Background: Thiamine and riboflavin deficiencies exist to varying degrees worldwide, especially in developing countries. Evidence regarding the association between thiamine and riboflavin intake and gestational diabetes mellitus (GDM) is scarce. Objectives: We aimed to evaluate the association of thiamine and riboflavin intake during pregnancy, including dietary source and supplementation, with GDM risk in a prospective cohort study. Methods: We included 3036 pregnant women (923 in the first trimester and 2113 in the second trimester) from the Tongji Birth Cohort. A validated semi-quantitative food frequency questionnaire and a lifestyle questionnaire were used to assess thiamine and riboflavin intake from dietary source and supplementation, respectively. GDM was diagnosed using the 75 g 2-h oral glucose tolerance test at 24-28 weeks of gestation. A modified Poisson regression or logistic regression model was used to evaluate the association between thiamine and riboflavin intake and GDM risk. Results: Dietary intake of thiamine and riboflavin was at low levels during pregnancy. In the fully adjusted model, compared with participants in quartile 1 (Q1), those who had more total thiamine and riboflavin intake had a lower risk of GDM during the first trimester [thiamine: Q2: RR: 0.58 (95% CI: 0.34, 0.98); Q3: RR: 0.45 (95% CI: 0.24, 0.84); Q4: RR: 0.35 (95% CI: 0.17, 0.72), P for trend = 0.002; riboflavin: Q2: RR: 0.63 (95% CI: 0.37, 1.09); Q3: RR: 0.45 (95% CI: 0.24, 0.87); Q4: RR: 0.39 (95% CI: 0.19, 0.79), P for trend = 0.006]. This association was also observed during the second trimester. Similar results were observed for the association between thiamine and riboflavin supplement use but not dietary intake and GDM risk. Conclusions: Higher intake of thiamine and riboflavin during pregnancy is associated with a lower incidence of GDM.

OBJECTIVE:Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin.METHODS:We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20 weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis.RESULTS:A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM.CONCLUSIONS:Women with a combination of both high plasma ferritin (˃55.7 ng/mL) and high TG (˃1.9 mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk.TRIAL REGISTRATION:This trial is registered at https://ClinicalTrials.gov as NCT03099837.

OBJECTIVE:We evaluated the potential role of maternal serum levels of neutrophils in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). METHODS:This prospective cohort study enrolled singleton pregnant women before gestational weeks 16 and evaluated them until delivery. Among the 1467 pregnant women who performed prenatal care before 14 weeks of gestation in the cohort, a total of 731 were eligible for the final analysis. The associations between neutrophil counts, white blood cell count, neutrophil to lymphocyte ratio, and GDM (assessed by a 75-g oral glucose tolerance test between 24 and 28 weeks) were evaluated by multivariate logistic regression. RESULTS:Neutrophil count outperformed the neutrophil to lymphocyte ratio and white blood cell count in predicting GDM occurrence. We applied a smoothing function and found that neutrophil count was associated with both fasting blood glucose (FBG) (p=.0149) and 1-h postprandial blood glucose (PBG) (p=.0187) after adjustment pre-pregnancy body mass index, family history of diabetes, and age. Logistic regression analysis found that the highest neutrophil count level (6.28-14.73 × 109/L) had a 1.85-fold (95% CI 1.10, 3.09) increased risk of GDM compared with that of the lowest tertile (1.47-4.82 × 109/L). CONCLUSIONS:The results indicated an association between higher neutrophil levels and GDM occurrence.

目的 探讨未成熟网织红细胞比率(IRF)在预测新型冠状病毒肺炎(COVID-19)患者死亡风险中的价值.方法 选取该院2020年1月23日至3月31日确诊的108例COVID-19患者为病例组,其中生存患者88例,死亡患者20例,并以同期进行体检的57例健康者为健康对照组.收集患者的病例资料,比较生存和死亡患者、COVID-19不同临床分型患者网织红细胞绝对值(Ret#)、网织红细胞百分比(Ret％)、高荧光强度网织红细胞比率(HFR)、中荧光强度网织红细胞比率(MFR)、低荧光强度网织红细胞比率(LFR)、IRF.采用受试者工作特征曲线(ROC曲线)和曲线下面积(AUC)评价IRF对COVID-19死亡风险的诊断价值.结果 病例组IRF水平高于健康对照组,差异有统计学意义(P<0.05);死亡组IRF水平高于生存组,差异有统计学意义(P<0.05);IRF诊断COVID-19死亡风险的AUC为0.774(95％CI:0.66～0.89),以IRF=7.90％为诊断COVID-19死亡风险指标的Cut-off值,灵敏度为80.0％,特异度为73.6％.结论 IRF水平是早期预测CO-VID-19患者死亡风险的一个较好的指标.

