The ecology of the sewer systems: Microbial composition, function, assembly, and network in different spatial locations.

Microbial induced concrete corrosion (MICC) is the primary deterioration affecting global sewers. Disentangling ecological mechanisms in the sewer system is meaningful for implementing policies to protect sewer pipes using trenchless technology. It is necessary to understand microbial compositions, interaction networks, functions, alongside assembly processes in sewer microbial communities. In this study, sewer wastewater samples and microbial samples from the upper part (UP), middle part (MP) and bottom part (BP) of different pipes were collected for 16S rRNA gene amplicon analysis. It was found that BP harbored distinct microbial communities and the largest proportion of unique species (1141) compared to UP and MP. The community in BP tended to be more clustered. Furthermore, significant differences in microbial functions existed in different spatial locations, including the carbon cycle, nitrogen cycle and sulfur cycle. Active microbial sulfur cycling indicated the corrosion risk of MICC. Among the environmental factors, the oxidation‒reduction potential drove changes in BP, while sulfate managed changes in UP and BP. Stochasticity dominated community assembly in the sewer system. Additionally, the sewer microbial community exhibited numerous positive links. BP possessed a more complex, modular network with higher modularity. These deep insights into microbial ecology in the sewer system may guide engineering safety and disaster prevention in sewer infrastructure.

Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes.

Rare coding variants have been proven to be one of the significant factors contributing to spermatogenic failure in patients with non-obstructive azoospermia (NOA) and severe oligospermia (SO). To delineate the molecular characteristics of idiopathic NOA and SO, we performed whole-exome sequencing of 314 unrelated patients of Chinese Han origin and verified our findings by comparing to 400 fertile controls. We detected six pathogenic/likely pathogenic variants and four variants of unknown significance, in genes known to cause NOA/SO, and 9 of which had not been earlier reported. Additionally, we identified 20 novel NOA candidate genes affecting 25 patients. Among them, five (BRDT, CHD5, MCM9, MLH3 and ZFX) were considered as strong candidates based on the evidence obtained from murine functional studies and human single-cell (sc)RNA-sequencing data. These genetic findings provide insight into the aetiology of human NOA/SO and pave the way for further functional analysis and molecular diagnosis of male infertility.

Extracellular vesicles derived from human Sertoli cells: characterizations, proteomic analysis, and miRNA profiling.

BACKGROUND: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. METHODS: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. RESULTS: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. CONCLUSIONS: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility.

Sustainable and effective degradation of aniline by sodium percarbonate activated with UV in aqueous solution: Kinetics, mechanism and identification of reactive species.

In recent decades, sodium percarbonate (SPC) has been widely applied as a solid replacement for H2O2 in advanced oxidation process (AOPs). In this study, ultraviolet (UV) light was utilized for SPC activation to investigate the aniline degradation performance. The effects of SPC dosages and UV irradiation on aniline degradation were elaborated. The removal efficiency was significantly improved by increasing either the SPC dosage or UV irradiation intensity. Moreover, scavenging experiments showed that •OH, CO3•-, and O2•- were the predominant reactive species for aniline degradation. Meanwhile, the variation in the amount of •OH in the UV/SPC system was monitored, which revealed the dominant role of •OH. As a result, the mechanism of aniline degradation by the UV/SPC system was demonstrated based on confirmed free radicals. Furthermore, aniline degradation by the UV/H2O2 and UV/H2O2/Na2CO3 system were compared with the UV/SPC system, and an enhancement by the addition of Fe(II) in the UV/SPC system was verified. Aniline degradation was not significantly affected by the initial pH or the presence of Cl-, SO42- while NO3-, HCO3- and humid acid (HA) suppressed the reaction. In general, the UV/SPC system is a novel, green, and promising technology for aniline removal from aqueous solutions.

[Influence of epididymitis history on the results of vasoepididyostomy in patients with epididymal obstruction].

