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 (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.
Humans ; Pulmonary Disease, Chronic Obstructive ; Tuberculosis, Pulmonary/complications* ; Asthma ; Tomography, X-Ray Computed/methods* ; Lung

The clinical data of 4 patients with acute eosinophilic pneumonia (AEP) diagnosed in the Department of Respiratory and Critical Care Medicine, Peking University Third Hospital were retrospectively analyzed. All 4 patients were males, aged 28, 34, 43 and 68 years respectively. The main manifestations were fever, cough and dyspnea. Three cases had a history of smoking and 1 case had a history of ulcerative colitis. The proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was 85%, 93%, 41% and 50%, respectively. The proportion of eosinophils in peripheral blood was 53.3% (16.29×10 9/L), 25.1% (1.29×10 9/L), 4.8% (0.4×10 9/L) and 13.7% (1.55×10 9/L), respectively. Blood gas analysis (without supplemental oxygen) showed type I respiratory failure in 1 case, hypoxemia in 3 cases. The total IgE (normal range ≤ 100.0 KU/L) in peripheral blood of the 4 cases was>2 500.0 KU/L, 60.3 KU/L, 379.4 KU/L and 407.0 KU/L, respectively. HRCT showed diffuse distribution of lesions in both lungs, including ground glass opacity, patchy consolidation and centrilobular nodules. After diagnosis, all patients were treated with systemic glucocorticoids. Fever, cough and dyspnea, as well as the chest CT lesions were significantly improved after treatment. The patients were followed up for 29 months, 16 months, 18 months and 24 months respectively, without recurrence. AEP is a rare disease which is easy to be misdiagnosed as severe pneumonia and/or ARDS. Eosinophilia in peripheral blood is suggestive of the disease, and timely BALF cell differentials is important for early diagnosis.

Objective:To analyze the clinical characteristics and short-term prognosis of patients with acute asthmatic attack and comorbid bronchiectasis.Methods:The data of patients hospitalized for acute asthmatic attack in the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 1, 2012 to December 31, 2021 were retrospectively collected and analyzed. According to whether or not co-existing with bronchiectasis, all the patients were divided into asthmatic with bronchiectasis group and asthmatic without bronchiectasis group. Then the general conditions, comorbidities, pulmonary function test, grades of asthma severity, laboratory examination and in-hospital short-term prognosis of two groups were analyzed.Results:A total of 580 hospitalized patients with acute asthma attack were included, of which 132 cases (22.76%) were classified into asthmatic with bronchiectasis group and 448 cases (77.24%) were classified into asthmatic without bronchiectasis group. Co-existing with obsolete pulmonary tuberculosis and anxiety/depression in asthmatic with bronchiectasis group were more common than that in asthmatic without bronchiectasis group (13.64% vs 5.36%; 7.58% vs 2.68%) (both P<0.05). The pre-bronchodilator forced vital capacity (FVC) and its percentage to the predicted value (FVC%pred), forced expiratory volume in 1 second (FEV 1) and its percentage to the predicted value (FEV 1%pred), FEV 1/FVC and post-bronchodilator FEV 1 in asthmatic with bronchiectasis group were lower than those in the asthmatic without bronchiectasis group [2.44 (1.90, 3.01) vs 2.69 (2.10, 3.68) L, 1.55 (1.13, 2.00) vs 1.78 (1.25, 2.52) L, 70.14% (67.39%, 85.92%) vs 79.63% (70.00%, 89.52%), 70.00% (54.38%, 78.11%) vs 70.00% (61.47%, 85.00%), 61.57% (56.29%, 73.03%) vs 66.67% (60.00%, 75.00%), 1.72 (1.21, 2.18) vs 1.89 (1.37, 2.55) L] (all P<0.05). In previous year, the proportion of patients receiving hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group was higher than that in asthmatic without bronchiectasis group (15.15% vs 8.93%) ( P<0.05). The peak months of hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group were April, July and October, and the peak months in asthmatic without bronchiectasis group were April and September. The length of hospital stay was longer and the proportion of patients receiving invasive ventilation was higher in asthmatic with bronchiectasis group than those in asthmatic without bronchiectasis group [10.06 (7.62, 13.94) vs 9.95 (7.15, 13.76) d; 5.30% vs 2.01%] (both P<0.05). The risk factors for invasive mechanical ventilation in asthmatic patients with acute attack during hospitalization were co-existing with bronchiectasis, smoking, high level of partial pressure of carbon dioxide in arterial blood, serum creatinine and creatine kinase. Conclusion:Asthma patients with comorbid bronchiectasis have more frequent acute attack, a longer hospitalization due to acute asthmatic attack and a higher probability of invasive ventilation during hospitalization.

