The correlation between transcription factor 7-like 2 gene polymorphisms and susceptibility of gestational diabetes mellitus in the population of central China: A case-control study.

Objective: To investigate the correlation between transcription factor 7-like 2 (TCF7L2) gene polymorphisms and gestational diabetes mellitus (GDM) risk in the central Chinese population. Methods: This case-control study examined the association of seven TCF7L2 gene single-nucleotide polymorphisms (SNPs) (rs11196218, rs4506565, rs7895340, rs7901695, rs11196205, rs12243326, and rs290487) with GDM risk in the central Chinese population (843 GDM and 877 controls). The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test, Fisher's exact test, and logistic regression were performed. Results: Differences in age, pre-pregnant body mass index (BMI), and family history of type 2 diabetes mellitus (T2DM) between the case and control groups were significant (p < 0.05). Compared with the wild-type genotype, pregnant women with genotypes of rs4506565-AT (OR = 1.89, 95%CI: 1.18-3.02), rs7895340 GA (OR = 1.93, 95%CI: 1.06-3.54), rs7901695-TC (OR = 1.79, 95%CI: 1.11-2.88), and rs11196205-GC (OR = 2.15, 95%CI: 1.16-3.98) had a significantly higher risk of GDM, adjusted by age, pre-pregnant BMI, and family history of T2DM. Functional annotation showed that all these four SNPs fell in the functional elements of human pancreatic islets. Further cumulative effects analysis concluded that when participants carried all these four risk genotypes, the risk of GDM was 3.51 times (OR = 3.51, 95%CI: 1.38-8.90) than that of those without any risk genotypes. Conclusions: The findings of this study suggested that rs4506565, rs7895340, rs7901695, and rs11196205 were the genetic susceptibility SNPs of GDM in the central Chinese population. Further studies are needed to validate our findings and clarify the underlying mechanisms.

Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China.

BACKGROUND: Gestational diabetes mellitus (GDM) increased risk of perinatal complications for both the women and the fetuses. The association between the vitamin D receptor (VDR) gene polymorphism and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. Moreover, we aimed to explore their combined effects on the risk of GDM. METHODS: Pregnant women who had prenatal examinations at 24 to 28 weeks' gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and associations with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM. RESULTS: Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs. CONCLUSIONS: The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.

The correlation between plasma total homocysteine level and gestational diabetes mellitus in a Chinese Han population.

To assess the correlation between plasma total homocysteine (tHcy) level and gestational diabetes mellitus (GDM) in a Chinese Han population. This case-control study included 350 GDM patients and 346 gestational week-matched normal glucose tolerance (NGT) pregnant women. Plasma tHcy and insulin levels were analyzed by HPLC and ELISA respectively. Logistic regression analysis was used to investigate the correlation between plasma tHcy level and risk of GDM. Women with GDM had a higher plasma tHcy level than NGT women (6.61 ± 1.32 vs. 6.17 ± 1.29 µmol/L, P = 0.001)). The GDM risk was 1.79 (OR = 1.79, 95% CI 1.18-2.72, P = 0.006) times higher in women whose plasma tHcy level was ≥ 7.29 µmol/L compared to women with plasma tHcy level < 5.75 µmol/L. Stratified analysis showed the GDM risk were much higher when HOMA-IR index ≥ 2 (OR = 5.42, 95% CI 2.51-11.74, P < 0.001), age ≥ 30 years (OR = 5.14, 95% CI 2.78-9.52, P < 0.001), or women with a family history of type 2 diabetes mellitus (T2DM) (OR = 4.13, 95% CI 1.78-9.56, P = 0.001). In the Chinese Han population, an elevated plasma tHcy level may increase the overall risk of GDM especially in women with a high HOMA-IR index, increasing age or with family history of T2DM.

Epidemiology of COVID-19 in older persons, Wuhan, China.

BACKGROUND: the epidemiological characteristics of older patients with COVID-19 was far from clear. OBJECTIVE: to explore the epidemiology of older patients with COVID-19 in Wuhan, China. DESIGN: a retrospective cross-sectional study. SETTING: a population-based study. SUBJECTS: the resident older patients (>65 years) diagnosed with COVID-19. METHODS: city-wide case series reported to Wuhan Center for Disease Control and Prevention from 12 December 2019 to 17 March 2020 were included. The epidemic curves were constructed by dates of disease onset. RESULTS: 14,238 confirmed COVID-19 cases were older persons. The number of male cases were slightly less than female cases (1:1.01). The attack rate of COVID-19 in the older persons was 11.49‰ in Wuhan. There was a rapid increase of disease at the early stage of the epidemic and then a gradual and steady decrease was performed. 3,723 (26.15%) and 734 (5.16%) patients were diagnosed as severe and critical cases, respectively. The attributable crude fatality ratio of COVID-19 in the older population was 222.57/100,000, and the crude fatality ratio of COVID was 19.37%. The proportion of severe and critical cases, and fatality ratio were both higher in downtown area and increased with age. CONCLUSIONS: the older persons are sensitive to COVID-19. The proportion of severe and critical cases and fatality ratio are higher than that in children and younger adults. Strengthen the protection and control strategies for the older adults are of priorities. More detailed epidemiological and clinical information should be measured in further studies.