To retrospectively analyze epidemiological, clinical and hematological characteristics of COVID‐19 patients.

In December 2019, cases of severe coronavirus 2019 (COVID-19) infection rapidly progressed to acute respiratory failure. This study aims to assess the association between the neutrophil-to-lymphocyte ratio (NLR) and the incidence of severe COVID-19 infection. A retrospective cohort study was conducted on 210 patients with COVID-19 infection who were admitted to the Central Hospital of Wuhan from 27 January 2020 to 9 March 2020. Peripheral blood samples were collected and examined for lymphocyte subsets by flow cytometry. Associations between tertiles of NLR and the incidence of severe illness were analysed by logistic regression. Of the 210 patients with COVID-19, 87 were diagnosed as severe cases. The mean NLR of the severe group was higher than that of the mild group (6.6vs.3.3,P< 0.001). The highest tertile of NLR (5.1-19.7) exhibited a 5.9-fold (95% CI 1.3-28.5) increased incidence of severity relative to that of the lowest tertile (0.6-2.5) after adjustments for age, diabetes, hypertension and other confounders. The number of T cells significantly decreased in the severe group (0.5vs.0.9,P< 0.001). COVID-19 might mainly act on lymphocytes, particularly T lymphocytes. NLR was identified as an early risk factor for severe COVID-19 illness. Patients with increased NLR should be admitted to an isolation ward with respiratory monitoring and supportive care.

Background & aims: Emerging evidence has shown the inverse association between dietary polyphenols intake and type 2 diabetes mellitus risk, however, few studies focus on the prospective effects of poly phenols on gestational diabetes mellitus (GDM). Thus, the aim was to evaluate whether higher poly phenols intake and the intake from fruits and vegetables was correlated to a lower risk of GDM. Methods: Dietary intake of polyphenols of women with a singleton pregnancy and without any history of diabetes were obtained by a validated food frequency questionnaire from Tongji Maternal and Child Health Cohort study. Oral glucose tolerance tests were conducted at 24-28 weeks to screen for GDM. Logistic regression models were used to evaluate the association between dietary intake of polyphenols, and the results were presented as odds ratios (ORs) with 95% confidence interval (CIs). Generalized linear models were adopted to determine the association of polyphenols intake with blood glucose concentrations, and the results were presented as coefficients (beta) with 95% CIs. Results: 185 (8.3%) of 2231 pregnant women were diagnosed with GDM. The intake of total polyphenols was 319.9 (217.8-427.0) mg/d, and the intake from fruits and vegetables was 201.6 (115.3-281.8) mg/d and 63.2 (41.1-92.7) mg/d, respectively. Compared with the lowest quartile, the adjusted ORs (95% CIs) of GDM risk for women with the highest quartile of total polyphenols and flavonoids intake was 0.55 (0.30, 0.99), and 0.57 (0.32, 0.99). The adjusted ORs (95% CIs) of GDM risk was 0.55 0.51 (0.30, 0.87) (P-for trend = 0.017) for polyphenols from fruits, 0.58 (0.34, 0.99) (P for trend = 0.038) for flavonoids from fruits, and 0.62 (0.38, 1.00) (P-for trend = 0.065) for anthocyanidins from fruits comparing the highest versus lowest quartile. In addition, each 100 mg increase of total polyphenols and polyphenols from fruits was associated with 0.054 (0.008, 0.096) (P = 0.021) and 0.061 (0.012, 0.109) (P = 0.015) decrease in 2-h post-load blood glucose. No significant association was found between total polyphenols from vegetables intake and the risk of GDM. Conclusions: Higher dietary intake of total polyphenols and flavonoids and the intake from fruits was associated with lower GDM risk. This study was registered at clinicaltrials.gov as NCT03099837. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