Objective:To explore the independent risk factors that predict 10-year mortality in patients with stable chronic obstructive pulmonary disease(COPD).Methods:The baseline data from a prospective cohort study were analyzed and long-term follow-up were performed. Patients with confirmed diagnosis of stable COPD were consecutively enrolled in the outpatient clinic from January 2010 to December 2010, and were followed up until December 31, 2020. Cox regression analysis was used to determine the independent risk factors for all-cause mortality and mortality from respiratory causes in stable COPD patients.Results:A total of 182 stable COPD patients were enrolled and followed up for a median of 89 months. The 10-year mortality was 51.1%(93/182), and 9 patients died within one year. The leading cause of death was respiratory disorder, followed by cardiovascular and cerebrovascular diseases. The risk factors independently associated with all-cause mortality included old age( HR=1.936,95% CI: 1.610~2.328, P<0.01), increased baseline COPD Assessment Test(CAT)( HR=1.331,95% CI: 1.049-1.689, P=0.02) and the increased CAT in one year( HR=1.314,95% CI: 1.197-1.420, P<0.01). The risk factors independently associated with respiratory cause mortality included increased baseline CAT( HR=1.719,95% CI: 1.026-2.880, P=0.04), emphysema index(LAA%)( HR=1.062,95% CI: 1.007-1.120, P=0.03), and one year inecreased CAT( HR=1.342,95% CI: 1.198-1.505, P<0.01)was a protective factor. Conclusions:Old age, baseline CAT, one year increased in CAT and LAA% were independent influencing factors for 10-year mortality of stable COPD patients.

Objective:To investigate the basic knowledge of chronic obstructive pulmonary disease (COPD) among physicians in primary hospitals (county and township hospitals) in Shanxi province.Methods:A electronic questionnaire survey that included questions on basic knowledge, epidemiology, diagnosis and management of COPD was conducted. The questionnaire was distributed through Wechat communication by convenient sampling among physicians and respiratory specialists in primary hospitals in Shanxi province.Results:A total of 1 162 questionnaires were collected, among which 1 100 were valid (882 from county hospitals and 218 from township hospitals). The results showed that 768 (69.8%) considered that smoking and biomass fuel exposure were the main risk factors of COPD, while 639 (58.1%) thought that COPD patients needed to quit smoking. Only 334 respondents (30.4%) indicated that their COPD knowledge was derived from guidelines; 764 respondents (69.5%) considered pulmonary function tests as the gold standard for diagnosing COPD, but only 407 (37.0%) provided correct answers for the specific criteria of pulmonary function, and only 98 respondents (8.9%) correctly identified the diagnostic criteria for severe COPD. In comparison with the county hospital group, fewer doctors in the township hospitals received their COPD knowledge from guidelines [23.9%(52/218) vs.32.0%(282/882), χ 2=5.450, P<0.05]; more doctors in the township hospitals experienced difficulties in the diagnosis and treatment of COPD, including inadequate spirometers in their hospitals [59.6%(130/218) vs. 45.2% (399/882), χ 2=14.509, P<0.01] and significantly inadequate COPD medications [42.7%(93/218) vs.34.2%(302/882), χ 2=5.385, P<0.05]. Significantly lower proportions of general physicians performed pulmonary function tests for COPD patients (χ 2=12.638, P<0.01) and provided correct answers for the diagnostic criteria for severe COPD [6.6%(46/692) vs. 12.7%(52/408), χ 2=11.760, P<0.01] in comparison with respiratory specialists. Conclusions:Doctors in primary hospitals in Shanxi have an inadequate knowledge of COPD. Strengthening COPD-related education and promoting the use of guidelines among doctors remain important issues for successful management of COPD.

