No abstract

Canine circovirus (canine CV) is an etiological agent associated with diarrhea, hemorrhagic gastroenteritis and vasculitis. Although canine CV has been identified and characterized in southern China in recent years, its epidemiology in other regions of China and its precise molecular characteristics have not been examined. In this study, we examined 141 fecal specimens collected from domestic dogs with or without diarrhea in Heilongjiang province, Northeastern China, during 2014 to 2016. A total of 18 out of 141 samples were found to be positive for canine CV by real-time quantitative PCR. In the diarrhea samples, canine CV was detected in coinfections with canine parvovirus 2. More importantly, two different canine CV strains were detected in one sample. Five canine CV genomes were successfully amplified. Sequence analysis showed that there were two unique amino acid changes in the Rep protein (N39S in the K1 strain, and T71A in the XF16 strain). Phylogenetic analysis indicated that canine CV could be divided into four genotypes, and specific nucleotide mutations could be used for confirming the four genotypes. Moreover, recombination analysis revealed that a total of eight recombination events were found in five genomic sequences. Molecular evolution analysis showed that the canine CV has been under purifying selection. This study provides evidence that at least three genotypes of canine CV are co-circulating in China. Continuous epidemiological surveillance is therefore necessary to understand their importance for the evolution of canine CV.

To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, Pcombined = 2.92 × 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, Pcombined = 2.35 × 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Background The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial. Identifying even small differences between these two devices could be useful to guide clinical practices, to further explore their mechanisms, and to promote a better understanding of the optimal methods for inducing labour. Methods Using the population, intervention, comparison, outcomes and study designs (PICOS) principle, we searched the PubMed, EMBASE, OVID, SCI, CENTRAL, ClinicalTrial.gov, and CDSR databases to identify relevant randomised controlled trials (RCTs) from inception through February 14, 2018. The primary outcome was the caesarean delivery rate, and the secondary outcomes focused on efficacy, efficiency, safety, and patient satisfaction. The relative risks or mean differences, including their 95% confidence intervals, were calculated using fixed-effects or random-effects models. All statistical analyses were completed with RevMan version 5.3. Results From a total of 1326 articles, 7 RCTs involving 1159 women were included. There were no significant differences in primary outcomes (RR, 0.88 [0.65, 1.2]; p-value, 0.43) or secondary outcomes identified between single- and double-balloon catheters. However, heterogeneity existed for some aspects. Conclusion Both kinds of balloon catheter have similar levels of efficacy, efficiency, safety and patient satisfaction; however, the single-balloon method is considered to be more cost-effective.

Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate–induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline–deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)–mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.

URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

These results indicate that there may be association between BDNF Val66Met polymorphism and both baseline HRQOL (SF) scores and improvement in HRQOL (SF, MCS) scores in Chinese major depressive patients treated with fluoxetine.