Identification of SARS-CoV-2 m6A modification sites correlate with viral pathogenicity.

It has recently been found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) m6A modifications can affect viral replication and function. However, no studies to date have shown a correlation between SARS-CoV-2 m6A modifications and viral pathogenicity. In this study, we analyzed m6A modification in 2,190,667 SARS-CoV-2 genomic RNAs. m6A modifications of SARS-CoV-2 from different lineages, causing mild or severe COVID-19 and showing breakthrough for different vaccines were analyzed to explore correlations with viral pathogenicity. The results suggested that the presence of more m6A modifications in the SARS-CoV-2 N region (positive strand) correlates with weaker pathogenicity. In addition, we identified three m6A modification sites correlating with weak pathogenicity (924 in ORF1ab, 15,659 in ORF1ab, 28,288 in N, 28,633 in N and 29,385 in N, 29,707 in 3'UTR) and one with strong pathogenicity (74 in 5'UTR). These results provide new information for understanding the prevalence of SARS-CoV-2 and controlling the virus.

MAN5, a Glycosyl Hydrolase Superfamily Protein, Is a Key Factor Involved in Cyanide-Promoted Seed Germination in Arabidopsis thaliana.

Seed germination is the complex adaptive trait of higher plants influenced by a large number of genes and environmental factors. Numerous studies have been performed to better understand how germination is controlled by various environmental factors and applied chemicals, such as cyanide. However, still very little is known about the molecular mechanisms of how extrinsic signals regulate seed germination. Our and previous studies found that non-lethal cyanide treatment promotes seed germination, but the regulatory mechanism is unclear. In this study, we found that a low concentration of cyanide pretreatment significantly enhanced the expression of endo-ß-mannanase 5 (MAN5) gene in Arabidopsis thaliana, and the mutation of this gene impaired cyanide-mediated seed germination. In contrast, overexpression of MAN5 gene enhanced Arabidopsis seed germination ability under both normal and salt stress conditions. Further studies showed that the expression of the MAN5 gene was negatively regulated by ABA insensitive 5 (ABI5); In abi5 mutant seeds, the expression of the MAN5 gene was increased and the seed germination rate was accelerated. Additionally, cyanide pretreatment markedly reduced the gene expression of ABI5 in Arabidopsis seeds. Taken together, our data support the involvement of MAN5 as a key gene in cyanide-mediated seed germination and confirm the role of ABI5 as a critical negative factor involved in cyanide-regulated MAN5 gene expression.

Correlation between neutrophil gelatinase phase lipocalin and cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. Methods: The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. Results: A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Conclusion: Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.

CircRNAs in tumor immunity and immunotherapy: Perspectives from innate and adaptive immunity.

Tumor immunotherapy is a new therapeutic approach that has been evolving in the last decade and has dramatically changed the treatment options for cancer. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with high stability, tissue-specific and cell-specific expression. There is growing evidence that circRNAs are involved in the regulation of both adaptive and innate immunity. They play important roles in tumor immunotherapy by affecting macrophage, NK and T cell function. The high stability and tissue specificity make them ideal candidate biomarkers for therapeutic effects. CircRNAs also represent one of promising targets or adjuvant for immunotherapy. Investigations in this field progress rapidly and provide essential support for the diagnosis, prognosis and treatment guidance of cancers in the future. In this review, we summarize the role of circRNAs on tumor immunity from the viewpoint of innate and adaptive immunity, and explore the role of circRNAs in tumor immunotherapy.

The role of cyanoalanine synthase and alternative oxidase in promoting salt stress tolerance in Arabidopsis thaliana.