OBJECTIVE: To evaluate the influence of epididymitis history on the results of microsurgical vasoepididymostomy and spontaneous pregnancy in patients with epididymal obstruction. METHODS: Totally 205 patients with epididymal obstruction underwent microsurgical two-suture longitudinal intussusception vasoepididymostomy from January 2014 to December 2016. After surgery, we evaluated the semen quality of the patients every 3 months till conception and compared the rates of patency and spontaneous pregnancy between the patients with and those without an epididymitis history. RESULTS: The patients ranged in age from 22 to 46 (mean 31) years, 37 (22.2%) with and 126 (77.8%) without an epididymitis history among the 163 patients for whom a 25.4-month follow-up (from 7 to 42 months) was completed. No statistically significant differences were observed postoperatively between the patients with and those without an epididymitis history in the patency rate (73.0% vs 81.7%, P = 0.243), sperm concentration (18 ï¼»1.3－33.6ï¼½ vs 15.2 ï¼»0.8－33.4ï¼½ ×106/ml, P = 0.710), percentage of progressively motile sperm (27.5 ï¼»0－46.1ï¼½% vs 19.3 ï¼»0－41ï¼½% (P = 0.592) or rate of spontaneous pregnancy (24.3% vs 38.9%, P = 0.104). CONCLUSION: Microsurgical vasoepididymostomy is an effective method for the treatment of epididymal obstruction, and epididymitis history does not affect the results of the strategy.

[Application value of color Doppler ultrasonography in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis].

OBJECTIVE: To assess the accuracy and value of ultrasonography in the diagnosis of ruptured tunica albuginea (RTA) of the corpus cavernosum penis. Factors affecting prognosis were analyzed. METHODS: This retrospective study included 57 cases of RTA of the corpus cavernosum penis ultrasonographically diagnosed and surgically treated in Peking University First Hospital from 2013 to 2021. We analyzed the location, size and number of ruptures and the presence or absence of urethral injury, and compared the intraoperative with the ultrasonographic findings. RESULTS: Of the 57 cases of RTA of the corpus cavernosum penis diagnosed by ultrasonography, 54 (94.7%) were confirmed by surgery. Preoperative ultrasonography indicated 2 cases of bilateral RTA and 6 cases of urethral injury, while surgery revealed 7 cases of bilateral RTA and 13 cases of combined urethral injury. Those with urethral injury developed no urethral stricture or urinary fistula after one-stage urethral repair. And no severe or moderate ED was found in any of the patients during the 12-month follow-up. CONCLUSION: Ultrasonography has a high accuracy in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis, and contributes to the determination of the site of surgical incision.

Rs884225 polymorphism is associated with primary hypertension by compromising interaction between epithelial growth factor receptor (EGFR) and miR-214.

Genetic variations in the 3'UTR of mRNAs as well as sequences of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) can affect gene expression by interfering with the binding between them. In this study, we investigated the role of the following polymorphisms in the risk of hypertension: the 774T > C (rs17337023) polymorphism located in the EGFR 3' untranslated region (3'UTR), the rs884225 polymorphism located in the sequence of miR-214, and the single nucleotide polymorphisms (SNPs) rs325797437, rs344501106, rs81286029 and rs318656749 located in the promoter of lncRNA MEG3. Taqman genotyping assays and haplotype analysis tools were used to measure the MEG3 haplotypes and the rs17337023 and rs884225 polymorphisms genotypes. The relationship between MEG3, miR-214 and EGFR was validated using computational analysis and luciferase assays. Unlike other polymorphisms, only patients grouped according to their rs884225 genotypes exhibited varied EGFR mRNA and protein levels, which indicated that the rs884225 genotype is associated with the expression of EGFR mRNA and protein levels. MiR-214 was confirmed to bind to MEG3 and 3'UTR of EGFR by showing that the transfection of exogenous miR-214 significantly down-regulated the luciferase activity of A549 and H460 cells transfected with wild-type MEG3 or wild-type EGFR 3' UTR. Additionally, MEG3 overexpression inhibited miR-214 expression while elevating the EGFR mRNA and protein expressions. Meanwhile, MEG3 down-regulation demonstrated an opposite result, thus establishing the MEG3/miR-214/EGRF signalling pathway. Our study confirmed that the T > C substitution of rs884225 polymorphism located in miR-214 binding site in the 3'UTR of EGFR is associated with increased risk of primary hypertension.

Effects of genetic variations in Acads gene on the risk of chronic obstructive pulmonary disease.

