol/mg prot, P < 0.05), the activity of SOD reduced (ï¼»879.335 ± 105.089ï¼½ vs ï¼»729.265 ± 93.783ï¼½ U/mg prot, P > 0.05; ï¼»879.335 ± 105.089ï¼½ vs ï¼»694.126 ± 58.530ï¼½ U/mg prot, P < 0.05; ï¼»879.335 ± 105.089ï¼½ vs ï¼»655.352 ± 115.215ï¼½ U/mg prot, P < 0.05), and the apoptosis rate of spermatogenic cells dramatically elevated (ï¼»4.21 ± 1.67ï¼½% vs ï¼»11.01 ± 3.30ï¼½%, P < 0.05; ï¼»4.21 ± 1.67ï¼½% vs ï¼»23.88 ± 4.58ï¼½%, P < 0.01; ï¼»4.21 ± 1.67ï¼½% vs ï¼»41.28 ± 2.28ï¼½%, P < 0.01). CONCLUSION: LPS-induced inflammation damages spermatogenic cells and the quality of epididymal sperm in male rats in a time-dependent manner, which is associated with oxidative stress injury and cell apoptosis in the reproductive system.

[Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows for premature ejaculation: A prospective single-center randomized controlled study].

OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistad) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.

[Transcutaneous electrical acupoint stimulation improves pregnancy outcomes of in vitro fertilization- embryo transfer : A meta-analysis of randomized controlled trials].

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to February 2021 for published randomized controlled trials (RCT) relevant to TEAS for the improvement of the pregnancy outcomes of IVF-ET. We performed literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria, followed by a meta-analysis with the RevMan 5.3 software. RESULTS: A total of 2 206 cases of IVF-ET from 9 RCTs were included, 1 018 in the TEAS group and 1 188 in the control. The clinical pregnancy rate was significantly higher in the TEAS than in the mock TEAS and non-TEAS control groups (RR = 1.85, 95% CI: 1.42－2.42, P < 0.001; RR = 1.23, 95% CI: 1.10－1.39, P = 0.0004), and so was it before and after oocyte retrieval (RR = 1.50, 95% CI: 1.03－2.17, P = 0.03; RR = 1.47, 95% CI: 1.12－1.92, P = 0.005). The TEAS group also showed dramatically improved embryo implantation rate (RR = 1.49, 95% CI: 1.24－1.79, P < 0.0001) and live birth rate (RR = 1.44, 95% CI: 1.04－1.98, P = 0.03) compared with the control. CONCLUSIONS: As a safe and non-invasive treatment, TEAS can significantly improve the pregnancy outcomes of IVF-ET, with definite effectiveness. /.

Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells.

circRNAs are present in human ovarian tissue, but how they regulate ovarian function remains unknown. In the current study, we investigated the levels of circRNAs in granulosa cells (GCs) derived from human follicular fluid, explored their correlation with female ovarian reserve function and clinical outcomes of assisted reproduction technique (ART), and investigated their effects on the biological functions of GC cell lines (COV434) in vitro. We identified that the levels of circDDX10 in GCs decreased gradually with aging (P < 0.01) and was positively correlated with AMH (r = 0.45, P < 0.01) and AFC (r = 0.32, P < 0.01), but not with FSH and estradiol (P > 0.05). Additionally, circDDX10 was related to the number of oocytes obtained, and good quality embryo rates. Silencing circDDX10 in GCs could markedly up-regulate the expression of apoptosis-related factors, reduce cell proliferation activity, inhibit the expression of steroid hormone synthesis-related factors, and prohibit the synthesis of estradiol. On the contrary, over-expression of circDDX10 had the opposite effect. circDDX10 is expected to become a novel biomarker for predicting the outcomes of ART, and may participate in the regulation of ovarian function by affecting the proliferation and apoptosis of GCs and steroid hormone synthesis.

