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.

Background: Transcatheter closure is an effective approach for perimembranous ventricular septal defects (PMVSD). However, atrioventricular blocks (AVB) emerged possibly due to the close proximity of the PMVSD to the conduction system, but concern for the complication was not adequately emphasized. In this study, we report the incidence of AVBs, in and after transcatheter closure of a PMVSD, and the outcome of the complication in our center. Methods: One hundred and sixty-eight PMVSD patients were accepted for transcatheter closure with Amplazter PMVSD occluder (AGA Medical, Plymouth, Minn., USA). The procedure was discontinued when a secondor third-degree AVB occurred. A steroid was administered to all patients who developed AVBs. Temporary pacemakers were inserted in patients who developed a complete AVB or Mobitz type II AVB during or after the procedure. Results: During the follow-up period of 6-24 mo (mean 10.6±3.9), the incidence of AVBs occurring during or after transcatheter closure of PMVSD was 3.5%. The AVB disappeared quickly after discontinuing the procedure in patients who developed AVBs during the procedure, whereas the AVBs disappeared between 2 and 21 d (mean 8.0±8.8) in the patients who developed AVBs after the procedure. However, complete right bundle branch block (CRBBB) was observed, and a transient complete AVB emerged after 8 mo in 1 case, incomplete right bundle branch block (IRBBB) in 1 case, and CRBBB and left anterior hemiblock (LAH) in 1 case. Conclusions:The AVB is a serious complication during and after transcathter closure of PMVSD. More attention should be paid to the complication, and multicentres are required to monitor the complication.

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Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.