Relationships between functional fitness and cognitive impairment in Chinese community-dwelling older adults: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the associations between each functional fitness (FF) domain and cognitive impairment (CI) in Chinese community-dwelling older adults. DESIGN: A community-based, cross-sectional study was conducted. SETTING: Participants were selected by multistage stratified random sampling in Wuhan City, Hubei Province, Central China, during December 2015-May 2016. PARTICIPANTS: A total of 2096 (1031 male and 1065 female) adults older than 65 years were included in our study. Exclusion criteria were age <65 years, losing self-living ability, previously diagnosed with dementia by a neurological physician, severe physical pain, congestive heart failure, dizziness and uncontrolled hypertension (exceeding 160/100 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The Senior Fitness Test and the Mini-Mental State Examination were used to measure FF (including 30 s chair stand, 30 s arm curl, 2 min step, 8 foot up-and-go, chair sit-and-reach and back scratch) and screen CI, respectively. Activities of daily living and instrumental activities of daily living questionnaires were administered to evaluate functional status (FS). RESULTS: 32.16% were classified as the CI group. The results showed that the CI group had significantly lower frequency of 30 s chair stand, 30 s arm curl and 2 min step, and longer time to complete the 8 foot up-and-go, shorter chair sit-and-reach and back scratch distance than the non-CI adults (p<0.05). Except for back scratch, older adults with moderate and high levels of FF were less likely to have CI than those with low levels, adjusted by sociodemographics, chronic disease, health condition, health behaviour and FS (p<0.05). CONCLUSIONS: The relationship between FF and CI was independent of FS decline in Chinese community-dwelling older people.

Double-stranded RNA analog and type I interferon regulate expression of Trem paired receptors in murine myeloid cells.

BACKGROUND: Triggering receptors expressed on myeloid cells (Trem) proteins are a family of cell surface receptors used to control innate immune responses such as proinflammatory cytokine production in mice. Trem genes belong to a rapidly expanding family of receptors that include activating and inhibitory paired-isoforms. RESULTS: By comparative genomic analysis, we found that Trem4, Trem5 and Trem-like transcript-6 (Treml6) genes typically paired receptors. These paired Trem genes were murine-specific and originated from an immunoreceptor tyrosine-based inhibition motif (ITIM)-containing gene. Treml6 encoded ITIM, whereas Trem4 and Trem5 lacked the ITIM but possessed positively-charged residues to associate with DNAX activating protein of 12 kDa (DAP12). DAP12 was directly associated with Trem4 and Trem5, and DAP12 coupling was mandatory for their expression on the cell surface. In bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs), and splenic DC subsets, polyinosinic-polycytidylic acid (polyI:C) followed by type I interferon (IFN) production induced Trem4 and Treml6 whereas polyI:C or other TLR agonists failed to induce the expression of Trem5. PolyI:C induced Treml6 and Trem4 more efficiently in BMDMs than BMDCs. Treml6 was more potentially up-regulated in conventional DC (cDCs) and plasmacytoid DC (pDCs) than Trem4 in mice upon in vivo stimulation with polyI:C. DISCUSSION: Treml6-dependent inhibitory signal would be dominant in viral infection compared to resting state. Though no direct ligands of these Trem receptors have been determined, the results infer that a set of Trem receptors are up-regulated in response to viral RNA to regulate myeloid cell activation through modulation of DAP12-associated Trem4 and ITIM-containing Treml6.

Down-regulation of EBV-LMP1 radio-sensitizes nasal pharyngeal carcinoma cells via NF-κB regulated ATM expression.

BACKGROUND: The latent membrane protein 1 (LMP1) encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previous studies we experimentally demonstrated that down-regulation of LMP1 expression by DNAzymes could increase radiosensitivity both in cells and in a xenograft NPC model in mice. RESULTS: In this study we explored the molecular mechanisms underlying the radiosensitization caused by the down-regulation of LMP1 in nasopharyngeal carcinoma. It was confirmed that LMP1 could up-regulate ATM expression in NPCs. Bioinformatic analysis of the ATM ptomoter region revealed three tentative binding sites for NF-κB. By using a specific inhibitor of NF-κB signaling and the dominant negative mutant of IkappaB, it was shown that the ATM expression in CNE1-LMP1 cells could be efficiently suppressed. Inhibition of LMP1 expression by the DNAzyme led to attenuation of the NF-κB DNA binding activity. We further showed that the silence of ATM expression by ATM-targeted siRNA could enhance the radiosensitivity in LMP1 positive NPC cells. CONCLUSIONS: Together, our results indicate that ATM expression can be regulated by LMP1 via the NF-κB pathways through direct promoter binding, which resulted in the change of radiosensitivity in NPCs.