ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.

ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction， and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups： sham-operated group， model group， Qingxin Jieyu granules low-， medium-， and high-dose groups （1.3， 2.6， 5.2 g·kg^-1）， and sacubitril valsartan sodium group （0.03 g·kg^-1）， with 10 mice per group. Except for the sham-operated group， all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters， including end-diastolic and end-systolic diameters （LVIDd， LVIDs）， diastolic and systolic posterior wall thickness （LVPWd， LVPWs）， end-diastolic and end-systolic volumes （LV Vold， LV Vols）， left ventricular ejection fraction （LVEF）， and fractional shortening （LVFS）. Additionally， the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify brain natriuretic peptide （BNP）， creatine kinase isoenzyme （CK-MB）， angiotensinⅡ （AngⅡ）， and lactate dehydrogenase （LDH） levels in the serum of mice. Histological analysis using hematoxylin-eosin （HE） and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors， including basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF）. Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase （p-AMPK） and phosphorylated mammalian target of rapamycin （p-mTOR） proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group， the model group mice exhibited significantly elevated levels of LV Vold， LV Vols， LVIDd， LVIDs， cardiac mass index， heart weight/tibia length ratio， BNP， LDH， and p-mTOR protein expression （P<0.05）， along with decreased levels of LVPWd， LVPWs， LVEF， LVFS， and p-AMPK protein expression （P<0.05）. The model group also displayed substantial inflammatory cell infiltration， collagen deposition in myocardial cells， reduced expression of bFGF and VEGF， mitochondrial swelling， and cristae fragmentation. Compared to the model group， the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs， LV Vold， LV Vols， BNP， CK-MB， LDH， and p-mTOR protein expression （P<0.05）， coupled with increases in LVEF， LVFS， and p-AMPK expression （P<0.05）. Improvements were observed across all treatment groups， including reduced inflammatory cell infiltration and collagen deposition， increased bFGF and VEGF expression， alleviated mitochondrial swelling， and the presence of autophagosomes and lysosomes. ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance， by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction， and down-regulating the p-mTOR expression.

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 explore the clinical effect of Busshenqiangji decoction combined with adalimumab(Adam)in patients with ankylosing spondylitis.Methods A total of 114 patients with ankylosing spondylitis were included and randomly divided into the Adam group and the combined group,with 57 cases in each group.Patients in the Adam group were given adalimumab by subcutaneous injection,40mg/time,once every other week.Patients in the combined group were treated with Bushenqiangji decoction(1 dose/day)on the basis of the above,and both groups were treated continuously for 12 weeks.The efficacy,Traditional Chinese Medicine(TCM)syndrome score,spinal function,clinical index,serological index and adverse reactions were evaluated between the two groups.Results The total effective rate was 92.98%(53/57)in the combination group,which was higher than that of the Adam group(75.44%,43/57,P＜0.05).After treatment,the total score of TCM syndromes,Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)and Bath Andylosing Spondylitis Function Index(BASFI)scores were decreased in the combination group,and which were lower than those of the adalimumab group(P＜0.05).After treatment,the finger-to-floor distance and occipital bone-to-wall distance were decreased in the combination group,and which were smaller than those in the Adam group(P＜0.05).The chest range of motion increased,and which was greater than that in the Adam group(P＜0.05).After treatment,serum levels of sclerostin and 25 hydroxyvitamin D were significantly increased in the combination group than those in the Adam group(P＜0.05).There were no significant differences in the total incidence rates of adverse reactions,such as skin rash and gastrointestinal reactions between the two groups[10.53%(6/57)vs.14.04%(8/57),P＞0.05].Conclusion Bushenqiangji decoction combined with adalimumab can play a synergistic role in the treatment of patients with ankylosing spondylitis,significantly improving the symptoms of pain and morning stiffness.The mechanism of action may be related to improving the expression of osteosclerosis protein and the increase of 25-hydroxyvitamin D.

Objective To explore the clinical effect of Busshenqiangji decoction combined with adalimumab(Adam)in patients with ankylosing spondylitis.Methods A total of 114 patients with ankylosing spondylitis were included and randomly divided into the Adam group and the combined group,with 57 cases in each group.Patients in the Adam group were given adalimumab by subcutaneous injection,40mg/time,once every other week.Patients in the combined group were treated with Bushenqiangji decoction(1 dose/day)on the basis of the above,and both groups were treated continuously for 12 weeks.The efficacy,Traditional Chinese Medicine(TCM)syndrome score,spinal function,clinical index,serological index and adverse reactions were evaluated between the two groups.Results The total effective rate was 92.98%(53/57)in the combination group,which was higher than that of the Adam group(75.44%,43/57,P＜0.05).After treatment,the total score of TCM syndromes,Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)and Bath Andylosing Spondylitis Function Index(BASFI)scores were decreased in the combination group,and which were lower than those of the adalimumab group(P＜0.05).After treatment,the finger-to-floor distance and occipital bone-to-wall distance were decreased in the combination group,and which were smaller than those in the Adam group(P＜0.05).The chest range of motion increased,and which was greater than that in the Adam group(P＜0.05).After treatment,serum levels of sclerostin and 25 hydroxyvitamin D were significantly increased in the combination group than those in the Adam group(P＜0.05).There were no significant differences in the total incidence rates of adverse reactions,such as skin rash and gastrointestinal reactions between the two groups[10.53%(6/57)vs.14.04%(8/57),P＞0.05].Conclusion Bushenqiangji decoction combined with adalimumab can play a synergistic role in the treatment of patients with ankylosing spondylitis,significantly improving the symptoms of pain and morning stiffness.The mechanism of action may be related to improving the expression of osteosclerosis protein and the increase of 25-hydroxyvitamin D.

