ObjectiveTo investigate mutations in exons 19, 20 and 21 of epidermal growth factor receptor (EGFR) gene in elderly patients with non-small cell lung cancer (NSCLC). MethodsEGFR gene mutations in exons 19, 20 and 21 were detected by nested PCR amplification and DNA sequencing in 46 elderly patients with non-small cell lung cancer. The relationship between mutations and clinical characteristics of these patients was analyzed. ResultsEGFR gene mutations were found in 56.5% (26/46) patients and 41.3% (19/46)were non-silent mutations. Mutation of exon 19 was detected in 6 cases (13.0%), mutation of exon 20 in 13 cases(28.2%) and that of exon 21 in 14 cases (30.4%). Seven patients among them had double mutations and the rest only had a single mutation. The incidence of EGFR gene mutations was higher in non-smokers than in smokers(P＜ 0.01). Higher EGFR mutation rate in exon 19, 20 and 21 were found in patients with clinical benefit who were treated with tyrosine kinase inhibitor(TKl)(P＜0.05). There was no difference in EGFR mutation rate between 60～69 age group and 70～85 age group. ConclusionsThe data suggest that the characteristics of EGFR gene mutations in elderly patients with NSCLC is the same as in the general NSCLC patients. The forecast informations of TKI treatment can be obtained by gene detection in elderly NSCLC patients.

Objective To investigate the risk factors for mild cognitive impairment (MCI) in elderly people in Beijing.Methods Using multistage cluster random sampling,129 elderly people aged 60-80 years living around Dongzhimen communities were interviewed by mini-mental state examination (MMSE) and National Institute of Neurological and Communicative Diseases and Stroke/ Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for screening MCI and Alzheimer's disease (AD).Results Thirty-seven cases (28.7%) had amnestic MCI (aMCI),thirty-six cases (27.9%) had AD,and fifty-six cases (43.4%) were with normal cognitive state (NCS).The age was older in aMCI patients or AD patients than in NCS[(67.6±7.5)y vs.(62.5±7.9)y,(67.6±7.5)y vs.(62.5±7.9)y,both P<0.01],Andthe aMCI or AD patients had low level of education (P<0.05).The blood pressure was higher in the patients suffered from aMCI or AD than in people with NCS more or less (P<0.05).The prevalence of aMCI was related to the body mass index (BMI) (P<0.05),while that of AD had no significant relation with BMI (P>0.05).The prevalence of aMCI or AD was not significantly different between male and female or between different birth months.(all P>0.05).Conclusions The prevalence of aMCI increases with age,lower level of education,higher level of blood pressure and BMI,while it has no significant relations with gender or birth month.

Antiviral Agents ; Diabetic Retinopathy ; Drug Combinations ; Hepatitis C, Chronic ; Humans ; Interferon-alpha ; Polyethylene Glycols ; Recombinant Proteins ; Ribavirin

Objective:To investigate the relationship between VitD 3 concentration and glucose and insulin levels of OGTT in patients with CKD 3-5 stages.Methods: We included the patients with CKD 3 and 4 and 5 stages who fulfill the including standard.All patients were recorded the concentrations of [1,25 (OH):D3]concentration of glucose and insulin at fasting ,postprandial 1 h,2 h during OGTT and concentration of glycosylated hemoglobin level ,C peptide concentration.We performed the correlation analysis about [1,25 (OH):D3],glucose and insulin.Results: We totally included 91 patients with 3-5 stages CKD into our study.The D3 concentration of stage 3 were 160.9-261.3 mmol/L[(218.38±8.67)mmol/L] of stage 3,75.2-166.3 mmol/L[(117.01±4.72) mmol/L] of stage 4 and 11.8-96.5 mmol/L[(41.91±12.83)mmol/L] of stage 5 (P<0.05).The average concentrations of serum glucose at fasting,1 h after the meal and 2 h after the meal was(4.74±0.21)mmol/L,(8.31±0.43)mmol/L and(7.36±0.32)mmol/L in 3 stage and (4.92±0.25) mmol/L,(9.14±0.15) mmol/L and (9.14±0.39)mmol/L at 4 stage and (4.81±0.13)mmol/L, (10.72±0.41)mmol/L and (10.72±0.49)mmol/L at 5 stage (P<0.05).The average concentrations of insulin during OGTT at fasting,1 h after the meal and 2 h after the meal was (6.58±0.32) μU/L,(57.78±5.63)U/L and (42.77±8.45)U/L in 3 stage (6.03±0.53)U/L,(55.69±7.35)U/L and (62.52±5.39)U/L in 4 stage and (6.12±0.65)U/L,(62.82±9.73)U/L and (77.34± 8.62)U/L in 5 stage (P<0.05).Correlation analysis shows that the concentration of 1,25 (OH):D3 of different stages of patients with CKD and vitamin D 3 concentration and glucose tolerance test was found to be inversely associated with the insulin levels ( P<0.05 ) . Conclusion:There are obvious differences of concentration of vitamin D 3 between patients with 3-5 stages of chronic kidney disease (CKD).There also showed a negative correlation relationships between glucose and insulin levels ,and vitamin D3 concentration and glucose and insulin levels at OGTT of patients with 3-5 stages CKD.

