Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Objective:To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).Methods:The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing(WES)and Sanger method were used for variant analysis and verification.Results:Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c. 307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T(p.Arg2319Leu) and c. 3145A>T(p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+ PP1+ PM2, PM2+ PM6+ PP2+ PP3, PM2+ PM5+ PM6+ PP2+ PP3 and PM2+ PM6+ PP2+ PP3), the remaining 14 cases of IHH patients had negative genetic screening. Conclusion:CHD7 gene variants may be related to IHH disease.

Objective:To explore the effect of combined orbicularis muscle double stitch operated on blepharoplasty.Methods:A total of 90 patients, 79 females and 11 males, aged 18-49 years, were treated by using combined orbicularis muscle double stitch procedure, that is, to fix upper lifting muscle, to remove partial fat, and to perform blepharoplasty.Results:All 90 cases＇ incisions were healed at the first phase, no obvious swelling and bleeding. Within 3-24 months follow up, all patients＇ upper eyelids were significantly improved. The skin was smoothy when closing eyes, and eyelash was up when opening eyes, and arc was natural and satisfactory.Conclusions:This method can improve the shape of the upper eyelid swelling and get long-lasting and stable physiological eyelid.

To investigate the association between red blood cell volume distribution width (RDW) and osteophytes.
 Methods: This cross-sectional study was conducted in the Department of Health Examination Center of Xiangya Hospital, Central South University in Changsha, Hunan Province, China. A total of 8 334 subjects were included in this study. The severity of osteophytes was graded using the criteria of the Osteoarthritis Research Society International (OARSI). Osteophytes incident was defined as at least one side of the knee had a osteophytes grade ≥1. According to the quartiles of the RDW level, the subjects were divided into 4 groups. Multivariate logistic regression analysis was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of the knee osteophytes incidence between each RDW group and the lowest level group. Tests for linear trends were conducted based on logistic regression using a median variable of RDW level in each category.
 Results: Quartile 1 (Q1), RDW≤9.78; Q2, 9.7813.10. The multivariable adjusted ORs (95%CI) of the prevalence of osteophytes were 1.38 (1.06 to 1.79) in the second percentile interval, and 1.27 (0.97 to 1.66) and 1.50 (1.15 to 1.94) in the third and fourth percentile interval, respectively. Test for linear trends suggested that there was a positive association between the RDW level and the risk of knee osteophytes incidence (P=0.019).
 Conclusion: The risk of osteophytes incidence increases with the increasing RDW levels.
China ; Confidence Intervals ; Cross-Sectional Studies ; Erythrocyte Volume ; Humans ; Incidence ; Odds Ratio ; Osteophyte ; blood ; epidemiology ; Risk Factors ; Severity of Illness Index

Objective To explore the correlations between self-management and quality of life in elderly patients with chronic heart failure (CHF) in Xinjiang Uygur Autonomous Region, so as to provide effective measures to improve quality of life of them. Methods A total of 750 elderly patients with CHF were selected as the research subjects by convenience sampling method from 5 regions of Xinjiang Uygur Autonomous Region from February to August 2015. General Data Questionnaire, Heart Failure Self-Management Scale and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were applied in the investigation to analyze the correlation between self-management and quality of life. Results A total of 750 questionnaires were distributed and 704 valid questionnaires were collected, with an effective recovery rate of 94.1%. The total score of self-management and MLHFQ in the 704 CHF patients was (47.6±11.1) and (57.1±18.5) respectively. Pearson correlation analysis showed that patients' self-management was positively correlated with quality of life (r=0.114, P＜ 0.05). Conclusions The overall level of self-management and quality of life in elderly patients with chronic heart failure in Xinjiang Region is mid-to-low. Nursing intervention can give full play to the initiative of self-management behavior in accordance with patients' cultural background, so as to improve their quality of life.

Objective To evaluate the significance of electronic gastroscopy examination combined with miR-21 in the diagnosis of gastric carcinoma.Methods 96 gastroscopy cases in Guangzhou General Hospital of Guangzhou Military Command were adopted from June,2011 to December,2012.The patients received gastric endoscopy examination,and the diseased tissue samples were taken out at the same time.To calculate the diagnosis rate and missed rate with gastroscopy,by comparing the gastroscopy diagnosis with the pathology diagnosis.To evaluate the expression level of miR-21 of the tissue by applying quantitative real time PCR.Results The diagnosis rates of gastric cancer,gastric ulcer,chronic superficial gastritis,gastroesophageal reflux gastritis,chronic atrophic gastritis under gastroscopy were 28.12 ％ (27/96),30.21％ (29/96),18.75 ％ (18/96),10.42 ％ (10/96),12.50 ％ (12/96).The diagnosis rate of gastric cancer was 100.00 ％ and the missed diagnosis rate was 6.90 ％ (2/29),the relative transcript level of miR-21 in the gastric cancer group was 54.41±6.66,which was obviously higher than the gastric ulcer group and the other groups (P ＜ 0.01).Conclusions Electronic gastroscopy is a clinically practical examination method in screening gastric cancer cases,evaluating the expression level of miR-21 in the diseased tissue under gastroscopy can enhance the accuracy of screening gastric cancer.Combining the two methods is useful in the diagnosis of gastric cancer.