Short-chain acyl-CoA dehydrogenase (SCAD), encoded by the Acads gene, functions in the mitochondrial ß-oxidation of saturated short-chain fatty acids. SCAD deficiency results in mitochondrial dysfunction, which is one underlying biological mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis. In this case-control study, we aimed to examine the effects of Acads gene polymorphisms on the susceptibility to COPD. A total of 16 tagging single-nucleotide polymorphisms (SNPs) in Acads gene region was identified and genotyped in 646 unrelated ethnic Chinese Han individuals including 279 patients with COPD and 367 healthy controls, their allelic and genotypic associations with COPD were determined by different genetic models. Furthermore, we estimated the linkage disequilibrium and haplotypes from these tested variants and determined the effects of haplotypes on the risk of COPD. The allelic and genotypic frequencies of SNPs rs2239686 and rs487915 in Acads gene were significantly different between COPD patients and controls, no statistically significant results were observed for other SNPs. Minor alleles A of rs2239686 and T of rs487915 were associated with a decreased pulmonary function and an increased COPD risk in a dominant manner. Functional analysis indicated that the risk allele A of rs2239686 could increase Acads expressions and the intracellular reactive oxygen species content. Haplotype analysis revealed that the haplotypes CTCCT in block 2 (rs3794216-rs3794215-rs34491494-rs558314-rs7312316) as well as GC in block 3 (rs2239686-rs487915) were protective against COPD, while haplotypes CTCGC in block 2 and AT in block 3 exhibited significant associations with the increased susceptibility to COPD. Our results suggest that Acads gene could potentially be a risk factor of COPD and thus its genetic variants might be as genetic biomarkers to predict the COPD susceptibility.

Genome-wide analysis of circular RNAs involved in Marek's disease tumourigenesis in chickens.

Marek's disease (MD), induced by Marek's disease virus (MDV), is a lymphotropic neoplastic disease and causes huge economic losses to the poultry industry. Non-coding RNAs (ncRNAs) play important regulatory roles in disease pathogenesis. To investigate host circular RNA (circRNA) and microRNA (miRNA) expression profile, RNA sequencing was performed in tumourous spleens (TS), spleens from the survivors (SS) without any lesion after MDV infection, and non-infected chicken spleens (NS). A total of 2,169 circRNAs were identified and more than 80% of circRNAs were derived from exon. The flanking introns of 1,744 exonic circRNAs possessed 579 reverse complementary matches (RCMs), which mainly overlapped with chicken repeat 1 family (CR1F). It suggested that CR1F mediated the cyclization of exons by intron pairing. Out of 2,169 circRNAs, 113 were differentially expressed circRNAs (DECs). The Q-PCR and Rnase R digestion experiments showed circRNA possessed high stability compared with their linear RNAs. Integrated with previous transcriptome data, we profiled regulatory networks of circRNA/long non-coding RNA (lncRNA)-miRNA-mRNA. Extensive competing endogenous RNA (ceRNA) networks were predicted to be involved in MD tumourigenesis. Interestingly, circZMYM3, an intronic circRNA, interacted with seven miRNAs which targeted some immune genes, such as SWAP70 and CCL4. Gga-miR-155 not only interacted with circGTDC1 and circMYO1B, but also targeted immune-related genes, such as GATA4, which indicated the roles of non-coding RNAs played to mediate immune responsive genes. Collectively, this is the first study that integrated RNA expression profiles in MD model. Our results provided comprehensive interactions of ncRNAs and mRNA in MD tumourigenesis.

Efficacy of dapoxetine treatment in Chinese patients with premature ejaculation and possible factors affecting efficacy in the real-world practice.

BACKGROUND: The treatment effect of dapoxetine in real-world practice is not well established. This study was to investigate the factors influencing efficacy of dapoxetine for the treatment of Premature ejaculation (PE) in the real-world setting. METHODS: Altogether 154 patients were followed up between Jan 2015 and Dec 2015. The clinical global impression of change (CGIC), premature ejaculation profile (PEP), the estimated intravaginal ejaculation latency time (eIELT) and estimated number of intravaginal thrusts before ejaculation (NITBE) were collected. The clinical characteristics of patients with CGIC = 0 and CGIC≥1 were compared. RESULTS: After 4 weeks treatment, an obvious improvement compared with the baseline was found regarding mean eIELT (2.4 ± 1.6 min vs 1.0 ± 0.7 min, P < 0.001) and mean NITBE (85.9 ± 61.9 times vs 37.4 ± 28.6 times, P < 0.001). The proportion of patients with a self-evaluation of at least "slightly better" and were categorized into "CGIC≥1" group was 70.1%. There were significant differences between patients in the "CGIC = 0" and "CGIC≥1" groups regarding mean NITBE (P = 0.010) and PEDT (P = 0.009) score at baseline. The adverse effects were acceptable. CONCLUSION: Dapoxetine was well-tolerated and improved the sexual satisfaction of patients with PE. The severity of PE based on PEDT and NITBE suggest that there could be an effectiveness change with dapoxetine use in real-world practice.