Objective To identify the significance of neuropsychological single-item scales in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD).Methods A total of 676 elderly people living around Dongzhimen district in Beijing were recruited using multistage sampling method.Cognitive function was assessed by minimum mental state examination (MMSE)and other scales.MCI was diagnosed based on the criteria proposed by Petersen (1999),and AD was diagnosed based on the NINCDS-ADRDA.Subjects were divided into normal cognitive group (n=213 cases,31.5％),Alzheimer's disease (AD) group (n=167 cases,24.7％),amnestic mild cognitive impairment (aMCI) group (n=186 cases,27.5 ％) and non-AD dementia group (110 cases,16.3 ％).Results The MMSE scores in AD,aMCI and normal groups were 23.0 ± 5.9,25.9±2.6,8.1 ± 1.7,respectively.There were significant differences in MMSE scores between AD,aMCI and NC groups separately (all P＜0.01).Compared with MCI and NC group,th scores of time orientation,attention,calculation and immediate recall and delayed recall were significantly decreased in AD group (all P＜0.01).Comparing with normal group,the scores of attention and calculation were reduced in aMCI group (both P＜0.01).The delayed story recall (DSR) scores in AD,aMCI and NC groups were 15.7 ± 11.7,7.6 ± 4.9,26.5 ± 9.3,respectively.There were significant differences in mean DSR scores between AD,aMCI and NC groups separately (all P＜0.01).Compared with normal group,the clinical dementia rating (CDR) scores were higher and the mean clock drawing task (CDT)scores were lower in AD and aMCI groups (both P＜0.01).Conclusions Both neuropsychological assessment tools such as MMSE and single-item scales such as delayed story recall have the certain significance in the diagnosis of MCI and AD.

Objective To study the function of Fkbp51 in the heart and liver by analyzing the differential RNA expression profiles in the wild-type mice (WT) and Fkbp51 knockout (KO) mice, and to elucidate the role of Fkbp51 gene in metabolic pathways in the heart and liver.Methods Using the second generation of high-throughput gene sequencing technology, the mRNA expression profiles of heart and liver were sequenced in WT and Fkbp51 KO mice.The data of sequencing of heart tissues were analyzed by DEGseq, and the results of sequencing of liver tissues were analyzed by BRB-Array Tools.The differential genes of the heart and liver in the mice were screened respectively.Gene ontology (GO) analysis and KEGG pathway analysis were performed to analyze the differentially expressed genes using the online tool DAVID.In addition, the differential genes of the two organ tissues were analyzed by Venn diagram.The interaction network of proteins was analyzed using the STRING database.Results (1) The absence of Fkbp51 led to changes in mRNA expressions of heart-related signal pathways such as vascular smooth muscle contraction, chemokine, retinol, and MAPK signaling pathways.(2) The lack of Fkbp51 mostly induced changes in cholesterol synthesis and metabolism, lipid metabolism, redox and other related genes and pathways in the liver.(3) In the heart and liver, Fkbp51 deletionresult ed in four co-differential genes, among them, down-regulation of Rnaset2b, Hmga1 and Fkbp51, while Cyp2b10 was down-regulated in the heart but up-regulated in the liver.All these proteins may interact with HSP90 protein and participat in the metabolism of heart and liver tissues.Conclusions Fkbp51 is involved in different metabolic and gene expression regulation pathways of heart and liver, and the roles are both independent and interrelated.

Objective:To investigate clinical features, diagnosis and treatment of angioimmunoblastic T-cell lymphoma(AITL)in middle and old age patients.Methods:This was a retrospective study.A total of 33 middle-aged and elderly patients(a median age of 64 years, range 47~85 years)with AITL admitted to our hospital from May 2008 to March 2017, including 54.5% male(18 cases), were enrolled in this study.Clinical manifestations, pathology, imaging and survival data of patients were collected.The objective response rate(ORR)of patients with different therapeutic regimens was analyzed.The survival analysis was conducted by using the Kaplan-Meier method, the survival rate was analyzed by using the Log-rank method, and multivariate analysis was conducted by using the proportional hazards regression model.Results:The median overall survival(OS)was 26.0 months(8.5-43.5 months). The 1-year, 3-year and 5-year OS rate was 66.7%(22 cases), 45.5%(15 cases)and 24.2%(8 cases), respectively.The ORR of first-line chemotherapy with CHOP-like regimens(cyclophosphamide, doxorubicin, vincristine, prednisone)was 65.5%(19/29)and the incidence of serious adverse reactions was 64.5%(20/31). Single-factor chi-square testing showed that age ≥60 years, Barthel score ≥90, Eastern Cooperative Oncology Group performance status score(ECOG-PS)≥2, anemia, International prognostic index(IPI)score of 4~5, receiving chidamide treatment were influncing factors for the prognosis in middle-aged and elderly patients with AITL( χ2=5.103, 4.306, 6.004, 4.030, 6.348 and 4.080, P<0.05). Cox multivariate analysis showed that age ≥60 years and receiving chidamide treatment were independent prognostic factors affecting the 5-year survival rate of middle-aged and elderly AITL patients( OR=0.313 and 4.964, P<0.05). That the OS was better in the group receiving chidamide treatment than in the group without chidamide treatment( P<0.05). Conclusions:Clinical features of AITL are diverse and lack of specificity.Most patients present with advanced stage AITL at the initial diagnosis.The 5-year OS rate is low.AITL patients aged over 60 years have a poor prognosis.Chidamide can improve the OS rate.

