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

Objective: To investigate the quality and influencing factors of direct drinking water in schools in Nanjing City, so as to provide basis for management of school drinking water. Methods: From April to July 2023, direct drinking water equipment from 146 primary and secondary schools were selected from Nanjing City using a stratified random sampling method and tested for colony forming units (CFU) and permanganate index. Mann-Whitney U test was used to compare the differences between groups, and multiple linear regression was used to analyze the influencing factors. Results: The CFU and permanganate levels of school direct drinking water in Nanjing City were 1.00(0.00,15.50)CFU/mL and 0.47(0.26, 0.75)mg/L, respectively. The CFU level increased when the filter replacement time exceeded 3 months and when the water source was piped, while the permanganate index increased when the filter replacement time exceeded 3 months and using activated carbon technology ( Z =-2.21, -3.92, -2.31, -8.45 , P <0.05). The results of multiple linear regression analysis showed that the replacement time of filter element exceeding 3 months was positively correlated with the CFU level, and the process type involving activated carbon, a laid pipe network and a filter replacement time exceeding 3 months were positively correlated with the permanganate index( β =167.08, 0.32, 0.35, 0.11, P ＜0.05). Conclusions There are certain problems with the water quality of primary and secondary school direct drinking water in Nanjing City. Schools should promptly replace the filter and maintain the drinking water equipment to ensure the hygiene and safety of campus water quality.

Objective: To systematically evaluate the willingness to receive influenza vaccines among Chinese medical staff, so as to provide the evidence for developing the influenza vaccination strategy and improving the coverage of influenza vaccination among medical staff. Methods: Publications pertaining to the willingness to receive influenza vaccines among Chinese medical staff were retrieved from international and national databases from January 1, 2010 to October 1, 2023, including CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science and Embase. A meta-analysis was performed using the software Stata 17.0, sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using Funnel plot. Results: Totally 674 publications were retrieved, and 17 case-control studies were finally enrolled, with 23 697 participants. Meta-analysis showed that the rate of willingness to receive influenza vaccines among medical staff in China was 52.8% (95%CI: 41.3%-64.4%). The rates of willingness to receive influenza vaccines were 40.2% (95%CI: 28.5%-51.8%) in 2019 and before and 67.2% (95%CI: 56.5%-77.9%) in 2020 and beyond; 54.6% (95%CI: 44.2%-65.0%) in men and 56.8% (95%CI: 49.3%-64.4%) in women; 53.6% (95%CI: 40.9%-66.2%) in doctors, 53.9% (95%CI: 41.0%-66.8%) in nurses, 62.8% (95%CI: 46.2%-79.3%) in technicians and 53.1% (95%CI: 36.1%-70.0%) in administrative and logistical staff; 77.4% (95%CI: 63.7%-91.2%) and 43.3% (95%CI: 30.5%-56.1%) in staff with and without a history of influenza vaccination; 49.8% (95%CI: 27.3%-72.3%) and 58.3% (95%CI: 43.9%-72.6%) in studies with a sample size of <1 000 and ≥1 000, and these differences were statistically significant (all P<0.05). Sensitivity analysis showed robustness of results, and Funnel plot showed publication bias. Conclusion The rates of willingness to receive influenza vaccines among medical staff in China ranged from 41.3% to 64.4%, and were lower in studies in 2019 and before, in men, in administrative and logistical staff and in staff without a history of influenza vaccination.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objective:To investigate the clinicopathological characteristics of oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG).Methods:Six cases of fundic gland-type tumors(three OGA and three GA-FG)diagnosed at the Fujian Cancer Hospital between August 2020 and February 2023 were retrospectively analyzed.The clinical data,endoscopic features,pathological charac-teristics,immunohistochemical results,treatment,and prognosis were analyzed.Results:Six patients with an average age of 57 years,in-cluding one male and five females,were mainly affected in the gastric fundus and body,with the superficial elevated type being the most common.The pathological features of gastric gland-type tumors are mostly located in the deep layer of the gastric mucosa,showing a dis-ordered glandular structure mainly composed of chief cell-type cells.There were three cases of OGA and three cases of GA-FG.Immunohis-tochemical results showed that pepsinogen 1 was positive in five cases,mucin 6(MUC6)in five cases,synaptophysin(Syn)in six cases,chro-mogranin(CgA)was negative in all cases,and Ki-67 was less than 10%.Conclusions:The incidences of OGA and GA-FG are low,and there is no obvious endoscopic specificity.Endoscopy physicians have an insufficient understanding,which can easily lead to misdiagnoses and missed diagnoses.Immunohistochemistry is helpful for the differential diagnosis,and endoscopic mucosal resection or stripping is the pre-ferred treatment option.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

