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

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective:To evaluate the preventive effect of an antimicrobial peptide spray on chemoradiotherapy-induced oral mu-cositis in patients with hematologic malignancies.Methods:From December 2021 to July 2023,a total of 191 newly diagnosed pa-tients with hematologic malignancies undergoing concurrent chemoradiotherapy at our hospital were included in the study.Patients were divided into a treatment group(n=124,received antimicrobial peptide spray)and a control group(n=67,received placebo spray).All patients underwent standardized chemoradiotherapy regimens and oral care.Outcomes compared between groups includ-ed the incidence and severity of oral mucositis,ulcer healing time,pain scores,antibiotic usage,inflammatory markers[C-reactive protein(CRP),procalcitonin(PCT)],duration of neutropenia,adverse events,and quality of life.Results:The incidence of oral mucositis in the treatment group was significantly lower than in the control group(12.90％vs.31.34％,P＜0.05),with a relative risk reduction(RRR)of 58.84％,absolute risk reduction(ARR)of 18.44％,and a number needed to treat(NNT)of 5.423.The treatment group showed shorter ulcer healing time,lower pain scores,reduced antibiotic usage and intensity,lower mean levels of CRP and PCT,and a shorter duration of neutropenia.The incidence of exacerbated local pain and drug-related adverse reactions was also significantly lower in the treatment group,compared to the control group(P＜0.05),with no evident systemic toxicity ob-served.Patients in the treatment group reported higher quality of life and satisfaction scores(both P＜0.05).Conclusion:The an-timicrobial peptide spray effectively reduces the incidence and severity of chemoradiotherapy-associated oral mucositis,mitigates in-flammation and infection risk,and improves quality of life.

Objective:To evaluate the preventive effect of an antimicrobial peptide spray on chemoradiotherapy-induced oral mu-cositis in patients with hematologic malignancies.Methods:From December 2021 to July 2023,a total of 191 newly diagnosed pa-tients with hematologic malignancies undergoing concurrent chemoradiotherapy at our hospital were included in the study.Patients were divided into a treatment group(n=124,received antimicrobial peptide spray)and a control group(n=67,received placebo spray).All patients underwent standardized chemoradiotherapy regimens and oral care.Outcomes compared between groups includ-ed the incidence and severity of oral mucositis,ulcer healing time,pain scores,antibiotic usage,inflammatory markers[C-reactive protein(CRP),procalcitonin(PCT)],duration of neutropenia,adverse events,and quality of life.Results:The incidence of oral mucositis in the treatment group was significantly lower than in the control group(12.90％vs.31.34％,P＜0.05),with a relative risk reduction(RRR)of 58.84％,absolute risk reduction(ARR)of 18.44％,and a number needed to treat(NNT)of 5.423.The treatment group showed shorter ulcer healing time,lower pain scores,reduced antibiotic usage and intensity,lower mean levels of CRP and PCT,and a shorter duration of neutropenia.The incidence of exacerbated local pain and drug-related adverse reactions was also significantly lower in the treatment group,compared to the control group(P＜0.05),with no evident systemic toxicity ob-served.Patients in the treatment group reported higher quality of life and satisfaction scores(both P＜0.05).Conclusion:The an-timicrobial peptide spray effectively reduces the incidence and severity of chemoradiotherapy-associated oral mucositis,mitigates in-flammation and infection risk,and improves quality of life.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

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.

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 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.

Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder characterized by the development of hamartomas in the brain, heart, skin, kidney, lung, retina, and so on. One fetus from family 1 had a cardiac rhabdomyoma from 21 weeks and 6 days of gestational age, and developed multiple rhabdomyomas and tubers in the brain at 23 weeks and 5 days. The counter monozygotic twin fetus remained negative throughout the pregnancy according to imaging examination. A nonsense mutation in TSC2 (c.4762C>T, p.Gln1588*) was identified in both twins, but not in the mother. Family 2 was one pair of twin fetuses caused by a microdeletion of exon 30 within TSC2 inherited from their apparently asymptomatic mother with mosaic status. The larger fetus was identified as having the first cardiac rhabdomyoma from 17 weeks and 4 days of gestational age. The smaller fetus developed multiple rhabdomyomas until 25 weeks and 6 days of gestational age. Both families terminated the pregnancy. Here, we provide intrauterine examples of clinical variability among monozygotic twins suffering from TSC.