AbstractThis study aimed to determine whether increased carotenoids intake was associated with reduced risk of gestational diabetes mellitus (GDM). We performed a cross-sectional analysis using data from Tongji Maternal and Child Health Cohort study. The dietary carotenoids intake of 1978 pregnant women was assessed using a researcher-administered FFQ before undertaking an oral glucose tolerance test at 24–28 weeks. Multivariate logistic and linear regression analyses were used to obtain the effect estimates. Participants in the highest quartile of lycopene intake showed a lower risk of GDM (OR 0·50; 95 % CI 0·29, 0·86;Pfor trend= 0·007) compared with those in the lowest quartile; each 1 mg increase in lycopene consumption was associated with a 5 % (95 % CI 0·91, 0·99;Pfor trend= 0·020) decrease in GDM risk. No significant association was found between α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin intake and GDM risk. Multiple linear regression analysis suggested an inverse association between lycopene intake and fasting blood glucose (FBG) (Pfor trend< 0·001); each 1 mg increase in lycopene intake was associated with 0·005 (95 % CI 0·002, 0·007;Pfor trend< 0·001) mmol/l decrease in FBG. Interaction analysis indicated consistent effect on each age or pre-BMI subgroup; however, a stronger protective effect of lycopene intake against GDM was observed among primigravid women (OR 0·20; 95 % CI 0·07, 0·55 in the highestv. the lowest quartile of intake;Pfor interaction= 0·036). In conclusion, dietary lycopene intake was mainly assumed via reducing FBG to decrease GDM risk, and the protection was relatively increased among primigravid women.

Objective To evaluate the effect of Annexin-A1 mimetic peptide Ac2-26 on activation of astrocytes in rats.Methods The primarily cultured astrocytes from the cortex of fetal Sprague-Dawley rats after 4 passages were divined into 4 groups (n =24 each) using a random number table method:control group (C group),LPS group,LPS+scramble peptide group (LPS+Src group) and LPS+Ac2-26 group.LPS was added to LPS group with the final concentration of 1 mg/ml.LPS at the final concentration of 1 mg/ml and scramble peptide at the final concentration of 3.3 mmol/L were added to LPS+Src group.LPS at the final concentration of 1 mg/ml and Ac2-26 at the final concentration of 3.3 mmol/L were added to LPS+Ac2-26 group.After 24-h incubation,the cell survival rate was measured by CCK-8 assay,the migration was determined by Transwell assay,the concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-1 beta (IL-1β),monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 a (MIP-1a) in the supernatant were measured (by enzyme-linked immunosorbent assay),and the expression of glial fibrillary acidic protein (GFAP),extracellular signal-regulated kinase (ERK),phosphorylated ERK (p-ERK),c-Jun N-terminal kinase (JNK),phosphorylated JNK (p-JNK),p38 mitogen-activated protein kinase (p38MAPK),and phosphorylated p38MAPK (p-p38MAPK) in astrocytes was detected by Western blot.Results Compared with group C,the expression of GFAP was significantly up-regulated,and the cell mobility,concentrations of TNF-α,IL-1β,MCP-1 and MIP-1α in the supernatant,p-ERK/ERK ratio,p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were increased (P＜0.05),and no siguificant change was found in the cell survival rate in group LPS (P＞0.05).Compared with group LPS,the expression of GFAP was significantly down-regulated,and the cell mobility,concentrations of TNF-α,IL-1β,MCP-1 and MIP-1α in the supernatant,p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were decreased in group LPS+Ac2-26 (P＜0.05),and no significant change was found in the parameters mentioned above in group LPS+Src (P＞0.05).Conclusion Ac2-26 can inhibit activation of astrocytes and produces anti-inflammatory effect in rats.

This study was to explore the link between gamma-glutamyl transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) levels during early-middle pregnancy and subsequent risk of gestational diabetes mellitus (GDM). In a prospective cohort study, pregnant women enrolled prior to 16 weeks of gestation were followed up until delivery. GGT, AST and ALT levels were tested during weeks 14-18 of gestation and oral glucose tolerance test was conducted during 24-28 weeks to screen GDM. The GDM rate was 8.1% (122/1512). Mean GGT level was higher in GDM than non-GDM women (18.7 ± 13.0 vs 14.5 ± 7.0, P < .001). The higher GGT level was 26.9~74.0 U/L, which was significantly associated with increased risk of GDM. The adjusted RR (95% CI) comparing higher GGT level versus lower was 5.40 (3.36-8.68). No significant correlation was found between ALT or AST levels and the risk of GDM. The results suggest that pregnant women with higher serum GGT during early-middle pregnancy have higher risk of developing GDM. A GGT level >26.9 U/L may indicate an increased risk of developing GDM later and should be further concerned.

SummaryObjectiveThis study was to explore the link between gamma‐glutamyl transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) levels during early‐middle pregnancy and subsequent risk of gestational diabetes mellitus (GDM).MethodsIn a prospective cohort study, pregnant women enrolled prior to 16 weeks of gestation were followed up until delivery. GGT, AST and ALT levels were tested during weeks 14‐18 of gestation and oral glucose tolerance test was conducted during 24‐28 weeks to screen GDM.ResultsThe GDM rate was 8.1% (122/1512). Mean GGT level was higher in GDM than non‐GDM women (18.7 ± 13.0 vs 14.5 ± 7.0, P < .001). The higher GGT level was 26.9~74.0 U/L, which was significantly associated with increased risk of GDM. The adjusted RR (95% CI) comparing higher GGT level versus lower was 5.40 (3.36‐8.68). No significant correlation was found between ALT or AST levels and the risk of GDM.ConclusionsThe results suggest that pregnant women with higher serum GGT during early‐middle pregnancy have higher risk of developing GDM. A GGT level >26.9 U/L may indicate an increased risk of developing GDM later and should be further concerned.