Objective To investigate the efficacy and safety of Xihuang capsules as an adjuvant treatment for metastatic colorectal cancer and their impact on immune function. Methods A retrospective analysis was conducted on clinical data from 112 patients diagnosed with metastatic colorectal cancer. The patients were categorized into two groups: a control group (n=56) that did not take Xihuang capsules and an observation group (n=56) that did. The efficacy, improvement of quality of life, toxic and side effects and immune function of the two groups were analyzed and compared. Results After treatment, the disease control rate (DCR) and the rate of improvement in quality of life were significantly higher in the observation group compared to the control group. Additionally, levels of carcinoembryonic antigen (CEA) and the incidence of adverse reactions, including bone marrow suppression and liver and kidney function damage, were significantly lower in the observation group. Furthermore, the percentages of CD4⁺ and CD8⁺ T cells, the CD8⁺/CD4⁺ T cells ratio, as well as serum levels of high mobility group box-1 (HMGB1) and interleukin 2 (IL-2) in observation group were significantly elevated compared to pre-treatment levels. Subgroup analysis revealed that patients with a Karnofsky Performance Status (KPS) score ≤80, a high CD8⁺/CD4⁺ T cells ratio, and elevated HMGB1 levels experienced a significantly higher objective response rate (ORR) in the observation group. Conversely, patients with stage IVB disease, who had KPS score ≤80, a low CD8⁺/CD4⁺ T cells ratio and high CEA and IL-2 levels demonstrated a more pronounced DCR in the observation group. Conclusion Xihuang capsules exhibit promising clinical efficacy as an adjuvant treatment for advanced colorectal cancer. They not only enhance patients' quality of life and reduce the toxic and adverse effects of chemotherapy, but also improve immune function. These benefits are particularly significant in patients with a high tumor burden, indicating that Xihuang capsules are worthy of clinical application.
Humans ; Colorectal Neoplasms/immunology* ; Male ; Female ; Middle Aged ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Aged ; Carcinoembryonic Antigen/blood* ; Retrospective Studies ; Quality of Life ; Adult ; Neoplasm Metastasis ; Interleukin-2/blood* ; HMGB1 Protein/blood* ; Chemotherapy, Adjuvant

【Objective】 To analyze the SARS-CoV-2 detection results among blood donors in different periods of COVID-19 pandemic control in Shenzhen and assess the antibody levels and infection status of blood donors in different periods, so as to provide reference for subsequent blood testing strategies. 【Methods】 A total of 4 768 plasma samples of blood donors were subjected to pooled testing by nucleic acid testing(NAT) with 8 samples per pool. Additionally, these samples were subjected to a 1000-fold dilution, and the detection of SARS-CoV-2 total antibody was performed by enzyme-linked immunosorbent assay (ELISA). The 4 768 plasma samples were collected from blood donors at different time points in Shenzhen, with inquiries made to determine whether donors during the COVID-19 pandemic were in the convalescence. The antibody positive rates in blood screening samples during different periods of the pandemic and samples from individuals in the convalescence of COVID-19 infection were analyzed. Furthermore, the antibody levels were examined for differences based on gender, age, and blood type. 【Results】 All 4 768 plasma samples from blood donors were negative by NAT, while 2 342 samples were detected positive by the SARS-CoV-2 total antibody detection, with a positive rate of 49.1%. These samples from four periods (September 30 to October 3, 2022; November 3 to 6, 2022; December 27 to 31, 2022; January 6 to 18, 2023) were subjected to a 1 000-fold dilution for COVID-19 antibody detection, and the positive rates were 21.3%, 15.8%, 65.9%, and 93.9%, respectively. 【Conclusion】 The prevalence of COVID-19 antibodies among blood donors in Shenzhen during different periods of the pandemic varied significantly. There was no difference in antibody prevalence among different genders and blood types, while younger individuals exhibited a higher prevalence of antibodies. The risk of COVID-19 transmission through blood transfusion was found to be extremely low.

