Backgrounds and objectivesCurrently, no consensus has been reached on the therapeutic implications of monoclonal antibodies against amyloid-beta (Aβ) in Alzheimer's disease (AD). This study aimed to examine the effectiveness and safety of monoclonal antibodies against Aβ as a whole and also to determine the superiority of individual antibodies vis-à-vis placebo in mild or moderate AD.MethodsLiterature retrieval, article selection, and data abstraction were performed independently and in duplicate. Cognition and function were appraised by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Effect sizes are expressed as standardized mean difference (SMD) with a 95% confidence interval (CI).ResultsTwenty-nine articles involving 108 drug-specific trials and 21,383 participants were eligible for synthesis. Of the four assessment scales, only CDR-SB was significantly reduced after using monoclonal antibodies against Aβ relative to placebo (SMD: −0.12; 95% CI: −0.2 to −0.03; p = 0.008). Egger's tests indicated a low likelihood of publication bias. At individual levels, bapineuzumab was associated with a significant increase in MMSE (SMD: 0.588; 95% CI: 0.226–0.95) and DAD (SMD: 0.919; 95% CI: 0.105–1.943), and a significant decrease in CDR-SB (SMD: −0.15; 95% CI: −0.282–0.018). Bapineuzumab can increase the significant risk of serious adverse events (OR: 1.281; 95% CI: 1.075–1.525).ConclusionOur findings indicate that monoclonal antibodies against Aβ can effectively improve instrumental activities of daily life in mild or moderate AD. In particular, bapineuzumab can improve cognition and function, as well as activities of daily life, and meanwhile, it triggers serious adverse events.

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ObjectivesThis meta-analysis aimed to test the association of angiotensin-converting enzyme (ACE) gene I/D polymorphism with asthma risk and circulating ACE changes.MethodsPublic literature retrieval, publication selection, and information extraction were completed independently by two investigators. Effect-size values are expressed as odds ratios (ORs) or standardized mean differences (SMDs) with a 95% confidence interval (95% CI).ResultsNineteen studies (2,888 patients and 9,549 controls) fulfilled the eligibility criteria. Overall investigations demonstrated that ACE gene I/D polymorphism was significantly associated with asthma risk under allelic (OR, 95% CI: 1.26, 1.08 to 1.48), homozygous genotypic (1.50, 1.09 to 2.06), and recessive (1.53, 1.24 to 1.89) models with moderate heterogeneity (I2 statistic: 64% to 79%). Subsidiary investigations recorded that race, matched status, asthma diagnosis, sample size, and age possibly accounted for the existence of significant heterogeneity. Relative to carriers with the II genotype, those with the DD genotype, ID genotype, and the combination of DD and ID genotypes had significantly higher concentrations of circulating ACE (WMD: 3.13, 2.07, and 2.83 U/L, respectively, p < 0.05). Adoption of Mendelian randomization analyses revealed that one unit increment in circulating ACE concentrations was found to be significantly associated with a 1.14-fold increased risk of asthma (95% CI: 1.02 to 4.24).ConclusionWe provided strong meta-analytical evidence supporting the causal implication of high circulating ACE concentrations in the development of asthma.

Objective Charcot –Marie–Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population. Methods With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing. Results We identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1, all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified with the most common mutation c.754C>T p. R252W, suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module.Conclusions Our study confirmed that MORC2-related neuropathies exist in the Chinese population, as a relatively high mutation rate. We revealed a complex genotype-phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms.