Top 100 influential manuscripts in obstructive sleep apnea: a bibliometric analysis.

OBJECTIVE: This study aimed to explore the characteristics of the top 100 influential manuscripts on obstructive sleep apnea (OSA). METHODS: All manuscripts in English were searched from the Thomson Reuters Web of Science database by using OSA-related terms and ranked based on citation frequency. The top 100 influential manuscripts were selected and further analyzed by author, subject, journal, year of publication, country of origin, and institution. RESULTS: A total of 42,878 manuscripts were searched from the Web of Science. The top 100 influential manuscripts were published from 2005 to 2017, with a total citation frequency of 38,463 and a median citation frequency of 303 (range: from 210 to 2, 707). The American Journal of Respiratory and Critical Care Medicine published the largest number of manuscripts from the top 100 (n = 18; 5340 citations), followed by Sleep (n = 11; 3516 citations) and Chest (n = 7; 1784 citations). The most cited manuscript (Marin, J.M et al., Lancet 2005; 2707 citations) mainly analyzed long-term cardiovascular outcomes in men with OSA with/without continuous positive airway pressure. The most prevalent subject was associated diseases (n = 41), followed by treatments (n = 40). Most of the manuscripts were original articles (n = 63) based on observational clinical studies and published from American institutions (n = 60). CONCLUSIONS: Our study identified the top 100 influential manuscripts on OSA and provides insights into the characteristics of the most highly cited manuscripts to improve our understanding and management of OSA.

Association between ERα gene Pvu II polymorphism and breast cancer susceptibility: A meta-analysis.

BACKGROUND: Estrogen has played an important role in the development of breast cancer. ER-α PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently. METHODS: PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case-control studies on association between ERα gene Pvu II polymorphism and breast cancer risk published before September 1, 2017. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literatures, Stata 14.0 software was applied for meta-analysis, and the pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The subgroup analysis was performed to assess the confounding factors, followed by assessment of publication bias and sensitivity analysis. RESULTS: A total of 26 studies were enrolled in the analysis based on inclusion criteria, which included 15,360 patients and 26,423 controls. The results demonstrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in 3 genetic models (C vs T, OR = 0.962, 95% CI = 0.933-0.992, P = .012; CC vs TT, OR = 0.911, 95% CI = 0.856-0.969, P = .003; CC vs TT/CT, OR = 0.923, 95% CI = 0.874-0.975, P = .004). Subgroup analysis was conducted on the basis of ethnicity and source of controls, whose results illustrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in Asians rather than in Caucasians (CC vs TT, OR = 0.862, 95% CI = 0.750-0.922, P = .038; CC vs TT/CT, OR = 0.851, 95% CI = 0.755-0.959, P = .008). In population-based subgroup rather than in hospital-based subgroup, ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in the allele model, homozygous model, dominant model, and recessive model (C vs T, OR = 0.943, 95% CI = 0.911-0.977, P = .001; CC vs TT, OR = 0.878, 95% CI = 0.817-0.944, P = .000; CC/CT vs TT, OR = 0.936, 95% CI = 0.881-0.994, P = .031; CC vs TT/CT, OR = 0.902, 95% CI = 0.847-0.960, P = .001). CONCLUSION: ERα gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway.

DNAX-activating protein of 12 kDa (DAP12) is a signaling adapter protein expressed in cells that participate in innate immune responses. By pairing with different triggering receptors expressed on myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular responses. In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator. TREM2 has also been shown to stimulate the phagocytosis of apoptotic neurons and define the barrier function in microglia. Notably, loss-of-function mutations of either DAP12 or TREM2 result in a disorder known as Nasu-Hakola disease (NHD); and mutations of these genes have been associated with the risk for Alzheimer's disease (AD), suggesting that TREM2 and DAP12 may regulate common signaling pathways in the disease pathogenesis. In this study, we demonstrated an anti-inflammatory role of DAP12 in murine microglia that depends on the presence of TREM2. We also uncovered the JNK signaling pathway as the underlying molecular mechanism by which the TREM2/DAP12 complex suppresses the hyperactivation of microglia upon LPS stimulation. Interestingly, LPS down-regulates the expression of Trem2 via the activation of JNK and NF-κB signaling pathways, resulting in a vicious cycle that synergistically promotes the inflammatory responses. Our study provides insights into mechanism-based therapy for neuroinflammatory disorders.

Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P<0.05). The APOE ε3 group had slightly higher abnormal fasting plasma glucose values than did the APOE ε2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes.

Demographic and Lifestyle Characteristics, but Not Apolipoprotein E Genotype, Are Associated with Intelligence among Young Chinese College Students.

BACKGROUND: Intelligence is an important human feature that strongly affects many life outcomes, including health, life-span, income, educational and occupational attainments. People at all ages differ in their intelligence but the origins of these differences are much debated. A variety of environmental and genetic factors have been reported to be associated with individual intelligence, yet their nature and contribution to intelligence differences have been controversial. OBJECTIVE: To investigate the contribution of apolipoprotein E (APOE) genotype, which is associated with the risk for Alzheimer's disease, as well as demographic and lifestyle characteristics, to the variation in intelligence. METHODS: A total of 607 Chinese college students aged 18 to 25 years old were included in this prospective observational study. The Chinese revision of Wechsler Adult Intelligence Scale (the fourth edition, short version) was used to determine the intelligence level of participants. Demographic and lifestyle characteristics data were obtained from self-administered questionnaires. RESULTS: No significant association was found between APOE polymorphic alleles and different intelligence quotient (IQ) measures. Interestingly, a portion of demographic and lifestyle characteristics, including age, smoking and sleep quality were significantly associated with different IQ measures. CONCLUSIONS: Our findings indicate that demographic features and lifestyle characteristics, but not APOE genotype, are associated with intelligence measures among young Chinese college students. Thus, although APOE ε4 allele is a strong genetic risk factor for Alzheimer's disease, it does not seem to impact intelligence at young ages.

DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a DAP12-associated receptor expressed in microglia, macrophages, and other myeloid-derived cells. Previous studies have suggested that TREM2/DAP12 signaling pathway reduces inflammatory responses and promotes phagocytosis of apoptotic neurons. Recently, TREM2 has been identified as a risk gene for Alzheimer disease (AD). Here, we show that DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a substrate for γ-secretase. Co-expression of DAP12 with TREM2 selectively increased the level of TREM2-CTF with little effects on that of full-length TREM2. The interaction between DAP12 and TREM2 is essential for TREM2-CTF stabilization as a mutant form of DAP12 with disrupted interaction with TREM2 failed to exhibit such an effect. Silencing of either Trem2 or Dap12 gene significantly exacerbated pro-inflammatory responses induced by lipopolysaccharides (LPS). Importantly, overexpression of either full-length TREM2 or TREM2-CTF reduced LPS-induced inflammatory responses. Taken together, our results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.