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

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective: To investigate the trends in incidence of viral hepatitis in Yuxi City, Yunnan Province from 2004 to 2022, so as to provide insights into the management of viral hepatitis. Methods: Data of viral hepatitis cases in Yuxi City from 2004 to 2022 were retrieved from the China Disease Prevention and Control Information System. The temporal, human and spatial distribution of viral hepatitis cases were analyzed using a descriptive epidemiological method, and the trends in incidence of viral hepatitis were evaluated in Yuxi City from 2004 to 2022 using annual percent change (APC) and average APC (AAPC). Results: A total of 37 430 viral hepatitis cases were reported in Yuxi City from 2004 to 2022, with an average annual incidence rate of 91.27/105, and the incidence showed a tendency towards a rise (AAPC=12.686, P<0.05). There were 29 229 cases with hepatitis B, 5 796 cases with hepatitis C, 1 451 cases with hepatitis A, 520 cases with hepatitis E and 434 cases with unclassified hepatitis reported in Yuxi City, with average annual incidence rates of 71.27/105, 14.13/105, 3.54/105, 1.27/105 and 1.06/105, respectively. The average annual incidence rates of viral hepatitis were 98.24/105 and 78.94/105 among men and women, which both appeared a tendency towards a rise (AAPC=12.415% and 12.581%, both P<0.05). The highest average annual incidence of viral hepatitis was seen among residents at age of 25 to 29 years (139.89/105), with the lowest seen among residents at ages of 0 to 4 years (11.38/105), and the average annual incidence of viral hepatitis appeared a tendency towards a rise with age (P<0.05). The highest average annual incidence of viral hepatitis was seen in Huaning County (234.24/105), with the lowest seen in Chengjiang City (26.11/105), and the average annual incidence appeared a tendency towards a rise in Xinping County from 2004 to 2022 (AAPC=21.451%, P<0.05). Conclusions The reported incidence of viral hepatitis appeared a tendency towards a rise in Yuxi City from 2004 to 2022, with hepatitis B as the main type. High incidence was seen among men and adolescents. The viral hepatitis control strategy requires to be adjusted with adaptations to high-incidence hepatitis subgroups, residents and regions.

Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.

Abstract: Objective　To understand the epidemiological characteristics of the migratory bird population with hypertension in Hainan and to provide a basis for the health management of the migratory bird population. Methods　One hundred and eighty migratory birds with hypertension who had lived in in the Mangrove Bay community of Chengmai, Hainan for 3 months or more were selected as the study population. Demographic data, including gender, age, ethnicity, occupation, medication use, family history of hypertension, hometown living environment, Hainan living environment (presence of water area and greenbelt around the residence, type of water area and greenbelt), smoking and alcohol consumption, and height and weight were collected by questionnaire and physical examination to investigate the epidemiological characteristics of the study subjects, and unconditional dichotomous logistic regression analysis was used to identify factors affecting the reduction of blood pressure among the hypertensive migratory bird population before and after taking medication in Hainan. Results　A total of 180 study subjects were included, including 77 (42.8%) males and 103 (57.2%) females, with 78 (43.3%) subjects aged ≤65. The hypertension levels were: 87 (48.3%) had normal high blood pressure, 56 (31.1%) had grade 1 hypertension and 37 (20.6%) had grade 2 hypertension. The higher the blood pressure classification, the lower the percentage of migratory individuals whose blood pressure dropped during their stay in Hainan. Age, hypertension classification, dietary habits, living environment, body mass index (BMI), and alcohol consumption were associated with a decrease in blood pressure during Hainan among the study participants who took hypertension medication regularly. Salty diet (OR=2.778, 95%CI:1.070-7.213, P=0.036) and alcohol consumption (OR=2.686, 95%CI:1.042-6.925, P=0.041) were unfavorable factors for lower diastolic blood pressure before taking medication; overweight (OR=3.487, 95%CI:1.306-9.310, P=0.013) was an unfavorable factor in the reduction of diastolic blood pressure after taking medication. Conclusion　The blood pressure reduction is more significant in migratory individuals in migratory individuals under 65 years old, with a light diet, no alcohol consumption and normal BMI. Environmental factors, age, dietary habits and lifestyle are the main causes of blood pressure, which can provide a reference basis for the health management of the migratory birds with hypertension in Hainan.

Objective    To investigate the safety and efficiency of robotic lung segmentectomy. Methods    The clinical data of 110 patients receiving robotic or thoracoscopic segmentectomy in our hospital between June 2015 and June 2019 were retrospectively analyzed. The patients were divided into a robotic group [n=50, 13 males and 37 females aged 53.0 (46.0, 60.0) years] and a thoracoscopic group [n=60, 21 males and 39 females aged 61.0 (53.0, 67.0) years]. A propensity score-matched analysis was adopted to compare the perioperative data between the two groups. Results    After the propensity score-matched analysis, 34 patients were included in each group. In comparison with the thoracoscopic group, patients in the robotic group had less blood loss [40.0 (20.0, 50.0) mL vs. 60.0 (40.0, 80.0) mL, P<0.001], more stations of lymph node dissection [7.0 (6.0, 8.0) vs. 4.0 (3.0, 6.0), P<0.001], larger number of lymph node dissection [15.0 (11.0, 21.0) vs. 10.0 (6.0, 14.0), P=0.002], and a higher total cost of hospitalization [97.0 (92.0, 103.0) thousand yuan vs. 54.0 (42.0, 59.0) thousand yuan, P<0.001]. Conclusion    In contrast with the thoracoscopic segmentectomy, robotic segmentectomy has a similar operative safety, but less blood loss and a thorough lymphadenectomy.

Objective To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital,Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results Totally ,28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1％(2/22) cases. Catheter displacement occurred in 18％(4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21(95％,21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62％(13/21)newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81％(17/21). The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.

[Summary] Adrenocortical carcinoma is a rare disease with poor prognosis, and its pathogenesis is mainly related to genetic mutations, abnormal expressions of steroidogenic factor-1, insulin-like growth factor 2,cell growth factors including vascular endothelial growth factor, dysfunction of Wnt pathway, as well as dysregulation of microRNA and DNA methylation. In recent years, the intensive molecular studies provide a brand-new methodology to distinguish adrenocortical carcinomas from benign tumors in early stage.

Objective To explore a new mode of prenatal diagnosis and counseling for congenital heart disease (CHD) by interdisciplinary cooperation and the value of Grading scale of fetal echocardiography in disease management.Methods The Grading scale of fetal echocardiography and a new integrative service mode of prenatal diagnosis and counseling for CHD with multidisciplinary team,including obstetric sonographers,obstetricians,pediatric cardiologists and geneticists,was established.For pregnant women referred to prenatal clinic in Shanghai First Maternity and Infant Hospital from January 1,2011 to December 31,2012,counseling about the diagnosis,severity,treatment options and long-term prognosis would be provided based on detailed fetal echocardiography and the grading scales.The significance of such mode in the prenatal management of CHD was analyzed and the rate of pregnancy termination was compared by Fisher exact test.Result According to the Grading scale of fetal echocardiography,there were four categories:Class Ⅰ,minor anomalies probably without treatment requried; Class Ⅱ,simple defects with normal life quality following after-born therapy; Class Ⅲ,complex anomalies with reasonable life quality after treatment; Class Ⅳ,severe malformation requiring multiple stage surgical repair or with very poor prognosis.There were a total of 54 pregnancies confirmed to have fetal cardiac anomalies by echocardiography,among which 27 were terminated.The average age of pregnant women was (29±3) years old,the average gestational week was 28.0±3.8.The abortion rate in women with the fetuses diagnosed as Class Ⅳ CHD was 17/19,higher than that in Class Ⅰ,Ⅱ and Ⅲ (3/15,3/10 and 4/10,Fisher exact test,all P＜0.01).In 19 Class Ⅳ cases,only two twin pregnant women continued their pregnancies because the other fetuses were healthy.Abortion was conducted in all 7 fetuses associated with extra-cardiac,chromosome anomaly or genetic syndrome.Conclusion The establishment of new integrated mode of prenatal diagnosis and counseling for CHD and Grading scale of fetal echocardiography in a multidisciplinary manner could provide comprehensive and authentic information and ethical advices for the families.

Objective To investigate the value of the senile degenerative aortic valve calcification (AVC) and to analyze the correlative risk factors by color Doppler echocardiograph.Methods Aortic valves of 110 cases with AVC (study group) and 110 cases without AVC (control group) were observed by color Doppler echocardiograph.All the patients with AVC have been excluded of congenital and other acquired valves' diseases.The aortic valve' s shape and the diameters of aortic root were measured.At the same time,the peak systolic and diastolic velocities of aorta were detected.The different features were compared between the two groups.Results Test results showed significant differences in study group:Anteroposterior diameter of aortic annulus and the area of aortic valve were decreased by calcification; The anteroposterior diameter of aortic sinus increased and aorta transvalvular pressure gradient augmented; Detection rate of atherosclerosis (AS) of aorta and the peripheral artery stenosis of the study group were higher than that of control group; The AS increased pulse pressure and aggravated AVC; Correlative risk factors,in addition to age,included hypertension,hypercholesterolemia,osteoporosis,and so on.The correct diagnosis of the correlated diseases were on the basis of clinical examines.The rate of AVC with multi-factor was higher than that with single-factor.In addition,gender difference and the diameters of ascending aortic showed no significant difference in two groups.Relationship between diabetes of correlative factors and the rate of AVC showed no significant difference in two groups.Conclusion Morphologic abnormality and malfunction of aortic valve and the large artery in elder patients were caused by senile degenerative AVC.The more correlative risk factors,the worse showed.