Objective To investigate the target achievement of serum trough concentration of vancomycin in elderly patients routinely treated with vancomycin,and to analyze the influencing factors for vancomycin-associated acute kidney injury(VA-AKI).Methods A single-center retrospective study was conducted by collecting clinical data of elderly inpatients from January 2016 to July 2017 who received intravenous vancomycin therapy and serum vancomycin trough concentration test.Logistic regression was used to analyze the risk factors for VA-AKI.Results A total of 141 patients were enrolled,including 74 males (52.5 ％) and 67 females (47.5 ％).The median (interquartile range)age was 77.0(13.5) years old.Patients with serum vancomycin trough concentrations within 10～ 20 mg/L accounted for 48.9 ％ (69 cases),while those lower than the target value accounted for 23.4 ％ (33 cases),and those higher than the target value accounted for 27.7％ (39 cases).Patients were divided into three groups according to the vancomycin serum trough concentration:＜10 mg/L group,10～20 mg/L group,and ＞20 mg/L group.There were statistically significant differences among the three groups in median(interquartile range) age[74.0 (14.0) years old,76.0 (11.5) years old vs.80.0 (14.0) years old,H =9.506,P =0.009] and the median (interquartile range) vancomycin daily dose [1.5(0.5) g/d,1.5 (0.8) g/d vs.1.5 (0.5) g/d,H =6.131,P =0.047].VA-AKI occurred in 23 patients(16.3 ％).Logistic regression analysis showed that the baseline serum creatinine levels (OR =1.022,95 ％CI:1.001 ～ 1.042,P =0.035)and vancomycin trough concentration(OR =1.058,95 ％CI:1.011～1.106,P=0.015)were influencing factors for VA-AKI.Conclusions The elderly patients with infection who received clinical vancomycin therapy have a low target achievement rate of serum trough concentration.Baseline serum creatinine level and serum vancomycin trough concentration are influencing factors for VA-AKI.

PURPOSE: Chronic cough in allergic rhinitis (AR) patients is common with multiple etiologies including cough variant asthma (CVA), non-asthmatic eosinophilic bronchitis (NAEB), gastroesophageal reflux-related cough (GERC), and upper airway cough syndrome (UACS). Practical indicators that distinguish these categories are lacking. We aimed to explore the diagnostic value of the fraction of exhaled nitric oxide (FeNO) and forced expiratory flow at 25% and 75% of pulmonary volume (FEF(25–75)) in specifically identifying CVA and NAEB in these patients. METHODS: Consecutive AR patients with chronic cough were screened and underwent induced sputum, FeNO, nasal nitric oxide, spirometry, and methacholine bronchial provocation testing. All patients also completed gastroesophageal reflux disease questionnaires. RESULTS: Among 1,680 AR patients, 324 (19.3%) were identified with chronic cough, of whom 316 (97.5%) underwent etiology analyses. Overall, 87 (27.5%) patients had chronic cough caused by NAEB, 78 (24.7%) by CVA, 16 (5.1%) by GERC, and 81 (25.6%) by UACS. Patients with either NAEB or CVA (n = 165, in total) were further assigned to a common group designated as CVA/NAEB, because they both responded to corticosteroid therapy. Receiver operating characteristic curves of FeNO revealed obvious differences among CVA, NAEB, and CVA/NAEB (area under the curve = 0.855, 0.699, and 0.923, respectively). The cutoff values of FeNO at 43.5 and 32.5 ppb were shown to best differentiate CVA and CVA/NAEB, respectively. FEF(25–75) was significantly lower in patients with CVA than in those with other causes. A FEF(25–75) value of 74.6% showed good sensitivity and specificity for identifying patients with CVA. CONCLUSIONS: NAEB, CVA, and UACS are common causes of chronic cough in patients with AR. FeNO can first be used to discriminate patients with CVA/NAEB, then FEF(25–75) (or combined with FeNO) can further discriminate patients with CVA from those with CVA/NAEB.
Asthma ; Bronchial Provocation Tests ; Bronchitis ; Cough ; Eosinophils ; Gastroesophageal Reflux ; Humans ; Methacholine Chloride ; Nitric Oxide ; Rhinitis, Allergic ; ROC Curve ; Sensitivity and Specificity ; Spirometry ; Sputum