Comparative efficacy and safety of drug treatment for premature ejaculation: A systemic review and Bayesian network meta-analysis.

To assess the comparative efficacy and safety of drug treatments for premature ejaculation. A systemic review and Bayesian network meta-analysis were executed on randomised controlled trials of drug interventions for premature ejaculation. Intravaginal ejaculation latency time and related adverse effects were outcome measures. A total of 44 RCTs with 11,008 patients were included in our NMA. In therapy <8 weeks, the ranking of drug efficacy was topical creams >selective serotonin reuptake inhibitor (SSRI)+ phosphodiesterase 5 inhibitor (PDE5i) > PDE5i > sertraline > clomipramine > paroxetine > dapoxetine 60 milligram (mg) > dapoxetine 30 mg > fluoxetine>citalopram > duloxetine>placebo. In therapy ≥ 8 weeks, the ranking of drug efficacy was SSRI + PDE5i > topical creams > paroxetine > tramadol > PDE5i > fluoxetine > dapoxetine 60 mg > dapoxetine 30 mg > clomipramine>citalopram > placebo. For total adverse events, clomipramine, dapoxetine 30 mg, dapoxetine 60 mg, paroxetine, PDE5i, SSRI + PDE5i and tramadol had a higher risk than placebo. In conclusion, in ≥8 weeks of therapy, the drug combination of SSRI + PDE5i was the most effective PE therapy. In <8 weeks of therapy, the efficacy of local anaesthetics was best. All drug treatments were ranked better than placebo. In general, drugs with better effects had more obvious side effects.

Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxidative damage to mouse ovarian reserve.

Chemotherapy induces ovarian failure in female children and young female cancer survivors. It has been shown that doxorubicin (DOX), an antitumor drug of the anthracycline group, causes gonadotoxicity via the stimulation of oxidative stress. The inhibition of glycogen synthase kinase-3 (GSK-3) was reported to be able to regulate oxidative stress. The present study assessed whether GSK-3 inhibition confers protection to the ovary against DOX-induced oxidative stress damage. An intraperitoneal injection of DOX was used to induce oxidative damage in the mouse ovary, while the inhibition of GSK-3 was achieved by the administration of SB216763, a small and potent GSK-3 inhibitor. DOX increased the mRNA expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the antioxidant genes heme-oxygenase-1 (HO-1) and catalase (CAT), while reducing the levels of glutathione peroxidase (GSH-Px) and superoxide dismutase-1 (SOD-1) compared with those of the control. When the GSK-3 inhibitor was combined with DOX increased more expression levels of Nrf2 mRNA and restored levels of GSH-Px and SOD-1 mRNA similar to those in the control group. DOX remarkably decreased the Nrf2 protein expression compared to that in the control, which was significantly associated with increased MDA levels. Interestingly, the SB216763 and DOX coadministration restored the Nrf2 protein expression and MDA levels to levels that were similar to those in the control. DOX significantly decreased the number of primordial, primary, preantral and antral follicles while increasing the number of atretic follicles compared to those in the control. SB216763 caused the drastic recovery of these follicles from the DOX effects. SB216763 and DOX coadministration significantly reduced the apoptotic index compared with that with DOX treatment. DOX decreased the serum AMH and E2 levels and increased the FSH levels compared to those in the controls. However, SB216763 and DOX coadministration restored AMH and E2 while decreasing the FSH levels compared to those in the DOX-treated group. In addition, SB216763 and DOX coadministration reduced the mature oocyte abnormalities that resulted from DOX-induced ovarian damage. Given these results, we suggest that GSK-3/Nrf2 is a promising protective pathway against doxorubicin-induced oxidative damage to the ovaries of females at reproductive ages. Thus, GSK-3 could be an attractive target for the research and development of new drugs for preserving ovarian function during chemotherapy.

[Effect of saw palmetto extract on the reproductive function of male rats with chronic prostatitis].