[Point electro-cauterization versus holmium laser cauterization in the treatment of post-ejaculation hematuria].

OBJECTIVE: To investigate the advantages and disadvantages of point electro-cauterization (PEC) and holmium laser cauterization (HLC) in the treatment of post-ejaculation hematuria. METHODS: From January 2015 to December 2018, 73 patients with post-ejaculation hematuria, aged 24－63 (36.8 ± 4.2) years, underwent PEC (n = 35) or HLC (n = 38) after failure to respond to 3 months of conservative treatment. We compared the hospital days, total hospitalization expenses, maximum urinary flow rate (Qmax), average urinary flow rate (Qavg), Hamilton Anxiety Rating Scale (HAMA) score, postoperative duration of hematuria, and recurrence rate at 3 and 6 months after surgery. RESULTS: All the patients experienced first ejaculation but no post-ejaculation hematuria at 1 month after operation. The recurrence rates were lower in the PEC than in the HLC group at 3 months (5.71% vs 2.63%, P > 0.05) and 6 months postoperatively (8.57% vs 5.26%, P > 0.05). Compared with the baseline, the Qmax was decreased from (18.56 ± 2.53) ml/s to (13.68 ± 3.31) ml/s (P < 0.05) and the Qavg from (14.35 ± 2.26) ml/s to (9.69±1.84) ml/s in the PEC group at 1 month after surgery (P < 0.01), but neither showed any statistically significant difference in the HLC group. Mild to moderate anxiety was prevalent in the patients preoperatively, particularly in those without job or regular income and those with a long disease course or frequent onset, the severity of which was not correlated with age, education or marital status. The HAMA score was decreased from18.65 ± 4.33 before to 12.35 ± 3.63 after surgery in the PEC group (P < 0.01), and from 16.88 ± 2.11 to 6.87 ± 4.36 in the HLC group (P < 0.01). The mean hospital stay was significantly longer in the former than in the latter group (ï¼»5.2 + 1.3ï¼½ vs ï¼»3.4 ± 0.5ï¼½ d, P < 0.01), while the total cost markedly lower (ï¼»6.35 ± 1.20ï¼½ vs ï¼»12.72 ± 2.15ï¼½ thousand RMB ¥, P < 0.05). CONCLUSIONS: Both PEC and HLC are safe and effective for the treatment of post-ejaculation hematuria, with no significant difference in the recurrence rate at 3 and 6 months after operation, but their long-term effect needs further follow-up studies. PEC may increase the risk of negative outcomes of the postoperative urinary flow rate, while HLC has the advantages of better relieving the patient's anxiety, sooner discharge from hospital and earlier recovery from postoperative hematuria, though with a higher total cost than the former.

Comparative transcriptome analyses of genes involved in sulforaphane metabolism at different treatment in Chinese kale using full-length transcriptome sequencing.

BACKGROUND: Sulforaphane is a natural isothiocyanate available from cruciferous vegetables with multiple characteristics including antioxidant, antitumor and anti-inflammatory effect. Single-molecule real-time (SMRT) sequencing has been used for long-read de novo assembly of plant genome. Here, we investigated the molecular mechanism related to glucosinolates biosynthesis in Chinese kale using combined NGS and SMRT sequencing. RESULTS: SMRT sequencing produced 185,134 unigenes, higher than 129,325 in next-generation sequencing (NGS). NaCl (75 mM), methyl jasmonate (MeJA, 40 µM), selenate (Se, sodium selenite 100 µM), and brassinolide (BR, 1.5 µM) treatment induced 6893, 13,287, 13,659 and 11,041 differentially expressed genes (DEGs) in Chinese kale seedlings comparing with control. These genes were associated with pathways of glucosinolates biosynthesis, including phenylalanine, tyrosine and tryptophan biosynthesis, cysteine and methionine metabolism, and glucosinolate biosynthesis. We found NaCl decreased sulforaphane and glucosinolates (indolic and aliphatic) contents and downregulated expression of cytochrome P45083b1 (CYP83b1), S-alkyl-thiohydroximatelyase or carbon-sulfur lyase (SUR1) and UDP-glycosyltransferase 74B1 (UGT74b1). MeJA increased sulforaphane and glucosinolates contents and upregulated the expression of CYP83b1, SUR1 and UGT74b1; Se increased sulforaphane; BR increased expression of CYP83b1, SUR1 and UGT74b1, and increased glucosinolates contents. The desulfoglucosinolate sulfotransferases ST5a_b_c were decreased by all treatments. CONCLUSIONS: We confirmed that NaCl inhibited the biosynthesis of both indolic and aliphatic glucosinolates, while MeJA and BR increased them. MeJA and BR treatments, conferred the biosynthesis of glucosinolates, and Se and MeJA contributed to sulforaphane in Chinese kale via regulating the expression of CYP83b1, SUR1 and UGT74b1.

Pregnancy and live birth rates after microsurgical vasoepididymostomy for azoospermic patients with epididymal obstruction.

STUDY QUESTION: Can microsurgical vasoepididymostomy (MVE) be an effective treatment for azoospermic men with epididymal obstruction? SUMMARY ANSWER: MVE is an effective treatment for epididymal obstruction, with overall patency and live birth rates of 76.3% and 34.8%, respectively. WHAT IS KNOWN ALREADY: We showed that MVE was an effective treatment for non-vasectomized patients with epididymal obstruction and prior failed sperm retrieval for ICSI. ICSI is the preferred treatment for obstructive azoospermia in some reproductive centers. Some small studies documented that MVE could achieve high patency and pregnancy rates. STUDY DESIGN, SIZE, DURATION: This retrospective study was designed to investigate the natural pregnancy and live birth rates after MVE and to identify possible predictors of pregnancy. From January 2011 to July 2013, 241 patients underwent MVE for epididymal obstruction in our andrology center. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent scrotal exploration and MVE. Semen was analyzed every 3 months postoperatively until pregnancy was achieved. Patency, pregnancy and live birth rates were evaluated. Preoperative and intraoperative data were compared between patent and non-patent groups to identify factors affecting the patency rate. Predictors of pregnancy were identified by univariate and multivariate analyses with Cox regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 198 males (82.2%) were analyzed. The mean (±SD) age of males and female partners was 31.0 ± 5.8 and 28.4 ± 4.4 years, respectively. Sperm was present in the ejaculate of 151 patients (76.3%) postoperatively. Patency rates were increased for patients with bilateral anastomosis, distant anastomosis and motile sperm in epididymal fluid. Overall, 81/198 males (40.9%) reported pregnancy in partners and 73 newborns were delivered. The overall live birth rate was 34.8%. Male age (hazard ratio (HR) [95% CI] 0.407 [0.203-0.816], P = 0.011), sperm concentration (HR [95% CI] 4.988 [2.777-8.957], P < 0.001) and forward motility (HR [95% CI] 1.751 [1.042-2.945], P = 0.035) were predictors of pregnancy. LIMITATIONS, REASONS FOR CAUTION: A randomized control trial comparing pregnancy rates, live birth rates, risks and medical costs of MVE and IVF/ICSI is needed. The sample size of females >35 years old was small, so we could not determine whether female age was a predictor of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: MVE is an effective therapy for azoospermic patients with epididymal obstruction. Sperm concentration and forward motility may predict pregnancy after the procedure. Microsurgical reconstruction could be a first choice for epididymal obstruction. STUDY FUNDING/COMPETING INTERESTS: No external funding was received. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Virtual screening in small molecule discovery for epigenetic targets.

Epigenetic modifications are critical mechanisms that regulate many biological processes and establish normal cellular phenotypes. Aberrant epigenetic modifications are frequently linked to the development and maintenance of several diseases including cancer, inflammation and metabolic diseases and so on. The key proteins that mediate epigenetic modifications have been thus recognized as potential therapeutic targets for these diseases. Consequently, discovery of small molecule inhibitors for epigenetic targets has received considerable attention in recent years. Here, virtual screening methods and their applications in the discovery of epigenetic target inhibitors are the focus of this review. Newly emerging approaches or strategies including rescoring methods, docking pose filtering methods, machine learning methods and 3D molecular similarity methods were also underlined. They are expected to be employed for identifying novel inhibitors targeting epigenetic regulation more efficiently.

Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population.

AIM: Adiponectin has been implicated in the development of chronic obstructive pulmonary disease (COPD). The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. METHODS: Ten single-nucleotide polymorphisms (SNP) in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models. RESULTS: Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, P=0.022). The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC (P<0.05). Haplotypes GC in block 1 (rs4783244-rs12922394) as well as GTAC and ATGT in block 3 (rs4783266-rs11640522-rs11646849-rs11860282) significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 (rs11646011- rs11640875) and ATGC in block 3 were protective against COPD. CONCLUSION: CDH13 genetic variants determine Chinese individuals' susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD.

Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

Clinical investigation of a novel surgical device for circumcision.

PURPOSE: We investigated the performance of a novel device for adult circumcision, that is the circular cutter with stapled anastomosis for circumcision. MATERIALS AND METHODS: A total of 62 men with a mean ± SD age of 28 ± 8 years were enrolled from June to September 2012 to undergo circumcision using the circular cutter with stapled anastomosis. The device used 18 staples for anastomosis, which fall out during the recovery course, as designed. Patients were followed at day 3, and weeks 1, 2, 4 and 12 after the procedure. Outcome measures were evaluated, including patient safety, procedural time, patient satisfaction and complication rate. RESULTS: Average procedural time needed to use the device was 7.7 ± 2.6 minutes. Patients returned to full physical activity on postoperative day 3. The overall complication rate was 4.8%, including 1 case of intraoperative bleeding due to operator inexperience and 2 of a delay in staples falling out. No patient experienced wound infection or excessive foreskin excision. No incision site edema was observed beyond postoperative day 7. All enrolled patients were satisfied with the postoperative penile cosmesis. CONCLUSIONS: The circular cutter with stapled anastomosis for circumcision is a 1-step device that can achieve excellent postoperative results with minimal procedural time. Therefore, it has the potential to enable the performance of circumcision as a rapid turnover bedside procedure.

Genetic variations in RORα are associated with chronic obstructive pulmonary disease.

Retinoic acid receptor-related orphan receptor-α (RORα) plays a key role in the regulation of lipid and cholesterol metabolism that has been implicated in the development of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine the frequencies of single-nucleotide polymorphisms (SNPs) in RORα gene in a Chinese population and their possible association with COPD susceptibility. Nine tagging SNPs, including rs17270181, rs1898413, rs17270216, rs8033552, rs8036966, rs7169364, rs340002, rs340023 and rs11630262, were screened in 279 COPD patients and 367 controls by the SNaPshot method. Association analysis of genotypes and haplotypes constructed from these loci with COPD was conducted under different genetic models. Alleles or genotypes of rs8033552 distributed significantly differently in COPD patients and controls (allele: P=0.0001, false discovery rate (FDR) Q=0.004, odds ratios (OR): 1.62 and 95% confidence interval (CI): 1.27-2.07; genotype: P=0.0005, FDR Q=0.008). The allele A at rs8033552 was potentially associated with an increased risk of COPD in additive model, displaying ORs of 1.62 (95% CI: 1.17-2.26, P=0.004, FDR Q=0.019) in subjects with genotypes AG vs GG and 2.69 (95% CI: 1.47-4.93, P=0.001, FDR Q=0.011) in subjects with genotypes AA vs GG, respectively. In haplotype analysis, we observed haplotypes GGAGATGTG and GGAGCTGTG had protective effects, whereas haplotypes GGAGATACA and GGAGATACG were significantly associated with the increased risk of COPD. These data suggest that RORα may be a potential risk gene for COPD.

Microsurgical vasoepididymostomy is an effective treatment for azoospermic patients with epididymal obstruction and prior failure to achieve pregnancy by sperm retrieval with intracytoplasmic sperm injection.