Background N-nitrosodimethylamine (NDMA), a new disinfection by-product in drinking water, has attracted extensive attention due to its high detection rate and concentration. Objective To investigate the concentration of NDMA in drinking water in Nanjing situated in the lower Yangtze River Basin of China, and to evaluate associated human health risk. Methods In dry period (January–March) and wet period (July–September) of 2021, raw water, finished water, and tap water from 16 centralized water treatment plants in Nanjing were collected to detect the concentration of NDMA in water samples by solid phase extraction and gas chromatography-triple quadrupole mass spectrometry with programmable temperature vaporizer-based large volume injection. The concentrations of NDMA in water samples of different water types, water periods, and disinfection methods were analyzed, and the daily exposure levels and carcinogenic risk values of NDMA in drinking water of different exposure routes and different exposed populations were calculated. Monte Carlo simulation was implemented with Crystal Ball 11 software to establish a health risk assessment model and conduct sensitivity analysis. Results A total of 61 drinking water samples were collected in Nanjing, and NDMA was positive in all the water samples, with concentrations ranging from 1.36 to 25.65 ng·L⁻¹ and an overall average concentration of (8.00±4.06) ng·L⁻¹. There were no statistically significant differences in the average concentrations of NDMA among raw water, finished water, and tap water samples (F=2.875, P=0.064), between wet season and dry season (t=−0.855, P=0.397), or among different disinfection methods by liquid chlorine, sodium hypochlorite, and chlorine dioxide (F=0.977, P=0.385). The results of health risk assessment showed that the average carcinogenic risk of NDMA and its P₉₅ were 5.95×10⁻⁶ and 1.12×10⁻⁵ respectively for oral intake of drinking water, and the values for dermal contact were both lower than 1.00×10⁻⁶. The mean carcinogenic risks of exposure to drinking water NDMA in children, adolescents, and adults were 1.84×10⁻⁶, 8.27×10⁻⁷, and 3.28×10⁻⁶, respectively. The results of sensitivity analysis showed that the contributions of daily drinking water volume and NDMA concentration in drinking water to the calculated health risk were high, and the contribution of body weight was negative. Conclusion There is a potential carcinogenic risk of NDMA in the drinking water of Nanjing section of the lower Yangtze River Basin，but it is within the acceptable range.

Objective To summarize the electrophysiological indexes and scales used for evaluation of post-stroke spasticity, for integration of clinical management of spasms. Methods Literatures on identification and evaluation of post-stroke spasticity from databases of Web of Science, PubMed, CNKI, and Wanfang Data up to May 15, 2021 were retrieved and the indicators related to post-stroke spasticity were extracted for a scoping review. Results The scales of modified Asworth Scale, Comprehensive Spasticity Scale and modified Tardieu Scale; the electrophysiological indexes of F wave, H reflex, motor evoked potentials, visual-startle reaction time and vestibular evoked myogenic potentials were used to identify and evaluate post-stroke spasticity. Conclusion More clinical researches are needed to explore earlier identification and evaluation of post-stroke spasticity more objectively and accurately.