Objective: Hepatic stellate cells (HSCs) play essential roles in the development of liver fibrosis by increasing accumulation of extracellular matrix proteins in the damaged liver. We previously demonstrated that astaxanthin (ASTX) and lutein (LT) have antifibrogenic properties in LX-2, a human HSC cell line, when testing 5 carotenoids, ASTX, LT, lycopene, zeaxanthin, and canthaxanthin. The objective of this study was to determine the mechanisms of the antifibrogenic effect of ASTX and LT in HSCs. Methods: Primary HSCs isolated from C57BL/6J mice were cultured on uncoated plastic dishes for spontaneous activation in the presence or absence of 25 µ M of ASTX or LT to determine their effect on HSC activation. The cells were harvested at day 1 or day 7 for quiescent or activated HSCs, respectively, to measure the expression of fibrogenic genes. In addition, we determined whether the SMAD3 pathway mediates the antifibrogenic effect of ASTX and LT by measuring levels of phosphorylated SMAD3 and total SMAD3 in LX-2 cells stimulated by transforming growth factor β 1 in the presence or absence of ASTX and LT. Results: Activation of mouse primary HSCs was confirmed by drastic induction of fibrogenic genes, such as α -smooth muscle actin ( α -SMA), procollagen type I α 1 (Col1a1), Col3a1, Col6a1, andCol6a3,inactivatedHSCscomparedwithquiescentHSCs.Importantly,thepresenceofASTX during HSC activation significantly reduced mRNA levels of α -SMA, SMAD3 pathway were determined in LX-2 cells and human primary HSCs from quantitative real-time polymerase chain reaction and Western blot analysis. The modulatory roles of FCX in the activation of quiescent HSCs to activated HSCs were also evaluated in mouse primary HSCs isolated from C57BL/6J mice. Results: FCX exhibited cell viability of > 90% and > 75% at concentrations of 2.5 and 5 μ M, respectively. TGF β 1 increased the mRNA levels of profibrogenic genes, such as α -smooth muscle actin ( α -SMA) and procollagen type I α 1 (Col1A1), in LX-2 cells and human HSCs. However, FCX significantly inhibited the induction. As the SMAD3 pathway is known to mediate TGF β 1-induced fibrogenesis in HSCs, we determined whether FCX can regulate SMAD3 activation, i.e., phosphorylation, in LX-2 cells. TGF β 1 stimulated phosphorylation of SMAD3, which was markedly attenuated by FCX. When quiescent mouse primary cells were cultured on an uncoated plastic plate for activation for 4 d, mRNA levels of α -SMA, procollagen genes such as Col1a1, Col3a1, Col6a1, and Col6a3, and the tissue inhibitor metalloproteinase-1 were induced. However, the presence of FCX during the activation significantly reduced these mRNA levels. In addition, cells treated with FCX displayed more cytoplas-mic lipid droplets, a characteristic of quiescent HSCs, than control cells. Conclusion: The results suggest that FCX exerts antifibrogenic effects by preventing TGF β 1-induced profibrogenic gene expression, which it achieves by inhibiting SMAD3 activation in HSCs and by inhibiting the activation of quiescent HSCs. Background: We have previously reported that a high-refined-carbohydrate diet (HRCD) is more likely to contribute to nonalcoholic fatty liver disease (NAFLD) than is a high-fat diet with the same caloric content. The HRCD effect is associated with decreased functions of sirtuin 1 (SIRT1). β -Cryptoxanthin (BCX), a provitamin A carotenoid found primarily in red sweet peppers, has been shown to be protective against NAFLD. BCX can be cleaved by β -carotene-15,15 (cid:3) -oxygenase (BCO1), and β -carotene-9 (cid:3) ,10 (cid:3) -oxygenase (BCO2) to produce bioactive metabolites. BCO1/BCO2 polymorphisms have been observed in human and rodents. Objective: In this study, we investigated whether the protective effect of BCX against HRCD-induced NAFLD was dependent on, or independent of, BCO1/BCO2, and whether upregulation of SIRT1 was the mechanism underlying the physiologic actions of BCX. Methods: At 6 wk of age, BCO1/BCO2 double knockout (BCO1/BCO2 DKO) mice and wild-type (WT) from a C57BL/6J genetic background randomly to either the HRCD as carbohydrate including sucrose and maltodextrin) or the HRCD BCX and retinal and (IQ) among and and 7-d diet records were used to assess whole-body adiposity (%fat), and dietary lutein and zeaxanthin intake (LZ), respectively. Results: Initial bivariate correlations indicated that IQ was associated with %fat ( r = –0.25, P = 0.04) and positively with sex ( r = 0.30, P ≤ 0.01), MPOD ( r = 0.26, P = 0.03), TMV ( r = 0.23, P ≤ 0.05), RNFL volume ( r = 0.35, P ≤ 0.01), GCL volume ( r = 0.26, P = 0.03), and CFT ( r = 0.33, P ≤ 0.01). However, LZ intake was not significantly related to IQ ( r = 0.20, P = 0.16). Based on regression modeling, following adjustment for sex and %fat, only CFT ( β = 0.28, R 2 = 0.17, P = 0.03) and RNFL ( β = 0.33, R 2 = 0.20, P ≤ 0.01) were independent predictors of IQ. MPOD ( β = 0.21, R 2 = 0.14, P = 0.06)andGCL( β = 0.23, R 2 = 0.14, P = 0.06)approachedstatistical significance. Conclusions: Our data suggest that macular xanthophylls and retinal morphology are markers of intellectual ability in adults. Future work is necessary to continue bridging the gap in the literature relating retinal structural and pigmentation measures to cognitive health. reverse necrosis cytometry. Lycopene Conclusion: These results show that individual carotenoids can regulate M Ф scavenger receptor and cytokine expression. We speculate that dietary carotenoids influence TAM polarization, hence, that modulations in TAMs can greatly affect cancer progression and metastasis. Objective: Colorectal cancer (CRC), the third most common cancer worldwide, has high rates of recurrence and metastasis. These characteristics are ascribed to cancer stem cells (CSCs), i.e., the small population of cancer cells that possess characteristics of stem cells. β -Carotene (BC) has been reported to be effective at suppressing CSCs in neuroblastomas. The objective of this study was to analyze the anti-CSC effect of BC in colorectal cancer. Methods: We used clonogenic assays and sphere formation assays to measure the self-renewal capacity of CSCs. CSC markers and the Wnt/ β -catenin signaling pathway were analyzed in CD133 + CD44 + HCT116 and HT29 colon cancer cells, and in primary cells from human CRC tissues. The xenograft model was used to investigate the tumorigenicity of CSC in mice after 10 wk of BC supplementation. Result: CSCs were isolated after double staining of CD133 and CD44. BC reduced the number and size of colonies and spheres, indicating that BC hindered the self-renewal capacity of CSCs. BC also downregulated CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, and Sox2, and the Wnt/ β -catenin signaling pathway, including β -catenin in CD133 + CD44 + HCT116 and HT-29 cells. The anti-CSC effect of BC was confirmed in primary cells isolated from human CRCs. In addition, the number and size of tumors were decreased and the time of onset of tumor was delayed by BC supplementation in xenograft mice injected with CD133 + CD44 + HCT116 cells. BC also inhibited CSC markers and the Wnt/ β -catenin signaling pathway in tumors in vivo . Conclusions: BC exerted an inhibitory effect on colon CSCs by regulating cancer stemness, indicating its therapeutic potential for the treatment of CRC. Conclusion: Taken together, the present study provided novel experimental evidence that the ablation of both BCO1/BCO2 led to the development of NAFLD, indicating that BCO1/BCO2 could play a significant role in maintaining normal hepatic lipid and cholesterol homeostasis, potentially through the activation of the FXR/miR-34a/SIRT1 pathway. Background: Lung cancer and chronic obstructive pulmonary disease (COPD) are caused by cigarette smoke (CS). 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most potent carcinogen in CS. Epidemiologic studies suggest an inverse association between the consumption of lycopene, a major carotenoid naturally occurring in tomatoes and tomato products, and the risk of lung cancer. Objective: We hypothesize that lycopene protects against CS/NNK-induced COPD and preneoplastic lesions in the ferret lung. Methods: Ferrets, a nonrodent model that closely mimics human carotenoid accumulation and lung lesions, were randomly divided into four groups ( n = 12–16/group): control, NNK NNK + lycopene mg kg body wt d ) and NNK + high lycopene