OBJECTIVE: To investigate the effect of saw palmetto extract (SPE) on the reproductive function of rats with chronic prostatitis (CP). METHODS: Forty male SD rats were equally randomized into groups A (blank control), B (blank control + SPE, C (CP model control) and D (CP model + SPE), and the CP model was made by injection of 1% λ-carrageenan solution into the prostate. The animals in groups A and C were gavaged with normal saline while those in groups B and D with SPE at 0.10 g/kg/d, all for 30 successive days. After drug withdrawal, the rats were mated with female ones in the ratio of 1∶1) and sacrificed 7 days later, their bilateral epididymides collected for detection of sperm count and motility. The numbers of pregnancies and fetuses were recorded and compared among different groups. RESULTS: Compared with the rats in group A, those in group C showed a marked decrease in epididymal sperm motility (ï¼»68.01 ± 1.80ï¼½% vs ï¼»62.59 ± 4.82ï¼½%, P < 0.05), but those in groups B and D exhibited no statistically significant difference (ï¼»67.69 ± 4.06ï¼½% and ï¼»67.93 ± 3.39ï¼½%, P > 0.05). There were no statistically significant differences in the count of epididymal sperm, rate of pregnancy and number of fetuses between group A and the other groups (P > 0.05). CONCLUSIONS: SPE can improve the semen parameters of CP rats, and has no adverse effect on the rate of pregnancy and number of fetuses.

[Efficacy and safety of low-intensity extracorporeal shock wave therapy in the treatment of ED: A meta-analysis of randomized controlled trials].

OBJECTIVE: To evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of ED based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to June 2018 for published randomized controlled trials on the treatment of ED by LI-ESWT. We performed literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria, and conducted a meta-analysis of the data obtained using the RevMan 5.3 software. RESULTS: A total of 595 ED cases in 8 double-blind randomized controlled trials (RCT) were included in this study, 362 in the LI-ESWT and 233 in the control group. Compared with the controls, the patients treated by LI-ESWT showed significantly improved IIEF (WMD = 1.70, 95% CI: 0.44－2.96, P = 0.008) and erection hardness score (EHS) (RR = 11.72, 95% CI: 5.13－26.80, P < 0.01). The IIEF scores of the patients were markedly increased at 4 and 24 weeks after LI-ESWT (WMD = 1.43, 95% CI: 0.10－2.75, P = 0.03; WMD = 3.09, 95% CI: 1.49－4.68, P = 0.0002), as well as after the 10th to 12th treatment (WMD = 1.81, 95% CI: 0.31－3.31, P = 0.02) though not after the 5th to 6th (WMD = 1.88, 95% CI: －2.10 to 5.86, P = 0.35). LI-ESWT also significantly increased the IIEF scores in the patients with the baseline IIEF ≥12 (WMD = 2.13, 95% CI: 0.51－3.75, P = 0.01) but not in those with the baseline IIEF ≤11 (WMD = 1.04, 95% CI: －0.96 to 3.03, P = 0.31). No significant adverse events were reported in the 8 RCTs. CONCLUSIONS: As a non-invasive treatment, LI-ESWT is safe and effective and can significantly improve IIEF and EHS in ED patients.

Circular RNA involvement in aging: An emerging player with great potential.

Circular RNA (circRNA) is a class of newly discovered noncoding RNA (ncRNA), presenting as a special covalent loop without a 5' cap or 3' tail. Multiple biological properties of circRNA have been revealed during the past decades, such as widespread expression, high conservation, cell-specificity, tissue-specificity and developmental stage-specific expression patterns, as well as resistance to RNase R digestion. CircRNA also exhibits diverse biological functions, including regulation of host genes, alternative splicing, miRNA sponges, protein traps and even protein synthesis. Recently, a global accumulation of circRNAs during aging has been identified across different species, indicating a potential role as a causal factor in aging and age-related disease. The high stability could be one of the mechanisms contributing to this phenomenon. CircRNA could play a role in aging, such as neural aging, muscle aging, reproductive aging, skin aging, immunosenescence, visual aging and age-related diseases like Alzheimer's disease, via interaction with miRNAs, RNA binding proteins, modulation of parental gene transcription, mainly at the transcriptional and posttranscriptional levels. The present study will focus on the advancement of circRNA regarding aging and age-related diseases. We will also discuss the biogenesis, properties, biological functions, and the perspectives of circRNA.