STUDY QUESTION: Can microsurgical vasoepididymostomy (MVE) be used to treat azoospermia in men with epididymal obstruction who have had a prior attempt at sperm retrieval with ICSI and failed to achieve a pregnancy? SUMMARY ANSWER: MVE is an effective treatment for epididymal obstruction. WHAT IS KNOWN ALREADY: MVE is an effective treatment for non-vasectomized patients with epididymal obstruction. However, ICSI is the preferred treatment for patients with obstructive azoospermia in some reproductive centers. The clinical pregnancy rate in per ICSI cycle is <40% and more than half of couples need repeated ICSI. Some couples cannot bear the high medical costs or the pain associated with repeated IVF/ICSI. Therefore, MVE may be an alternative treatment for such patients. STUDY DESIGN, SIZE AND DURATION: This retrospective study investigated whether MVE could be used to treat patients with epididymal obstruction and a previous failed ICSI attempt. From January 2009 to July 2012, 268 patients underwent MVE for epididymal obstruction in our center; we included 68 who had experienced failure of at least one cycle of ICSI in this study. MATERIALS, SETTING, METHODS: We studied 68 patients with obstructive azoospermia who were treated by MVE and had previously undergone surgical sperm recovery and ICSI. The patients were divided into two groups according to the sperm retrieval method used in their ICSI attempt: percutaneous epididymal sperm aspiration (PESA) (41.2%, 28/68) and testicular sperm extraction (TESE) (58.8%, 40/68). We evaluated the obstructive causes, patency, pregnancy and live birth rates and the effect of sperm retrieval methods on the outcome of MVE. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 62 patients (91.2%) showed epididymal obstruction, 2 (2.9%) intratesticular obstruction and 4 (5.9%) vasal obstruction. The mean age was 30.4 ± 5.3 years (range 22-48 years). We followed up 53 (85.5%) at a mean follow-up of 19.8 ± 9.1 months (range 6-43 months). The total patency and natural pregnancy rates were 79.2% (n = 42) and 35.8% (n = 19), respectively. The overall live birth rate was 28.3%. The results of MVE did not differ between the two groups: PESA and TESE. LIMITATIONS, REASONS FOR CAUTION: A randomized controlled trial comparing pregnancy rates, live birth rates, risks and medical costs of MVE and IVF/ICSI is needed. The size of our sample was limited, so we did not reveal significantly different patency, pregnancy and live birth rates between PESA and TESE. A larger sample size is needed to evaluate the effect of sperm retrieval on patency, pregnancy and live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: Epididymal obstruction is the most common obstructive cause in non-vasectomized patients. Data from this study have shown that MVE is an effective therapy for such azoospermic patients with epididymal obstruction and prior failed ICSI for pregnancy. Obstructive causes should be differentiated to select optimal therapy for patients with obstructive azoospermia in reproductive centers. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no competing interests to declare.

The self-estimation index of erectile function-no sexual intercourse (SIEF-NS): a multidimensional scale to assess erectile dysfunction in the absence of sexual intercourse.

INTRODUCTION: A new concept of Erectile Dysfunction with No Sexual Intercourse (ED-NS) is proposed to acknowledge the subpopulation of patients who are unable to achieve or sustain an erection in the absence of sexual intercourse. Since the commonly used ED diagnostic tool, International Index of Erectile Function Questionnaire is not able to adequately assess the erectile function (EF) in the absence of intercourse, the researchers developed a new 10-item questionnaire to better evaluate the EF in this special patient subpopulation: Self-Estimation Index of Erectile Function-No Sexual Intercourse (SIEF-NS). AIM: To validate the reliability, sensitivity and specificity of SIEF-NS. METHODS: The study was carried out in three phases. Phase one applied component analysis to 126 ED-NS patients to search for the primary factors and Cronbach's alpha standardized statistic values for SIEF-NS. Phase two applied discriminant analysis to participants' (212 ED-NS patients and 193 normal controls) scores on each question item, each factor and the overall 10-item questionnaire. Phase three investigated SIEF-NS's capability of evaluating treatment effect on 41 ED-NS patients. MAIN OUTCOME MEASURES: Reliability, sensitivity and specificity were defined and used to evaluate the performance of SIEF-NS. RESULTS: EF by autonomic response (factor 1) and EF with potential sexual partners (factor 2) are the two primary factors with eigenvalues greater than 1.0. High degree of internal consistency was observed for the two factors and the 10-item questionnaire (Cronbach's alpha values: 0.871 for 10 items, 0.84 for factor 1, and 0.823 for factor 2). SIEF-NS demonstrated adequate construct validity, high sensitivity (0.925) and specificity (0.829) to diagnose ED-NS. The EF scores of ED-NS patients post treatment showed significant improvement (P < 0.05). CONCLUSION: SIEF-NS can be used to identify ED-NS patients and detect treatment-related EF changes in ED-NS patients.