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for ~80% of all lung cancer cases. The aim of the present study was to identify key genes and pathways in NSCLC, in order to improve understanding of the mechanism of lung cancer. The GSE33532 gene expression dataset, containing 20 normal and 80 NSCLC samples, was used. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to obtain the enrichment data of differently expressed genes (DEGs). Disease modules within NSCLC were constructed by Cytoscape, using protein-protein interaction (PPI) from the Search Tool for the Retrieval of Interacting Genes database. In addition, the Kaplan Meier plotter KMplot was used to assess the top hub genes in the PPI network. As a result, 1,795 genes were identified in NSCLC; 729 were upregulated and 1,066 were downregulated. The results of the GO analysis indicated that the upregulated DEGs were significantly enriched in 'biological processes' (BP), including 'cell cycle and nuclear division'; the downregulated DEGs were also significantly enriched in BP, including 'response to wounding', 'anatomical structure morphogenesis' and 'response to stimulus'. Upregulated DEGs were also enriched in 'cell cycle', 'DNA replication' and the 'tumor protein 53 signaling pathway', while the downregulated DEGs were also enriched in 'complement and coagulation cascades', 'malaria' and 'cell adhesion molecules'. The top 9 hub genes were cyclin-dependent kinase 9 (CDK1), polo-like kinase 1, aurora kinase B, cell division cycle 20, baculoviral initiator of apoptosis repeat containing 5, mitotic checkpoint serine/threonine kinase B, proliferating cell nuclear antigen (PCNA), centromere protein A and MAD2 mitotic arrest deficient-like 1, and the KMplot results revealed that the high expression levels of these genes resulted in significantly low survival rates, compared with low expression samples (P<0.05), with the exception of PCNA and CDK1. In the pathway crosstalk analysis, 26 nodes and 41 interactions were divided into two groups: One module of the two groups primarily included 'metabolism of amino acid' and the other primarily contained 'tumor necrosis signaling' pathways. In conclusion, the present study assisted in improving the understanding of the molecular mechanisms underlying NSCLC development, and the results may help the understanding of the biological mechanism of NSCLC.

