Background: Although an increasing number of common variants contributing to Alzheimer’s disease (AD) are uncovered by genome-wide association studies, they can only explain less than half of the heritability of AD. Rare variant association studies (RVAS) has become an increasingly important area to explain the risk or trait variability of AD. Method: To investigate the potential rare variants that cause AD, we screened 70,209 rare variants from two cohorts of a 175 AD cohort and a 214 cognitively normal cohort from the Alzheimer’s Disease Neuroimaging Initiative database. MIRARE, a novel RVAS method, was performed on 232 non-synonymous variants selected by ANNOVAR annotation. Molecular docking and molecular dynamics (MD) simulation were adopted to verify the interaction between the chosen functional variants and BACE1. Results: MIRAGE analysis revealed significant associations between AD and six potential pathogenic genes, including PREX2, FLG, DHX16, NID2, ZnF585B and ZnF875. Only interactions between FLG (including wild type and rs3120654(SER742TYR)) and BACE1 were verified by molecular docking and MD simulation. The interaction of FLG(SER742TYR) with BACE1 was greater than that of wildtype FLG with BACE1. Conclusions: According to the literature search, bio-informatics analysis, and molecular docking and MD simulation, we find non-synonymous rare variants in six genes, especially FLG(rs3120654), that may play key roles in AD.

Background: Erector spinae plane (ESP) block has been reported to provide analgesia in spine surgery in case reports or case series, and there have been no controlled studies to date evaluating its efficacy. We aimed to exam the roles of ESP block in lumbar surgery in a single center randomized control trial by injecting local analgesic into the interfacial plane between the erector spinae muscles and the transverse process under ultrasound guidance. Methods: Consecutive elective lumbar surgery patients were randomized into either a control group (general anesthesia only, Group G, N=32) or a treatment group (general anesthesia plus ESP block, Group E, N=30). Several parameters including visual analog scale (VAS, primary outcome), perioperative anesthetics and analgesics usage, indexes of hemodynamics variation, return of bowel function and overall benefit of analgesia score (OBAS) were measured. Results: Significant differences in VAS scores over time were found between the two matched groups (P = 0.010). Group E patients had significantly lower pain scores than Group G patients in the early postoperative period within the first 6 hr. Group G and Group E VAS scores peaked at 1 hr and 12 hr, respectively, and the peak pain score in Group G is significantly higher than that of Group E (P = 0.002). In addition, patients who received ESP block had lower perioperative analgesic and sedative medication requirements, improved satisfaction with pain management, more stable hemodynamics, and earlier bowel function return than those using general anesthesia alone. Conclusion: Pre-incision bilateral single injection ESP blocks provided effective analgesia perioperatively during lumbar laminoplasty, decreased perioperative anesthesia and analgesia requirement, and accelerated short-term recovery.