CFTR variants and renal abnormalities in males with congenital unilateral absence of the vas deferens (CUAVD): a systematic review and meta-analysis of observational studies.

PURPOSE: CFTR variant is the main genetic contributor to congenital (unilateral/bilateral) absence of the vas deferens (CAVD/CUAVD/CBAVD). We performed a systematic review to elucidate the genetic link between CFTR variants, CUAVD, and the associated risk of renal abnormality (RA). METHODS: We searched relevant databases for eligible articles reporting CFTR variants in CUAVD. The frequency of CFTR variants and RA, and the odds ratios (ORs) for common alleles and RA risk, were pooled under random-/fixed-effect models. Subgroup analyses and heterogeneity tests were performed. RESULTS: Twenty-three studies were included. Among CUAVD patients, 46% had at least one CFTR variant, with 27% having one and 5% having two. The allele frequency in CUAVD was 4% for F508del and 9% for 5T. The summary OR for 5T risk in CUAVD was 5.79 compared with normal controls and 2.82 compared with non-CAVD infertile males. The overall incidence of RA was 22% in CUAVD. The pooled OR for RA risk among CUAVD patients was 4.85 compared with CBAVD patients. CONCLUSION: CFTR variants are common in CUAVD, and the 5T allele may be associated with increased CUAVD risk. CUAVD patients bear a higher RA risk than CBAVD patients, but this is not associated with CFTR variants.

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes.

BACKGROUND: The objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos. METHODS: An electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: 'oocyte', 'embryo', 'blastocyst', 'vitrification', 'cryopreservation', 'device', 'survival rate', 'pregnancy rate', etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results. RESULTS: Twelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR = 0.91, 95% CI: 0.80-1.03, P = 0.14; n = 2048) or clinical pregnancy rate (RR = 1.29, 95% CI: 0.80-2.06, P = 0.30; n = 150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive ßHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P > 0.05). The results of the retrospective studies were similar as the prospective studies. CONCLUSIONS: It is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

The Effect of Xialiqi Capsule on Testosterone-Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is common among elderly men, of which inflammation, oxidative stress, proliferative, and apoptotic changes play important roles. Xialiqi (XLQ) capsule, a traditional Chinese herbal formula, is used as a potential drug in treating BPH. This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: sham control, BPH model, high and low dose of XLQ, and finasteride as a positive control group. All groups were treated with appropriate drugs/normal saline for 28 consecutive days. Prostate weights were recorded; histopathological changes and content of IL-8, TNF-α, DHT, SOD, MDA, caspase-3, and PCNA of the prostate were determined. Animals with BPH demonstrated significantly increased prostate weights and prostate index, higher levels of IL-8, TNF-α, DHT, MDA, and PCNA, but lower activity of SOD and reduced expression of caspase-3. After treatment with XLQ, significant reductions of prostate weights, prostate index, IL-8, TNF-α, DHT, MDA, and PCNA, increased activity of SOD, and higher level of caspase-3 were shown. The present study indicates that XLQ can effectively prevent the development of TP-induced BPH model through mechanisms of anti-inflammation, antioxidation, antiproliferation, and proapoptosis.

Low expression of MFN2 is associated with early unexplained miscarriage by regulating autophagy of trophoblast cells.