Objective To study the relationship between serum 25-hydroxyvitamin and prediabetes.Methods Based on the diagnostic criteria of diabetes meatus of the ADA(2009),325 patients were selected as prediabetes group,and 203 healthy subjects were selected as control group.The biochemical parameters of human were measured and serum 25-hydroxyvitamin D [25(OH)D]was measured by enzyme linked immunoassay.Logistic regression analysis was used to analyze the relationship between prediabetes and its related factors.The odds ratios and 95%confidence interval of diabetes were calculated respectively according to quartiles of serum 25(OH)D.Results The total prevalence of predia-betes among more than 27 years old in Wuhan city was 18.3%.The levels of serum 25(OH)D in the prediabetes group and control group were(34.4±12.3)nmol/L and (43.5±18.4)nmol/L,and there were significant differences among two groups(P<0.01).Logistic analysis showed lower serum 25(OH)D level was a predictor of prediabetes[β=-0.31,OR=1.42,P=0.03].After adjusting for age,sex,BMI,blood pressure,TC,TG and HOMA-IR,the odds ratio of prediabetes was significantly Increased [OR=1.46,95%CI(1.15-1.86),P<0.05]when serum 25(OH)D levels were below23.5 nmol/L.Conclusion Lower serum 25(OH)D levels are associated with prediabetes,the decreased ser-um levels 25(OH)D increased onset risk of prediabetes.

Objective To explore the correlation between bilirubin concentrations and gestational diabetes mellitus (GDM) during mid-pregnancy.Methods The pregnant women were collected from the Central Hospital of Wuhan,Huazhong University of Science and Technology,the basic data were obtained through retrospective study.Vanadate oxidation method was used to test total bilirubin (TB) and direct bilirubin (DB),enzymatic method was used to test fasting GLU.Immune turbidimetry was used to test CRP and Alb.Results The morbidity of GDM was 7.86％ (102/1 297).The mean of total bilirubin and direct bilirubin in GDM were lower in non-GDM(5.8 ±2.2 and 6.4 ±2.4,P =0.023;2.4 ± 1.3 and 2.5 ±0.9,P =0.036).Two-piecewise linear regression analysis was further adopted to assess the correlation between total bilirubin、direct bilirubin and fasting glucose、1h blood glucose、2h blood glucose.In multiple logistic regression analysis,the relative risk (RR) of developing GDM was lower in the highest layer of the total bilirubin and direct bilirubin levels than that in the lowest layer (RR 0.54;95％ CI,0.31-0.95) and (RR 0.61;95％ CI,0.38-0.99).Conclusion The results suggested that pregnant women with higher serum bilirubin had lower risk for the development of GDM during mid-pregnancy.

