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

Improving the evaluation mechanism for scientific and technological talents has become an important task for China's reform of the scientific and technological system.Under this context,this study aims to offer theoretical and practical ref-erences for improving evaluation mechanisms for scientific and technological talents in public hospitals.In this study,the current situation of the evaluation of scientific and technological talents in public hospitals was reviewed.Main existing problems were an-alyzed and advancements in the assessment were introduced.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients. METHODS: This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group. RESULTS: We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37-2.59, P  <0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29-3.85, P  = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51-2.03, P  = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58-4.78, P  = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period. CONCLUSIONS The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.
Humans ; Prospective Studies ; East Asian People ; Disease Progression ; Severity of Illness Index ; Pulmonary Disease, Chronic Obstructive/epidemiology*

OBJECTIVE: To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China. METHODS: From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells. RESULTS: Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153. CONCLUSION The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.
Male ; Humans ; East Asian People ; China ; Genotype ; Alleles ; Asthma/genetics* ; Serotonin Plasma Membrane Transport Proteins

Fecal microbiota transplantation (FMT) refers to using the intestinal microorganisms present in the feces or processed feces from healthy people for treating various types of diseases, such as digestive and metabolic diseases. The rapid development of metagenomic and culturomic technologies in gut microbiome analysis provides powerful tools for the FMT research and its clinical applications. Metagenomics technologies comprehensively revealed the diversity and functions of gut microbiota under health and disease conditions, while culturomics technologies helped isolation and identification of "unculturable" bacteria in the human gut under conventional culture conditions. The combination of these two technologies not only enabled us better understand the FMT regularities of cause and effect in clinical practices, but also effectively promoted its applications. Considering the above advantages, this article summarized the applications of metagenomics and culturomics technologies in FMT and prospected its future development trend.
Humans ; Fecal Microbiota Transplantation ; Metagenomics ; Feces/microbiology* ; Gastrointestinal Microbiome ; Bacteria

The rapid spread of carbapenemase-producing Klebsiella pneumoniae(cpKP)poses seri-ous threats to public health;however,the underlying genetic basis for its dissemination is still unknown.We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates col-lected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009-2017 by short-/long-read sequencing.The results showed that most cpKP isolates were categorized into clonal group 258(CG258),in which ST11 was the dominant clone.Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates.Additionally,carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates,and most blaKPC genes were located in five major incompatibility(Inc)groups of blaKPC-harboring plasmids.Importantly,three advantageous combinations of host-blaKPC-carrying plasmid(Clade 3.1+3.2-IncFⅡpHN7A8,Clade 3.1+3.2-IncFⅡpHN7A8:IncR,and Clade 3.3-IncFⅡpHN7A8:InCpA1763-KPC)were identified to confer cpKP isolates the advantages in both genotypes(strong correlation/coevolution)and phenotypes(resistance/growth/competition)to facilitate the nationwide spread of ST11/CG258 cpKP.Intriguingly,Bayesian skyline analysis illustrated that the three advanta-geous combinations might be directly associated with the strong population expansion during 2007-2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008.We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections.Thus,the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China,and much emphasis should be given to the close monitoring of advantageous cpKP-plasmid combinations.

【Objective】 To investigate the environmental pollution of blood collection and supply institutions by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and evaluate its application value. 【Methods】 Colonies of air from blood donation sites, skin puncture sites of blood donors, platelet storage boxes, platelet collection equipment, object surfaces of related experimental consumables and cuff surfaces of staff after disinfection were collected, and typical colonies after cultivation were selected for microbial identification by microbial mass spectrometry and then compared with bacteria results detected in blood components from May 2017 to May 2021. 【Results】 Aseptic growth, the number of colonies ≤4.0 CFU/ dish, and the number of colonies > 4.0 CFU/dish accounted for 21.20%, 62.20% and 16.60%, respectively. The qualified rate from high to low was platelet storage box, bacteria settling in the air of blood donation room after disinfection, platelet collection equipment, skin puncture site of blood donors after disinfection, the surface of platelet consumables and the surface of medical staff's overalls. After disinfection, the blood donors' skin puncture sites were compared with other collection sites, and the t values were 2.0371, 1.508, 2.109, 1.961 and 1.778, respectively, with no significant difference (P>0.05). Thirty cases of bacterial contamination of blood components were detected from May 2017 to May 2021, among which the detection rate of apheresis platelets was the highest, and the t values were 1.731 and 2.272, relative to the contamination frequency of erythrocytes and plasma bacteria (P>0.05), while the t value was 2.875, relative to concentrated platelets, with significant difference (P<0.05). 【Conclusion】 Bacterial contamination of blood components mostly come from air bacteria settling, blood donors' arms and skin after disinfection, and surfaces of related equipment and materials. Therefore, it is of clinical significance to conduct strict disinfection of working sites, establish disinfection monitoring methods and formulate disinfection hygiene standards in blood stations.