BACKGROUND: Cyanide is a toxic chemical that inhibits cellular respiration. In plants, cyanide can be produced by themselves, especially under stressful conditions. Cyanoalanine synthase (CAS) is a key enzyme involved in plant cyanide detoxification. There are three genes encoding CAS in Arabidopsis thaliana, but the roles of these genes in the plant's response to stress are less studied. In addition, it is known that alternative oxidase (AOX) mediates cyanide-resistant respiration, but the relationship between CAS and AOX in regulating the plant stress response remains largely unknown. RESULTS: Here, the effects of the overexpression or mutation of these three CAS genes on salt stress tolerance were investigated. The results showed that under normal conditions, the overexpression or mutation of the CAS genes had no significant effect on the seed germination and growth of Arabidopsis thaliana compared with wild type (WT). However, under 50, 100, and 200 mM NaCl conditions, the seeds overexpressing CAS genes showed stronger salt stress resistance, i.e., higher germination speed than WT seeds, especially those that overexpressed the CYS-C1 and CYS-D1 genes. In contrast, the seeds with CAS gene mutations exhibited salt sensitivity, and their germination ability and growth were significantly damaged by 100 and 200 mM NaCl. Importantly, this difference in salt stress resistance became more pronounced in CAS-OE, WT, and mutant seeds with increasing salt concentration. The CAS-OE seeds maintained higher respiration rates than the WT and CAS mutant seeds under salt stress conditions. The cyanide contents in CAS mutant seeds were approximately 3 times higher than those in WT seeds and more than 5 times higher than those in CAS-OE seeds. In comparison, plants overexpressing CYS-C1 had the fastest detoxification of cyanide and the best salt tolerance, followed by those overexpressing CYS-D1 and CYS-D2. Furthermore, less hydrogen sulfide (H2S) was observed in CAS-OE seedlings than in WT seedlings under long-term salt stress conditions. Nonetheless, the lack of AOX impaired CAS-OE-mediated plant salt stress resistance, suggesting that CAS and AOX interact to improve salt tolerance is essential. The results also showed that CAS and AOX contributed to the reduction in oxidative damage by helping maintain relatively high levels of antioxidant enzyme activity. CONCLUSION: In summary, the findings of the present study suggest that overexpression of Arabidopsis CAS family genes plays a positive role in salt stress tolerance and highlights the contribution of AOX to CAS-mediated plant salt resistance, mainly by reducing cyanide and H2S toxicity.

A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. METHODS: This was a large­scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10- 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy. CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients. TRIAL REGISTRATION NUMBER: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .

Long-term effects of early stress due to earthquake exposure on depression symptoms in adulthood: a cross-sectional study.

OBJECTIVE: This study aimed to investigate the long-term effects of early stress by Tangshan earthquake on symptoms of depression in adulthood. METHOD: A total of 1534 volunteers born and raised in Tangshan were investigated; finally, 1328 subjects were enrolled in the study. They were divided into three groups according to their birth dates: infant exposure, prenatal exposure, and non-exposure. The questionnaires and psychological evaluation of all subjects were completed using a one-on-one psychological test. RESULTS: The rate of depressive symptoms in the prenatal exposure group was the highest, and the lowest in the non-exposure group, with statistical differences among the three groups (P = 0.002). Moreover, the incidences of depressed mood, suicide ideation and work and loss of interest in the prenatal exposure group were significantly higher than those in the infant exposure group and the non-exposure group (P = 0.008, P = 0.001, P = 0.038, respectively). Multiple logistic regression analysis showed that male could be a protective factor for symptoms of depression in adulthood, and earthquake exposure was an important predictor of the incidence of depression symptoms. CONCLUSIONS: Fetal or infancy exposure to earthquake might correlate to depression symptoms in adulthood.

NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease.

OBJECTIVE: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease. METHODS: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD. RESULTS: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%. CONCLUSION: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.

Genetic analysis of the ATP11B gene in Chinese Han population with cerebral small vessel disease.

BACKGROUND: A loss-of-function mutation in ATPase phospholipid transporting 11-B (putative) (ATP11B) gene causing cerebral small vessel disease (SVD) in vivo, and a single intronic nucleotide polymorphism in ATP11B: rs148771930 that was associated with white matter hyperintensities burden in European patients with SVD, was recently identified. Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population. RESULTS: We performed target region sequencing including ATP11B gene in 182 patients with sporadic SVD, and identified five rare variants and two novel variants of ATP11B. A case-control study was then performed in 524 patients and matched 550 controls to investigate the relationship between ATP11B and sporadic SVD in the Chinese Han population. Although none of these variants were significantly associated with SVD in our samples, it is important to mention that we identified a novel variant, p. G238W, which was predicted to be pathogenic in silico. This variant was present in our cohort of patients with an extremely low frequency and was absent in the controls. CONCLUSION: Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population.

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma.

BACKGROUND: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. RESULTS: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10- 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). CONCLUSIONS: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration.

Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZ of 4.98~7.50 L/kg), and systemic clearance (CLZ of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.

New insights into the role of cyanide in the promotion of seed germination in tomato.

BACKGROUND: Cyanide is a natural metabolite that exists widely in plants, and it is speculated to be involved in the regulation of various growth and development processes of plants in addition to being regarded as toxic waste. Previous studies have shown that exogenous cyanide treatment helps to improve seed germination, but the mechanism is still unclear. In this study, tomato (Solanum lycopersicum cv. Alisa Craig) was used as the material, and the effects of cyanide pretreatment at different concentrations on tomato seed germination were investigated. RESULTS: The results showed that exogenous application of a lower concentration of cyanide (10 µmol/L KCN) for 12 h strongly increased the tomato seed germination rate. RNA-Seq showed that compared with the control, a total of 15,418 differentially expressed genes (P<0.05) were obtained after pretreatment with KCN for 12 h, and in the next 12 h, a total of 13,425 differentially expressed genes (P<0.05) were regulated. GO and KEGG analyses demonstrated that exogenous KCN pretreatment was involved in regulating the expression (mainly downregulation) of seed storage proteins, thereby accelerating the degradation of stored proteins for seed germination. In addition, KCN pretreatment was also involved in stimulating glycolysis, the TCA cycle and oxidative phosphorylation. Notably, it is shown that KCN acted on the regulation of plant hormone biosynthesis and perception, i.e., down-regulated the gene expression of ABA biosynthesis and signal transduction, but up-regulated the expression of genes related to GA biosynthesis and response. Consistent with this, plant hormone measurements confirmed that the levels of ABA were reduced, but GA levels were induced after pretreatment with KCN. CONCLUSION: These findings provide new insights into the regulation of seed germination by cyanide, that is cyanide-mediated seed germination occurs in a time- and dose-dependent manner, and is related to the mobilization of energy metabolism and the regulation of some plant hormone signals.

Magnetic α-Fe2O3/Fe3O4 Heterostructure Nanorods: Fabrication and Cytotoxicity to A549 Cells.

The magnetic α-Fe2O3/Fe3O4 heterostructure nanorods were fabricated by an alcohol-solution direct combustion method. The influence of the calcination temperature on the composition and properties of the nanorods was investigated. When the calcination temperature was not greater than 400 °C, the magnetic α-Fe2O3/Fe3O4 heterostructure nanorods were obtained, and the saturation magnetization (Ms) of the magnetic α-Fe2O3/Fe3O4 heterostructure nanorods decreased with the calcination temperature increasing from 250 °C to 400 °C; when the calcination temperature was equal or greater than 450 °C, α-Fe2O3 nanorods were obtained. In addition, the effects of nanorods' concentration, nanorods' constituent, incubation time and magnetic field on A549 cytotoxicity were investigated. The cytotoxicity of the heterostructure nanorods appeared time-dependent and concentration-dependent, and the magnetic field could enhance the cytotoxicity of nanorods to A549.

Alternative Oxidase Inhibition Impairs Tobacco Root Development and Root Hair Formation.

Alternative oxidase (AOX) is the terminal oxidase of the mitochondrial respiratory electron transport chain in plant cells and is critical for the balance of mitochondrial hemostasis. In this study, the effect of inhibition of AOX with different concentrations of salicylhydroxamic acid (SHAM) on the tobacco root development was investigated. We show here that AOX inhibition significantly impaired the development of the main root and root hair formation of tobacco. The length of the main root of SHAM-treated tobacco was significantly shorter than that of the control, and no root hairs were formed after treatment with a concentration of 1 mM SHAM or more. The transcriptome analysis showed that AOX inhibition by 1 mM SHAM involved in the regulation of gene expression related to root architecture. A total of 5,855 differentially expressed genes (DEGs) were obtained by comparing SHAM-treated roots with control. Of these, the gene expression related to auxin biosynthesis and perception were significantly downregulated by 1 mM SHAM. Similarly, genes related to cell wall loosening, cell cycle, and root meristem growth factor 1 (RGF1) also showed downregulation on SHAM treatment. Moreover, combined with the results of physiological measurements, the transcriptome analysis demonstrated that AOX inhibition resulted in excessive accumulation of reactive oxygen species in roots, which further induced oxidative damage and cell apoptosis. It is worth noting that when indoleacetic acid (20 nM) and dimethylthiourea (10 mM) were added to the medium containing SHAM, the defects of tobacco root development were alleviated, but to a limited extent. Together, these findings indicated that AOX-mediated respiratory pathway plays a crucial role in the tobacco root development, including root hair formation.

