Identifying Candidate Genes Associated with Sporadic Amyotrophic Lateral Sclerosis via Integrative Analysis of Transcriptome-Wide Association Study and Messenger RNA Expression Profile.

Amyotrophic lateral sclerosis, a fatal neurodegeneration disease affecting motor neurons in the brain and spinal cord, is difficult to diagnose and treat. The objective of this study is to identify novel candidate genes related to ALS. Transcriptome-wide association study of ALS was conducted by integrating the genome-wide association study summary data (including 1234 ALS patients and 2850 controls) and pre-computed gene expression weights of different tissues. The ALS-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the mRNA expression profiles of the sporadic ALS. Functional enrichment and annotation analysis of identified genes were performed by an R package and the functional mapping and annotation software. TWAS identified 761 significant genes (PTWAS < 0.05), 627 Gene ontology terms, and 8 Kyoto Encyclopedia of Genes and Genomes pathways for ALS, such as C9orf72, with three expression quantitative trait loci were found significantly: rs2453554 (PTWAS CBRS = 4.68 × 10-10, PTWAS CBRS = 2.54 × 10-9), rs10967976 (PTWAS CBRS = 7.85 × 10-10, PTWAS CBRS = 8.91 × 10-9, PTWAS CBRS = 1.49 × 10-7, PTWAS CBRS = 5.59 × 10-7), rs3849946 (PTWAS CBRS = 7.69 × 10-4, PTWAS YBL = 4.02 × 10-2), Mitochondrion (Padj = 4.22 × 10-16), and Cell cycle (Padj = 2.04 × 10-3). Moreover, 107 common genes, 4 KEGG pathways and 41 GO terms were detected by integrating mRNA expression profiles of sALS, such as CPVL (FC = 2.06, PmRNA = 6.99 × 10-6, PTWAS CBR = 2.88 × 10-2, PTWAS CBR = 4.37 × 10-2), Pyrimidine Metabolism (Padj = 2.43 × 10-2), and Cell Activation (Padj = 5.54 × 10-3). Multiple candidate genes and pathways were detected for ALS. Our findings may provide novel clues for understanding the genetic mechanism of ALS.

[Analysis of clinical features of vestibular migraine].

Objective:To analyze the clinical features of Vestibular migraine（VM） and provide evidence for its accurate diagnosis and medical identification of flight personnel. Method:A total of 490 samples of VM patients were collected. Among them, 88 samples were secondary to benign paroxysmal positional vertigo（BPPV）, and 11 samples were co-occurring with Meniere's disease（MD）. All patients received drugs, lifestyle management, vestibular rehabilitation and other comprehensive treatment, and analyzed the clinical features and effect within 6 months. Result:①The male-female ratio of VM patients was 1∶1.95, the average age was （50.2±14.3） years old, （48.7±15.0） years old for males and （51.0±13.9） years old for females. No statistically significant differences were found（P>0.05）. The average duration was（54.5±84.8） months, （35.0±59.0） months for males and（64.7±94.0） months for females. The difference was statistically significant（P<0.05）. ②The main clinical symptoms are dizziness, migraine or previous history of migraine, fear of sound/noisy environment sensitivity, photophobia/visual sensitivity, nausea/vomiting, vestibular posture symptoms, tinnitus, hearing loss, etc. , diarrhea during dizziness or headache was one special symptom of VM; ③The abnormal rate of vestibular autorotation test（VAT） in 118 VM patients was 72.3%, while the abnormal rate of caloric test in 170 VM patients was 32.9%; ④The effective remission rate within 6 months of VM patients with secondary BPPV and MD was 78.6% and 83.4%, while the VM patients without secondary benign paroxysmal positional vertigo（BPPV） and Meniere's disease（MD） was 93.3%. The difference was statistically significant（P<0.05）. Conclusion:The clinical manifestations of VM patients were various. Female VM patients had higher incidence, the course of disease than male VM patients, diarrhea can be regarded as one of the clinical features distinguished from MD. The abnormal rate of VAT was higher in the common clinical examiniations of VM patients. VM patients treatment should focus on personalized prescription and lifestyle management, vestibular rehabilitation, and corresponding treatment at the same time should be given to patients with secondary BPPV and MD to improve the efficacy. The medical identification of flight personnel VM patients should be strictly controlled, pilots should be grounded, while flight combat personnel and flight technical personnel need chartered medical identification.

[Magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution sequence for obstructive hydrocephalus: impact on diagnosis and surgical strategy modification].

OBJECTIVE: To investigate the value of magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution (3D-SPACE) sequences in diagnosis and surgical strategy modification for obstructive hydrocephalus. METHODS: From March 2013 to July 2014, there were 152 cases admitted in People's Liberation Army General Hospital suffered from hydrocephalus, including 88 male patients and 64 female patients aging from 8 months to 79 years. All patients were performed magnetic resonance T2WI and 3D-SPACE sequence scanning before operation. Surgical strategy was made after evaluation of 3D-SPACE sequence. Non-communicating hydrocephalus was treated with endoscopic third ventriculostomy (ETV) and communicating hydrocephalus was treated with ventriculo-peritoneal shunt. According to MR images of direct observation to site of obstruction to determine the detection rate. MRI 3D-SPACE and cranial CT examination were performed in regular follow-up studies. RESULTS: The relevance ratio of 3D-SPACE for the diagnosis of non-communicating hydrocephalus was 98.3% (114/116), while the relevance ratio of conventional T2-weighted MRI was 72.4% (84/116). Among the 152 patients, there were 36 cases with cerebral aqueduct film obstruction, 22 cases with space-occupying lesions in pineal region, posterior part of the third ventricle, or space-occupying lesions in quadrigeminal bodies area, 10 cases with Dandy-Walker symptom, 18 cases with cyst of the anterior pool of the bridge, 16 cases with cysticercosis, 4 cases with cyst of lateral ventricle, 2 cases with cyst of fourth ventricle, 2 cases with space-occupying lesion in foramen ofmonro, 2 cases with foramen ofmonro atresia, 4 cases with craniopharyngioma, 36 cases with communicating hydrocephalus. There were 112 hydrocephalus cases (73.7%) were treated with ETV, without shunt catheter insertion in follow-up study from 1 to 18 months (average (14±9) months). CONCLUSIONS: For obstructive hydrocephalus, MRI 3D-SPACE sequence image has high diagnostic yield rate for providing more detailed anatomical information than conventional MRI. Hence, the advanced imaging methods are helpful for surgical treatment strategy decision making.