Objective To investigate the role of OMA1 in acute kidney injury (AKI) induced by lipopolysaccharide (LPS).Methods OMA1 wild-type and knocked out mice (8 week old) were injected with 10 mg/kg body weight of LPS.The model was confirmed by testing mouse serum creatinine and blood urea nitrogen.The apoptosis in mouse kidney cortex was examined by TUNEL staining and cleaved caspase 3.In vitro,in humam kidney proximal tubular cells (HK2) were knocked down OMA1 by transfecting OMA1 shRNA,with the scramble shRNA being used as negative control of transfection.HK2 cells were cultured with 5 μg/ml of LPS for 24 hours to induce apoptosis.DAPI staining of cells and caspase-3 activity were applied to test apoptosis.The images of mitochondria in cells were obtained by transfection of mito-green plasmid and OMA1 shRNA.Western blotting was used to exam the OMA1 and Cytochrome C expressions.Resudts Compared with OMA1 KO mice,LPS induced more severe AKI of WT mice with higher Scr [(97.2±26.5) μmol/L vs (53.0±17.7) μmol/L,P ＜ 0.05] and BUN [(43.3± 13.7) mmol/L vs (29.7±7.7) mmol/L,P ＜ 0.05].Moreover,there were more apoptosis cells in kidney cortex in WT mice than in OMA1 KO mice [(75.4± 26.1)/ram2 vs (38.3± 14.4)/mm2,P＜ 0.05].About 46％ of OMA1 expressions in HK2 cells were inhibited by OMA1 shRNA transfection (P ＜ 0.05).Further,OMA1 shRNA cells with LPS stimulation had decreased mitochondria fragmentation [(29.8±10.9)％ vs (43.2±6.8)％,P ＜ 0.05],Cytochrome C release [(37.0±12.3)％ vs (76.0±26.2)％,P ＜ 0.05],and cell apoptosis [(13.2±3.9)％ vs (25.0±7.1)％,P ＜ 0.05] as compared with control cells.Conclusion Knockdown of OMA1 alleviated septic AKI through inhibition of cell apoptosis,mitochondria fragmentation,and Cytochrome C release.

Objective Objective To observe the effect of Annexin-A1 mimetic peptide Ac2-26 on microglia released tumor necrosis factor-a(TNF-a),interleukin-1 b(IL-1b),interleukin-6 (IL-6) and nitric oxide (NO),and to explore its impact on expression of Toll Like Receptor-2(TLR2).Methods Rat primary microglial cells were randomly divided into 4 groups by different treatments:Aβ1 42 group (stimulated by Aβ1-42),Aβ1-42 plus scramble control (co-stimulated by Aβ1-42 and scramble control),Aβ1 42 plus Ac2-26 (co-stimulated by Aβ1-42 and Ac2-26)and blank control group.After above treatments for 24 hour,the microglial cells were collected.Microglial cell viability was measured by CCK-8 assay kits.The inverted phase contrast microscope was applied to observe the morphological changes of microglia.The concentrations of TNF-a,IL-1β,IL-6 and NO in the supernatant were measured by commercial kits,and the level of TLR2 protein expression was detected by Western blot assay.Results The Aβ1-42 and Ac2-26 had no effect on the microglial cell viability.After activation with Aβ1-42,the microglia showed an obvious morphological change.The microglia cell soma showed obvious changes,from resting ramified state into the activated amoeboid macrophage-like appearance.The Aβ1-42 group,Aβ1-42 + scramble control group,Aβ1 42 + Ac2-26 group and blank control group showed that the supernatant levels of TNF-a were (125.17 ± 7.13),(118.78± 7.28),(24.02 ± 2.62),(20.89 ± 1.82)ng/L,respectively,the supernatant levels of IL-1β were (117.61±8.73),(108.90±6.53),(27.06±3.32),(24.58±3.45) ng/L,respectively,and the supernatant levels of IL-6 were(108.6 7± 5.86),(102.67 ± 4.85),(25.94 ± 2.83),(19.68 ± 2.66) ng/L,respectively.The supernatant levels of TNF-a,IL-1β and IL-6 were significantly lower in the Aβ1-42 + Ac2-26 group than in Aβ1-42 group and Aβ1-42 + scramble control groups,and had no significant difference compared with blank control group;and the supernatant level of NO showed the similar result as the above.The supernatant levels of NO were lower in Aβ1-42 + Ac2-26 group(20.27±2.53)mmol/L than in Aβ1-42 group (75.68±6.14)mmol/L and in Aβ1-42 +scramble control group(69.25±4.50)mmol/L,and had no statistical significance compared with blank control group (16.39± 2.96)m mol/L.The protein expression level of TLR2 was significantly downregulated in the Aβ1-42 +Ac2-26 group than in Aββ142 group and Aβ1-42 +scramble control group.However it showed no significant difference compared with blank control group.Conclusions Ac2-26 can effectively inhibit the released TNF-a,IL-1β,IL-6 and NO from microglia induced by Aβ1-42,mainly through downregulation TLR2.Ac2-26 may serve as a novel targeted drug for treatment of Alzheimer's Disease.

