Previous studies have indicated that statins use is associated with risk of dementia, but presented controversial results. Medline, Embase, Web of Science, and the Cochrane Database were searched update to November 2017 to identify the potential relationship between statins use and dementia. Thirty-one eligible studies involving a total of 3332,706 participants with 184,666 incident cases were included in this meta-analysis. Statins use was associated with dementia risk decrement (relevant risk [RR]: 0.85; 95% confidence interval [CI], 0.80-0.89). Subgroup analysis showed statins use was associated with Alzheimer disease (AD) (RR: 0.81; 95% CI, 0.73-0.89) and non-AD dementia (RR: 0.81; 95% CI, 0.73-0.89) risk decrement. Furthermore, statins use was associated with dementia risk decrement in female (RR: 0.89; 95% CI, 0.80-0.98) and male (RR: 0.88; 95% CI, 0.83-0.93). In addition, a dose-response showed per 1 year of duration of statins use incremental increase was associated with 20% dementia risk decrement (RR: 0.80; 95% CI, 0.73-0.87), and per 5-mg mean daily dose incremental increase in statins use was associated with 11% dementia risk decrement (RR: 0.89; 95% CI, 0.83-0.96). Statins use was associated with dementia risk decrement. The potency and the cumulative duration of statin utilized played critical roles.

Objectives The aim of this network meta-analysis is to assess the effectiveness of therapeutic strategies for patients with radiculopathy, including physical, medical, surgical, and other therapies. Methods We electronically searched electronic databases including PubMed and Embase for randomized controlled trials. The response rate and visual analog scale of pain change were considered as primary outcomes. The outcomes were measured by odds ratio (OR) value and corresponding 95% credible intervals (CrIs) or standardized mean difference (MD) with 95% CrIs. Besides, surface under cumulative ranking curve (SUCRA) were performed to rank efficacy and safety of treatments on each end points. Results A total of 16 eligible studies with 1071 subjects were included in this analysis. Our results showed that corticosteroid was significantly more effective than control regarding the response rate (OR = 3.86, 95% CrI: 1.16, 12.55). Surgery had a better performance in pain change compared with control (MD = -1.92, 95% CrI: -3.58, -0.15). According to the SUCRA results, corticosteroid, collar, and physiotherapy ranked the highest concerning response rate (SUCRA = 0.656, 0.652, and 0.610, respectively). Surgery, traction, and corticosteroid were superior to others in pain change (SUCRA = 0.866, 0.748, and 0.589, respectively). Conclusion According to the network meta-analysis result, we recommended surgery as the optimal treatment for radiculopathy patients; traction and corticosteroids were also recommended for their beneficial interventions.

Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation.