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Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations. Methods and Results: We genotyped members of a 5-generational Han Chinese family with CADASIL patients and identified an R133C mutation in the NOTCH3 gene. Clinical analysis demonstrated that the penetrance of the mutation was not complete. Five of the mutation carriers, not exposed to the known vascular risk factors, did not show any clinical feature of CADASIL, suggesting the importance of environmental factors to the development of this disease. Conclusions: Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL. [ABSTRACT FROM AUTHOR]

Autophagy plays an important role in the infectious processes of diverse pathogens. For instance, cellular autophagy could be harnessed by viruses to facilitate replication. However, it is still uncertain about the interplay of autophagy and swine acute diarrhea syndrome coronavirus (SADS-CoV) in cells. In this study, we reported that SADS-CoV infection could induce a complete autophagy process both in vitro and in vivo, and an inhibition of autophagy significantly decreased SADS-CoV production, thus suggesting that autophagy facilitated the replication of SADS-CoV. We found that ER stress and its downstream IRE1 pathway were indispensable in the processes of SADS-CoV-induced autophagy. We also demonstrated that IRE1-JNK-Beclin 1 signaling pathway, neither PERK-EIF2S1 nor ATF6 pathways, was essential during SADS-CoV-induced autophagy. Importantly, our work provided the first evidence that expression of SADS-CoV PLP2-TM protein induced autophagy through the IRE1-JNK-Beclin 1 signaling pathway. Furthermore, the interaction of viral PLP2-TMF451-L490 domain and substrate-binding domain of GRP78 was identified to activate the IRE1-JNK-Beclin 1 signaling pathway, and thus resulting in autophagy, and in turn, enhancing SADS-CoV replication. Collectively, these results not only showed that autophagy promoted SADS-CoV replication in cultured cells, but also revealed that the molecular mechanism underlying SADS-CoV-induced autophagy in cells. Author summary: SADS-CoV, a novel bat-origin pathogen belonging to the family Alphacoronavirus, was confirmed to be the aetiological agent that caused mass death of piglets in southern China in 2017. Strikingly, since the outbreak of SADS-CoV, multiple studies have highlighted the risk of cross-species transmission due to its broad cell tropism. A better understanding of the pathogenic mechanisms is expected to result in a more specific SADS-CoV prevention and control measures. As yet, the pathogenic mechanisms of SADS-CoV have so far not been characterized well. Here, we found that SADS-CoV infection induced a complete autophagy process in vitro and in vivo to facilitate virus propagation. Furthermore, it's indicated that ER stress and IRE1 pathway played indispensable functions in SADS-CoV-induced autophagy. Notably, we have provided first evidence that SADS-CoV PLP2-TMF451-L490 domain induced autophagy by interacting with substrate-binding domain of GRP78 to activate the IRE1-JNK-Beclin 1 signaling pathway. Overall, our study presented detailed mechanism of SADS-CoV-induced autophagy as well as a contribution for SADS-CoV pathogenesis. [ABSTRACT FROM AUTHOR]

In an effort to trace the evolution of porcine epidemic diarrhea virus (PEDV), S1 and ORF3 genes of viruses identified in 41 pig farms from seven regions (North, Northeast, Northwest, Central, East, South West, and South, respectively) of China in 2015 were sequenced and analyzed. Sequence analysis revealed that the 41 ORF3 genes and 29 S1 genes identified in our study exhibited nucleotide homologies of 98.2%–100% and 96.6%–100%, respectively; these two genes exhibited low nucleotide sequence similarities with classical CV777 strain and early Chinese strain LZC. Phylogenetic analysis indicated that the identified PEDV strains belonged to global non S-INDEL strains, and exhibited genetic diversity; S1 gene of the HLJ2015/DP1-1 strain harbored an unique deletion of 12 nucleotides (A1130CAACTCCACTG1141); while the Chinese PEDV S-INDEL reference strains included two types of the “CV777” S-INDEL as well as the “US” S-INDEL, and all co-circulated with Chinese non S-INDEL strains. Of 29 identified S1 genes, the SS2 epitope (Y748SNIGVCK755) was highly conserved, while the SS6 epitope (L764QDGQVKI771) and pAPN receptor-binding region (aa 490–615) exhibited amino substitutions. Nine possible recombination events were identified between the 29 identifed S1 genes and the 3 S1 reference genes from early Chinese PEDV strains. The complete S genes of selected Chinese PEDV field strains (2011–2015) showed 5.18%–6.07% nucleotide divergence, which is far higher than the divergence observed in early Chinese PEDV strains (3.1%) (P<0.05). Our data provide evidence that PEDV non S-INDEL strains with genetic diversities and potential recombination circulate in seven regions of China in 2015; Chinese PEDV S-INDEL strains exhibit genetic diversity and co-circulate with non S-INDEL strains. [ABSTRACT FROM AUTHOR]

Objective: The abuse of antimicrobials is a serious concern in China. Several measures have been taken to improve the rational use of antimicrobials, including the establishment of a national surveillance network for antimicrobial use. This study describes the dynamic changes in antimicrobial use in China between 2001 and 2010, with the scope of identifying targets to improve the prescription of antimicrobials. Methods: Five point prevalence surveys were performed in hospitals across mainland China in 2001, 2003, 2005, 2008, and 2010. All inpatients who were admitted for at least 24 hours were included in the study. Details regarding antimicrobial use by these patients and the collection of samples for bacterial culture from inpatients administered therapeutic antimicrobials were recorded. Results: The surveys encompassed tertiary hospitals from all 31 provinces of mainland China. Antimicrobial use prevalence decreased from 54.79% in 2001 to 46.63% in 2010. While this decline was observed in most hospital departments, antimicrobial use remained stable or increased in others. Antimicrobial use prevalence was relatively high in the Pediatrics departments and general intensive care units, whereas it was lower in the Obstetrics (Neonatal group) departments in each survey. The proportion of patients administered a single antimicrobial increased from 60.78% in 2001 to 70.16% in 2010, while the proportion of administration of two or more antimicrobials declined. The bacterial culture rate increased from 25.22% in 2003 to 34.71% in 2010. Antimicrobial use prevalence (47.96% vs 46.16%), bacterial culture rate (36.40% vs 34.19%), and the proportion of administration of a single antimicrobial (71.41% vs 67.33%) were higher in teaching hospitals than in nonteaching hospitals in 2010. Conclusion: Although measures for enhancing the rational use of antimicrobials have been effective, further improvements are required. The findings from this study can promote such improvements. [ABSTRACT FROM AUTHOR]

Background: Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin and is considered key factor for maintaining normal serotonin transmission in the central neuron system (CNS). Gene-disease association studies have reported a relationship between TPH2 and major depressive disorder (MDD) in different populations, however subsequent studies have produced contradictory results. Objectives: We performed a systematic overview and a meta-analysis with all available data up-to-date. Methods: We scrutinized PubMed, Embase, HuGNet and China National Knowledge Infrastructure (CNKI ) and last update was held on October 2011. We also searched the manuscripts and the supplementary documents of the published genomewide association studies in the field. Effect sizes of independent loci that have been studied in more than 3 articles were synthesized using fixed and random effects models. Results: We found 27 eligible articles that studied a total of 74 single nucleotide polymorphisms (SNPs). Finally, 12 independent loci were included in the meta-analysis. The synthesis of the data shown that two SNPs (rs4570625 and rs17110747) were associated with MDD using fixed effects models. SNP rs4570625 had low heterogeneity and remained significant using the more conservative random effects calculations with a summary OR = 0.83 (95% CI: 0.73-0.96). Conclusion: The current study identified a SNP (rs4570625) with strong epidemiological credibility; however more studies are required to provide robust evidence for other weak associations. [ABSTRACT FROM AUTHOR]

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P<0.05), but similar to those of seasonal influenza (P>0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China. [ABSTRACT FROM AUTHOR]