Objective To explore the association between serum gamma glutamyl transpeptidase (GGT) and fasting blood-glucose,evaluating the modification effects of body mass index (BMI),age,sex,and lipids.Methods The normal control group (120 cases),the hospitalized patients with three times of the average fasting blood glucose (6.0 ～7.0 mg/dl) (128 cases),and the hospitalized patients with three times of the average fasting blood glucose (＞7.0 mg/dl) (124 cases) were selected in this study.Immune turbidimetry was used to test the serum of GGT,aspartate aminotransferase (AST),alanine aminotransferase (ALT),alkaline phosphatase (ALP),total cholesterol (TC),and triglycerides (TG).Enzymatic method was used to test glucose (GLU).High performance liquid chromatography-electrospray mass spectrometry was used to measure glycosylated hemoglobin A1c (HbAlc) in the blood.Results (1) The value of GGT was significantly higher in the patients with type 2 diabetes,but the fasting blood glucose was above of 7.0 compared to the other two groups (P ＜ 0.05).(2) After adjustment of many confounders,the significance of the highest GGT quartile band compared to the lowest was obviously among three groups (P ＜ 0.05).Conclusions GGT is expected to predict the development of disease in the process of treatment of type 2 diabetes.

Objective To explore the effects of different severities of neuronal injury on microglial phenotype. Methods Primary neurons were treated by hypoxia for 0.5 ,1 ,2 ,and 4h,and then reoxygenated for 24 h.Neuron‐conditioned media (NCM)were collected and added to microglial cultures(1∶1 volume).Twenty‐four h later ,Western blot was used to detect the expressions of the microglial M 2 phenotype marker arginase‐1 and the activation marker ionized calcium binding adapter mole‐cule 1(Iba‐1).Immunofluorescence was performed to detect the expression of arginase‐1.Additionally ,microglial trophic mole‐cules brain‐derived neurotrophic factor(BDNF) ,glial cell line‐derived neurotrophic factor(GDNF)and proinflammatory cyto‐kines TNF‐α,IL‐1β,IL‐6 were determined by ELISA. Finally ,different phenotypes of primary microglia were formed after cells were treated with different NCM.MTT assays were used to determine the viability of neurons which were treated by hypoxia for 2 h and then co‐cultured with microglia for 24 h.Results NCM from mild injuries(treated by hypoxia for 0.5 or 1 h)signifi‐cantly down‐regulated the expression of the microglial M 2 phenotype marker arginase‐1 ,and those from moderate and severe in‐juries up‐regulated the arginase‐1 expression. Iba‐1 was upregulated in all injury conditions ,suggesting that all the injury condi‐tions can induce microglial activation to some degree.Moreover ,NCM from mild injuries up‐regulated the secretion of microglial TNF‐α,IL‐1βand IL‐6 ,but NCM from moderate(hypoxia 2 h)and severe(hypoxia 4 h)injuries had no effects on these proin‐flammatory cytokines. NCM of different injury severities significantly up‐regulated the release of these trophic molecules. MTT assays demonstrated that microglia incubated with NCM of mild and severe injuries further exacerbated the injury of neurons treated by hypoxia.Microglia incubated with NCM of moderate injuries protected neurons from hypoxia injury.Conclusion The severity of neuronal injury is an important factor in determining microglial phenotypes ,which has neurotoxic or neuroprotective effects.

目的：通过测定湖北地区0岁（小于1岁）健康儿童血清补体C3水平，观察其血清补体C3的分布情况。方法收集415例该院及儿童医院体检0岁健康儿童血清，应用美国贝克曼库尔特IM AGE800特定蛋白分析仪（免疫散射比浊法）测定其血清补体C3水平，并对结果进行统计分析。结果该地区健康0岁儿童血清补体C3水平男女间比较差异无统计学意义（ P＜0．05），其95％参考范围为0．57～1．60 g／L。结论当前临床沿用《全国临床检验操作规程》及厂家所给的成人补体C3正常参考范围不适用于本实验室0岁儿童，各实验室应根据自身情况制订正常参考范围。