OBJECTIVES: Pulmonary alveolar proteinosis (PAP) is a rare disease with non-specific and various clinical manifestations, often leading to misdiagnosis. This study aims to raise the awareness of this disease via summarizing the clinical characteristics, diagnosis, and therapy of PAP. METHODS: We retrospectively analyzed clinical data of 25 hospitalized cases of PAP during 2008 and 2019 in the Department of Respiratory and Critical Care Medicine of the Second Xiangya Hospital of Central South University. RESULTS: Cough with unkown reason and dyspnea were common clinical manifastations of PAP. Five patients had a history of occupational inhalational exposure. Sixteen patients had typical image features including ground-glass opacification of alveolar spaces and thickening of the interlobular and intralobular septa, in typical shapes called crazy-paving and geographic pattern. Fourteen patients underwent pulmonary function tests, revealing a reduction in the diffusing capacity for carbon monoxide. The positive rate of transbronchial biopsy was 95%. Five patients received the whole lung lavage and the symptoms and imaging fcauters significantly relieved after five-years follow-up. CONCLUSIONS PAP is characterized by radiographic pattern and pathology. Transbronchial lung biopsy is effective to make diagnosis of PAP. The whole lung lavage remains a efficient therapy.
Biopsy ; Bronchoalveolar Lavage ; Cough ; Dyspnea ; Humans ; Pulmonary Alveolar Proteinosis/therapy* ; Retrospective Studies

【Objective】 To observe the effect of hydrogen peroxide atomization sterilizer using low concentration hydrogen peroxide disinfectant on the environment and object surface of physical examination area (hereinafter referred to as " physical examination area" ) in blood centers, so as to provide a simple method which is safe, efficient, easy to operate, harmless to human body and has no corrosive effect on equipment. 【Methods】 The physical examination area was disinfected with atomized hydrogen peroxide sterilizer, and the difference of colony number between air and surface before and after disinfection was compared to evaluate the disinfection effect. 【Results】 After disinfection, the hydrogen peroxide residue was detected for 25 times at 5 points, and the results were (0.7~1)ppm, with no statistical difference (P>0.05). 25 tests were carried out at 5 points, and the quartile of the test results was (0~2)CFU/ dish, and the qualified rate was 100%. The test results of bacteria before and after disinfection were statistically significant (P<0.05), which met the requirements of Class Ⅱ environment in Hygienic Standard for Hospital Disinfection(GB15982-2012). After disinfection, the quartile of surface colony detection results of workbench, blood donor seat, screen and door handle were (0~24.1)CFU/cm^2, (1.6~55.4)CFU/cm^2, (0~7.2)CFU/cm² and (0~4.8)CFU/cm^2, with the qualified rate at 80%, 48%, 100% and 100%, respectively, which were in accordance with the requirements of Class Ⅲenvironment in GB15982-2012. The number of colonies after disinfection at the above detection sites decreased significantly compared with that before disinfection (P<0.05). The surface contact plate pressing method and cotton swab smearing method were used to detect the number of colonies on the surface of sterilized work tables and blood donor seats, and the detection rate of the former was higher than that of the latter, with statistical significance (P<0.05). 【Conclusion】 After disinfection by hydrogen peroxide atomization sterilizer, the hydrogen peroxide residue met the requirements specified in the manual. The terminal disinfection effect of air in the physical examination area environment can meet the Class Ⅱ environmental requirements of GB15982-2012. However, the number of microorganisms on object surface after terminal disinfection was significantly lower than that before disinfection.

Both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSA) are common respiratory diseases. Both can exist at the same time, which is referred to as the " overlap syndrome (OS)". Epidemiological studies showed poorer outcomes with increased comorbidities and mortality, which indicated complicated interactions between COPD and OSA. Even though the underlying mechanisms of overlap syndrome have not yet well understood, the airway and systemic inflammation as well as oxidative stress induced by hypoxia played an essential role in the disease interactions and pathogeneses of comorbidities, mainly cardiovascular diseases. One other question is that how to treat the overlap syndrome. This paper summarizes the current research progress of the overlapping interaction and treatment.