Complex analysis of the personalized pharmacotherapy in the management of COVID-19 patients and suggestions for applications of predictive, preventive, and personalized medicine attitude.

AIMS: Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Drug therapy is one of the major treatments, but contradictory results of clinical trials have been reported among different individuals. Furthermore, comprehensive analysis of personalized pharmacotherapy is still lacking. In this study, analyses were performed on 47 well-characterized COVID-19 drugs used in the personalized treatment of COVID-19. METHODS: Clinical trials with published results of drugs use for COVID-19 treatment were collected to evaluate drug efficacy. Drug-to-Drug Interactions (DDIs) were summarized and classified. Functional variations in actionable pharmacogenes were collected and systematically analysed. "Gene Score" and "Drug Score" were defined and calculated to systematically analyse ethnicity-based genetic differences, which are important for the safer use of COVID-19 drugs. RESULTS: Our results indicated that four antiviral agents (ritonavir, darunavir, daclatasvir and sofosbuvir) and three immune regulators (budesonide, colchicine and prednisone) as well as heparin and enalapril could generate the highest number of DDIs with common concomitantly utilized drugs. Eight drugs (ritonavir, daclatasvir, sofosbuvir, ribavirin, interferon alpha-2b, chloroquine, hydroxychloroquine (HCQ) and ceftriaxone had actionable pharmacogenomics (PGx) biomarkers among all ethnic groups. Fourteen drugs (ritonavir, daclatasvir, prednisone, dexamethasone, ribavirin, HCQ, ceftriaxone, zinc, interferon beta-1a, remdesivir, levofloxacin, lopinavir, human immunoglobulin G and losartan) showed significantly different pharmacogenomic characteristics in relation to the ethnic origin of the patient. CONCLUSION: We recommend that particularly for patients with comorbidities to avoid serious DDIs, the predictive, preventive, and personalized medicine (PPPM, 3 PM) strategies have to be applied for COVID-19 treatment, and genetic tests should be performed for drugs with actionable pharmacogenes, especially in some ethnic groups with a higher frequency of functional variations, as our analysis showed. We also suggest that drugs associated with higher ethnic genetic differences should be given priority in future pharmacogenetic studies for COVID-19 management. To facilitate translation of our results into clinical practice, an approach conform with PPPM/3 PM principles was suggested. In summary, the proposed PPPM/3 PM attitude should be obligatory considered for the overall COVID-19 management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00247-0.

Prevalence and risks of mild cognitive impairment of Chinese community-dwelling women aged above 60 years: A cross-sectional study.

Evidence has shown that risks of cognitive impairment differ between genders. This cross-sectional study sought to determine the prevalence of mild cognitive impairment (MCI) in Chinese community-dwelling women aged above 60 years and identify risks of MCI by multivariate logistic regression analysis. Totally, 1760 Chinese community-dwelling women entered the study. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). MCI was diagnosed by Petersen's criteria. Sociodemographic information, past medical conditions, and age at menopause were screened. The primary study outcome was prevalence of MCI. MCI was diagnosed in 378 (21.5%) women. Older age was a significant risk of MCI (OR 1.621, 95%CI 1.386-1.894; P < 0.001). Low education was associated a 4-fold increase in the risk of MCI (OR 4.036, 95%CI 3.168-5.142). Furthermore, current depression was associated with 2.6-fold increase in the risk of MCI (OR 2.618, 95%CI 1.499-4.587, P = 0.001). Moreover, frequent physical exercise and more leisure and social time activities were associated with significantly reduced risks of MCI, while poor financial status was associated with a significantly increased risk of MCI. Slightly more than 20% of Chinese women aged above 60 years had MCI, and independent risks included older age, low education status, and current depression, highlighting the importance of screening for and removing or minimizing risks of MCI in this specific population.

Prenatal and postnatal exposure to Tangshan earthquake and CRHR1 gene polymorphism influence risk of sleep disturbance in adulthood.