Objective To investigate the effects of silencing STMN1 by siRNA on the sensitivity of oesophageal cancer cells Eca-109 to paclitaxel .Methods The STMN1 siRNA(siSTMN1) or scramble siRNA(SCR) were transient transfected into Eca-109 cells .The mRNA and protein levels of STMN1 were detected by qPCR and Western blot in the Eca-109 cells of different groups .In vitro paclitaxel sensitivity of siSTMN1 and SCR transfected Eca-109 cell lines was tested by MTT assay and colony formation as-say .Hoechst 33258 nuclear staining were used to investigate the effect of silencing STMN 1 on the sensitivity of SCR ,siSTMN1 transfected Eca-109 cells and nontreated counterparts under paclitaxel induced apoptosis .Results The transient transfection cell lines were successfully established .Both protein and mRNA levels of STMN1 were effectively down-regulated in the siSTMN1 transfected Eca-109 cells .Down-regulation of STMN1 significantly enhanced the sensitivity of Eca-109 cells in response to paclitaxel (P<0 .01) .In addition ,the siSTMN1 transfected Eca-109 cells displayed significant apoptosis as assessed by Hoechst nuclear stai-ning(P<0 .01) .Conclusion Silencing STMN1 by siRNA could enhance the sensitivity of oesophageal cancer cells Eca-109 to paclitaxel .

Objective To evaluate the influence of the single and multiple intervertebral space radiofrequency ablation nucleoplasty on the sheep cervical spine stability.Methods Twenty healthy adult sheep were randomly divided into single intervertebral space operation group (A group )and multiple intervertebral space operation group ( B group ),each group was subdivided into postoperative 24 hours group ( A1,B1 group ) and post- operative 3 months group ( A2,B2 group),each group had five sheep.Radiofrequency ablation nucleoplasty on sheep C3/4 in the single intervertebral space operation group or C3/4,C4/5 in multiple intervertebral space operation group.Preoperative cervical vertebrae roentgenograms from all samples in neutral,lateral,hyperextension and hyperflexion positions were collected,and 5F pipe was used as the survey mark of ieonography.For the postoperative 24 hours group( A1,B1 group ),the roentgenograms were collected postoperatively 24 hours later,while for post- operative 3 months group (A2,B2 group),they were collected postoperatively 3 months later.The height of operative intervertebral space,horizontal and angular displacement of neighboring vertebral body were measured respectively.Results The roentgenograms showed no any obvious decrease in the height of intervertebral disc and no any increase in horizontal and angular displacement of neighboring vertebral body were observed in single intervertebral space operation group (A group) and multiple intervertebral space operation group (B group ).There was no significant difference between pre - operation and post - operation in them ( P ＞ 0.05 ).Conclusions The stability of the sheep cervical spine had not been affected by the single or multiple intervertebral space radiofrequency ablation nucleoplasty on the basis of X-ray results.The radiofrequency ablation nucleoplasty had no influences on the stability of sheep cervical vertebrae.

Objective To evaluate the clinical effects of early endoscopic therapy for elderly patients with acute severe biliary pancreatitis.Methods Ninety-two elderly patients with acute severe biliary pancreatitis were randomly divided into 2 groups:ERCP group ( n =43) and non-ERCP group ( n =49).Serum TNF-a,IL-6,IL-8,the recovery time of blood amylase,the duration of abdominal pain,hospitalization,mortality and complications were compared.Results ERCP group showed a greater decrease in serum TNF-α,IL-6 and IL-8 levels than the control group ( 45.16 ± 13.48 ) μg/L v.s.( 176.89 ± 47.35 ) μg/L,(31.76 ± 13.85)μg/L v.s.(68.48 ±24.87) μg/L,(113.39 ±63.78) μg/L v.s.(309.86 ± 117.13)μg/L) (P ＜0.05 ).The duration of abdominal pain,the recovery time of blood amylase and hospitalization in ERCP group were significantly shorter compared to the non-ERCP group [ ( 10.2 ± 1.7 ) d v.s.( 13.2 ±2.4)d,(3.3 ±1.0)dv.s.(5.5 ±1.2)d,(15 ±1.6)dv.s.(20±3.0)d] (P＜0.05),and complication rate of the ERCP group was lower,too (5％ v.s.22％,P ＜ 0.05).Conclusion Early ERCP is safe and highly effective for the elderly patients with acute severe biliary pancreatitis.