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and long-term survival of patients with advanced non-small cell lung cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study.Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy.Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were analyzed.Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols(all P>0.05).After 2 cycles of chemotherapy,the percentage of CD4CD29lymphocytes was(16.87±5.28)% in progressive disease group,which was significantly lower than those in complete remission+partial remission group [(22.42±7.88)%,P=0.013] and stable disease group [(21.88±6.81)%,P=0.009].The median PFS was 7.07 months and median OS was 23.00 months.Cox multivariable regression analysis showed that the percentages of HLA-DR(HR:1.03,95%CI:1.01-1.05,P<0.001) and CDHLA-DRlymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with OS.Conclusions The rise of CD4CD29T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy.Higher percentage of HLA-DRand CD3HLA-DRlymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.

Objective To understand the elonal expansion and genetic diversity of Salmonella en-terica semtype Paratyphi A (SPA) and to construct a typing method to determine the epidemic clones of the isolates. Methods Antimicrobial susceptibility testing was performed with 3980 SPA isolates by the cen-trolled Kirby-Bauer disc diffusion technique on Muller-Hinton agar plates. A total of 15 SPA with nalidixie acid resistance for mutations in gyrA, gyrB, gyrC and gyrE genes within the quinolone-resistant determina-tion region (QRDR) were examined. Subtyping of 121 isolates of SPA from seven counties in Yuxi were studied using pulsed-field gel eleetrophoresis (PFGE) analysis following digestion of chromosomal DNA with restriction endanucleases Spe Ⅰ and Xba Ⅰ. PFGE patterns were analyzed by duster analysis. Results The nalidixic acid-susceptible isolates predominated in 1999 but was replaced by nalidixic acid -resistant (NAR) isolates after 2000. Amplification by PCR and sequencing of the genes with subsets of 15 NAR strains re-vealed that the resistance mechanisms had resulted from single point mutations in the gyrA gene. Spe Ⅰ and Xba Ⅰ digestion of 121 isolates gave five and four different PFGE patterns with the predominance of the Spe Ⅰ 01 and Spe Ⅰ 02 (or the Xba Ⅰ 01) epidemic patterns, respectively. Spe Ⅰ 01 and Spe Ⅰ 02 consisted of 37.2% and 57.9% of isolates, respectively, or Xba Ⅰ 01 consisted of 95.0% of isolates. Conclusion The incidence of resistance to nalidixic acid of the isolates increased during the study period. PFGE patterns Spe Ⅰ 01 and Spe Ⅰ 02 (or Xba Ⅰ 01), the main clones of the epidemics, are highly prevalent in Yuxi. PFGE with Spe Ⅰ and Xba Ⅰ is a useful technique to differentiate SPA.

This study was performed to explore the differential genes and functions of double-negative T cells in peripheral blood of patients with colorectal cancer.Two colorectal cancer patients and two healthy physical examiners were selected,and peripheral blood double-negative T cells were firstly sorted by flow cytometry,and then sequencing data were obtained using single cell full-length transcriptome(SMART-seq2)sequencing technology to screen differentially expressed genes.The screened differentially expressed genes were subjected to Gene Ontology Enrichment(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The STRING database was used to construct the protein interaction network and identify key genes by Cytoscape software;RT-qPCR was used to verify the differential expression genes in DNT cells.Compared with healthy subjects,there were 1 276 peripheral blood double-negative T-cell differential genes in colorectal cancer patients,including 141 up-regulated genes and 1 135 down-regulated genes.GO analysis showed that the differential genes were mainly involved in biological functions such as methylation,metabolic processes and transferase activity;KEGG pathway analysis showed that the differential genes were mainly involved in signaling pathways such as autophagy,P53 signaling pathway and phosphatidylinositol metabolism.The protein interaction network contains 1 154 nodes and 1 022 edges,in addition,10 hub genes were identified:PIK3C3,WIPI1,ATG101,PIK3R4,DDX10,RBM28,SDAD1,ATG16L1,UVRAG,ATG7.RT-qPCR validated 10 differentially expressed genes,of which 7 differentially expressed genes showed trends consistent with sequencing results,and 3 genes showed expression inconsistent with sequencing results.DNT cells may be involved in the development of colorectal cancer through methylation,P53 signaling pathway and autophagy,and at the same time,DNT cells may inhibit the development of colorectal cancer through the regulation of genes.This study provides a theoretical basis for further investigation of the function of DNT cells in malignant tumors.