ABSTRACT: To determine the effect of earthquake on sleep quality of adults who had experienced Tangshan Earthquake either as infants or fetuses and also investigate whether CRHR1 polymorphism influenced sleep quality in subjects exposed to seismic stress.Totally 556 subjects were enrolled in the current study and were divided into 3 groups, those who had experienced Tangshan Earthquake as infants (group I) or fetuses (group II), and those who had not experienced Tangshan Earthquake (group III). Sleep was evaluated using the Pittsburgh Sleep Quality Index (PQSI). Three single nucleotide polymorphisms of the CRHR1 gene were analyzed.Fifty two (9.4%) subjects had sleep disturbance, including 17 (9.9%) subjects in group I, 24 (13.4%) subjects in group II, and 11 (5.3%) subjects in group III (χ2 = 7.373, P = .025). Moreover, subjects with CRHR1 genotype T/T had a significantly lower rate of sleep disturbance (7.8%) than subjects with genotype C/T and C/C (14.7%; χ2 = 4.845, P  = .028). Furthermore, subjects with rs7209436 genotype C had an approximately 2-fold increase in the risk of sleep disturbance versus those who were not genotype C (OR = 1.978, 95% CI (1.045, 3.744).Prenatal and postnatal exposure to seismic stress significantly increases subsequent risk of sleep disturbance in adulthood.

Effects of shift work on sleep and cognitive function among male miners.

Shift work is associated with circadian rhythm disruption that manifests in several aspects related to sleep disorder, including trouble falling asleep, shortened sleep, and daytime fatigue. The objective of this study was to investigate the effects of shift work on sleep and cognitive function in the middle-aged male miners in Kailuan Mining Group. From May 2013 to May 2015, male miners were recruited and enrolled in prospective study. The results of PSQI demonstrated that there were significant differences in the total score, subjective sleep quality and sleep duration between two groups. For subjects with education level of senior middle school or below, our results showed that the scores of BVMT-R and HVLT-R in the day shift group were significantly higher than that in the night shift group. According to PSQI score, further test was conducted for HVLT-R and BVMT-R. For subjects with PSQI score≤5, there were significant differences in HVLT-R scores between two groups. In terms of PSQI score>5, BVMT-R scores in the night shift group were significantly lower than that in the day shift group. The workers for night shift work in adulthood would tend to impaired working memory. Education can also influence the performance of working memory.

Experiencing earthquake in the first trimester of the fetal life increases subsequent diabetes risk in the adulthood: a cross-sectional study.

OBJECTIVE: To investigate the long-term effect of prenatal exposure to earthquake stress on diabetes risk in the adulthood. METHODS: This study included employees of Tangshan Kailuan Mining Group between July 29, 1976 and April 28, 1977. The exposure group included subjects who experienced the Tangshan Earthquake during their prenatal period and who had lived in Tangshan since birth. The non-exposure group included subjects who were born 1-1.9 years after the earthquake and who had lived in Tangshan since birth. A questionnaire was designed that included sociodemographic information, conditions during pregnancy, and earthquake experience. Anthropometric measurements including height and weight, body mass index (BMI), waist circumference were made. Fasting plasma glucose (FPG) and lipid profiles were also determined. RESULTS: Totally 947 subjects were included with 397 subjects in the exposed group and 550 subjects in the non-exposed group. The diabetes rate is significant different in these four groups(χ2 =8.045, P = 0.045). Moreover, 11.8, 7.5 and 8.0% of the subjects who were exposed to earthquake in the 1st, 2nd, and 3rd trimester of pregnancy had diabetes. 5.1% of the subjects had diabetes in non-exposure group. Our multivariate analysis showed that 1st trimester (OR 2.481, 95%CI 1.02, 6.034; P = 0.045) and loss of family members during earthquake (OR 2.452, 95%CI 1.293, 4.653; P = 0.006) were associated with significantly increased risk of diabetes. CONCLUSIONS: Exposure to earthquake during the first trimester of pregnancy and experience of family member loss in the earthquake significantly increased the subsequent risk of diabetes in the middle age (36-39 years of age). Our data suggest that earthquake experience in the early pregnancy has a longer-term effect on diabetes risk during adulthood.