INTRODUCTION: Miscarriage is a common complication during pregnancy. Mitofusin-2 (MFN2) deficiency in trophoblastic cells is reported to be an important cause for early miscarriage. MFN2 can regulate mitochondrial autophagy, although the mechanisms remain unknown. This study aims to investigate the roles of MFN2 and autophagy in early unexplained miscarriage. METHODS: Immunohistochemistry and western blotting were used to detect the MFN2 expression in villous tissues from women who had early unexplained miscarriage. Western blotting was used to detect the expression of autophagy-related proteins (ATG5, BECLIN1, and LC3), MMP-2, MMP-9, and integrin ß1. Immunofluorescence was used to detect the expression of autophagosome after transfection with GFP-LC3. We used JC-1 to measure the mitochondrial membrane potential and transmission electron microscopy (TEM) to observe the ultrastructure of mitochondria. The levels of ß-hCG and progesterone in the trophoblast were determined by the chemiluminescence method. RESULTS: Immunofluorescence analysis demonstrated that MFN2 in the villous tissues of women with early unexplained miscarriage was significantly lower than that of women in the normal pregnancy group. Increased levels of LC3, ATG5, and BECLIN1 were observed by western blotting. After transfection with MFN2-siRNA, the level of MFN2 decreased, whereas LC3, ATG5, and BECLIN1 levels increased significantly in the trophoblasts. More autophagosomes and significant impairment of mitochondrial function were observed by TEM. The levels of ß-hCG, progesterone, MMP-2, MMP-9, and integrin ß1 were significantly reduced in the MFN2-siRNA group. CONCLUSION: Low expression of MFN2 leads to mitochondrial dysfunction, increased level of autophagy, and trophoblast cell dysfunction, which could be accounted for early unexplained miscarriage.

[Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue of rats with chronic bacterial prostatitis].

OBJECTIVE: To investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP). METHODS: We randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA. RESULTS: Compared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α (ï¼»19.83 ± 6.1ï¼½ vs ï¼»32.93 ± 6.21ï¼½ ng/g prot, P <0.01), IL-8 (ï¼»8.26 ± 0.52ï¼½ vs ï¼»16.2 ± 2.84ï¼½ ng/g prot, P <0.01) and IL-6 (ï¼»1.55 ± 0.11ï¼½ vs ï¼»2.51 ± 1.06ï¼½ ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control (ï¼»20.54 ± 5.78ï¼½ ng/g prot, P <0.01; ï¼»12.43 ± 4.02ï¼½ ng/g prot, P <0.05), 14 d low-dose FT (ï¼»21.95 ± 6.48ï¼½ ng/g prot, P <0.01; ï¼»11.11 ± 2.86ï¼½ ng/g prot, P <0.01), 7 d low-dose FT (ï¼»23.8 ± 6.93ï¼½ ng/g prot, P <0.05; ï¼»12.43 ± 4.02ï¼½ ng/g prot, P <0.05), 14 d high-dose FT (ï¼»19.97 ± 2.58ï¼½ ng/g prot, P <0.01; ï¼»8.83 ± 1.32ï¼½ ng/g prot, P <0.01), and 7 d high-dose FT (ï¼»21.97 ± 3.38ï¼½ ng/g prot, P <0.01; ï¼»12.68±1.97ï¼½ ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls (ï¼»1.76 ± 0.46ï¼½ vs ï¼»2.51 ± 1.06ï¼½ ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05). CONCLUSIONS: Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.

Identification and characterization of human ovary-derived circular RNAs and their potential roles in ovarian aging.

Circular RNAs (circRNAs) have recently been shown to exert effects on multiple pathological processes by acting as miRNA sponges. However, the roles of circRNAs in ovarian senescence are largely unknown. The objective of this study was to identify the circRNAs involved in ovarian aging and predict their potential biological functions. We first performed RNA-sequencing to generate ovarian circRNA expression profiles from young (n = 3) and aging (n = 3) groups. In total, 48,220 circRNAs were identified, of which 194 circRNAs were significantly up-regulated and 207 circRNAs were down-regulated during aging (fold change > 2, P < 0.05). Bioinformatics analysis demonstrated that the metabolic process, regulated secretory pathway, oxidation-reduction process, steroid hormone biosynthesis, and insulin secretion pathways, which may be associated with ovarian aging, were significantly enriched (P < 0.05). The biological characteristics of ovary-derived circRNA, such as back-splicing, RNase R resistance, stability, and alternative splicing, were further validated. Bioinformatics predicted that most of the circRNAs harboured miRNA binding sites, of which circDDX10-miR-1301-3p/miR-4660-SIRT3 axis may be involved in the regulation of ovarian function. Our study indicates that circRNAs are aberrantly expressed in the aging ovary and may play potential roles in the development of ovarian senescence.

Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation.

BACKGROUND: Infertility in mammalian females has been a challenge in reproductive medicine. The causes of female infertility include anovulation, ovulated oocyte defects, abnormal fertilization, and insufficient luteal support for embryo development, as well as early implantation. Ovulation induction, in vitro fertilization and luteal support regimens have been performed for decades to increase fertility rates. The identification of proteins and biochemical factors involved in female reproduction is essential to further increase female fertility rates. Evidence has shown that prostaglandins (PGs) might be involved in the female reproductive process, mainly ovulation, fertilization, and implantation. However, only a few studies on individual PGs in female reproduction have been done so far. This review aimed to identify the pivotal role of prostaglandin E2 (PGE2), a predominant PG, in female reproduction to improve fertility, specifically ovulation, fertilization, embryo development and early implantation. RESULTS: Prostaglandin E2 (PGE2) was shown to play a relevant role in the ovulatory cascade, including meiotic maturation, cumulus expansion and follicle rupture, through inducing ovulatory genes, such as Areg, Ereg, Has2 and Tnfaip6, as well as increasing intracellular cAMP levels. PGE2 reduces extracellular matrix viscosity and thereby optimizes the conditions for sperm penetration. PGE2 reduces the phagocytic activity of polymorphonuclear neutrophils (PMNs) against sperm. In the presence of PGE2, sperm function and binding capacity to oocytes are enhanced. PGE2 maintains luteal function for embryo development and early implantation. In addition, it induces chemokine expression for trophoblast apposition and adhesion to the decidua for implantation. CONCLUSION: It has been shown that PGE2 positively affects different stages of female fertility. Therefore, PGE2 should be taken into consideration when optimizing reproduction in infertile females. We suggest that in clinical practice, the administration of non-steroidal anti-inflammatory drugs, which are PGE2 synthesis inhibitors, should be reasonable and limited in infertile women. Additionally, assessments of PGE2 protein and receptor expression levels should be taken into consideration.

[Protective effect of astaxanthin against epididymal oxidative damagein rats with ornidazole-induced oligoasthenozoospermia].

OBJECTIVE: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ï¼»400 mg/（kg·d）］), C (high-dose ORN ï¼»800 mg/（kg·d）］), D (low-dose ORN ï¼»400 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), and E (high-dose ORN ï¼»800 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (ï¼»45.3±8.7ï¼½% vs ï¼»66.3±8.9ï¼½%, P<0.05) in the epididymal tail and SOD activity in the epididymis (ï¼»116.7±25.3ï¼½ U/mg prot vs ï¼»146.1±23.8ï¼½ U/mg prot, P<0.05), decreased MDA content(ï¼»1.68±0.45ï¼½ nmol/mg prot vs ï¼»1.19±0.42ï¼½ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (ï¼»89.0±9.5ï¼½ vs ï¼»99.9±4.1ï¼½ %, P<0.05) and sperm motility (ï¼»17.9±3.5ï¼½% vs ï¼»27.3±5.3ï¼½ %, P<0.05) but a decrease in the content of MDA (ï¼»2.03±0.30ï¼½ nmol/mg prot vs ï¼»1.52±0.41ï¼½ nmol/mg prot, P<0.05). CONCLUSIONS: AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.