Objective:To evaluate the effect of propofol on doxorubicin-induced cardiotoxicity in rats.Methods:Thirty SPF healthy male Sprague-Dawley rats, aged 2-3 months, weighing 200-220 g, were divided into 3 groups ( n=10 each) by the random number table method: control group (C group), doxorubicin group (D group) and propofol group (P group). The rat cardiotoxicity model was prepared by intraperitoneal injection of doxorubicin 2.5 mg/kg, and the administered dose was adjusted according to the daily body weight once every other day for a total of 6 times in D and P groups. Propofol 50 mg/kg was intraperitoneally injected after successful preparation of the cardiotoxicity model in P group. Blood samples were taken from the heart of the anesthetized rats at 2 h after propofol injection for determination of the concentrations of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) by enzyme-linked immunosorbent assay. Then the rats were sacrificed, and the myocardial tissues were obtained for microscopic examination of the pathological changes (with a light microscope) and for determination of the mitochondrial volume fraction, surface-area density, surface-area-to-volume ratio, mean mitochondrial area and the number density (by transmission electron microscopy). Results:Compared with C group, the concentrations of cTnI and CK-MB were significantly increased, and the mitochondrial volume fraction, surface-area density, and the number density were decreased in D and P groups ( P<0.05). Compared with D group, the concentrations of cTnI and CK-MB were significantly decreased, and the mitochondrial volume fraction, surface-area density, and the number density were increased in P group ( P<0.05). There was no significant difference in the surface-area-to-volume ratio and mean mitochondrial area among the 3 groups ( P>0.05). Conclusions:Propofol can attenuate doxorubicin-induced myocardial toxicity in rats.

OBJECTIVE To analyze the chemical components that were the absorbed in blood and liver tissue of rats after intragastric administration of aqueous extract from Abrus cantoniensis， and to speculate its possible metabolic pathways， providing reference for basic analysis of pharmacological substance in A. cantoniensis. METHODS Male SD rats were randomly divided into A. cantoniensis group （0.63 g/kg， calculated by crude drug） and blank group； they were given relevant drug solution/ultrapure water intragastrically. After a single dose， plasma and liver samples of rats in each group were collected. UPLC-Q-TOF/MS technology was used to identify chemical components that were absorbed in the blood and liver tissue of rats. RESULTS Totally， 30 chemical constituents were identified from the water extracts of A. cantoniensis， including alkaloids， flavonoids， organic acids， iridoids （such as L-abrine， schaftoside， isoshaftoside）. Ten prototype components and nine metabolites （such as decarboxylation and sulfation metabolites of protocatechuic acid， reduced sulfated metabolites of p-hydroxybenzoic acid） were identified from plasma samples； six prototype components and five metabolites （such as sulfated metabolites of p-hydroxybenzoic acid， decarboxylation and sulfation metabolites of p-hydroxybenzoic acid） were identified from liver samples. The main metabolic pathways included hydroxylation， demethylation， methylation， sulfation， glucuronidation， etc. CONCLUSIONS Alkaloids， flavonoids and organic acids are the main components of the aqueous extract from A. cantoniensis that are absorbed into the blood and liver， their metabolism mainly involves hydroxylation，demethylation， and sulfation.

Abstract Spinal curvatures has emerged as the third major chronic condition seriously threatening the physical and mental health of Chinese children and adolescents, with significant regional differences. Its etiology is complex and diverse, and early prevention and treatment are feasible, whereas treatment in later stages entails considerable difficulty and economic burden. Currently, the prevention and control of student spinal curvatures has been elevated to a national health strategy. A series of policy documents have been successively issued, and it has greatly facilitated the institutionalization and normalization of national routine screening for student spinal curvatures. However, it is still inadequate considering current prevention and control system for spinal curvatures in children and adolescents. There is an urgent need to establish a closed loop model based on China s institutional advantages, comprising Initial Screening-Diagnosis-Treatment-Preventive Control-Followup Assessment, to strengthen the safeguarding of spinal health in children and adolescents.

Objective: To analyze the prevalence of comorbidity of spinal curvature abnormality and malnutrition among primary and secondary school students aged 10-18 years in Tianjin in 2023, so as to provide scientific basis for the combined prevention of common diseases and multiple diseases among students and the construction of school health system. Methods: In September to October 2023, 31 884 primary and secondary school students aged 10 to 18 years in Tianjin were selected using stratified cluster random sampling. Abnormal spinal curvature in children and adolescents was assessed by Sereening of Spinal Curvature Abnormality of Children and Adolescents, while stunting, wasting, overweight, and obesity were determined according to the Screening for Malnutrition among Schoolage Children and Adolescents and Screening for Overweight and Obesity among Schoolage Children and Adolescents. The χ2 test was used to compare betweengroup differences in coprevalence, and multiple Logistic regression models were used to analyze the risk of different comorbidity types in different clusters. Results: The coprevalence of spinal curvature abnormality and malnutrition among primary and secondary school students in Tianjin was 1.6%, which was higher for girls than boys (1.8%, 1.4%), higher (2.5%) for senior high schools than for junior high schools and elementary schools (2.0%, 0.5%), and higher in rural than in urban areas (2.1%, 1.1%) (χ2=9.45, 141.92, 46.94, P<0.05). Multiple Logistic regression models showed that junior high school girls had a higher risk of incorrect posture comorbid with stunting and wasting (OR=4.52, 95%CI=1.84-11.06) and incorrect posture comorbid with overweight and obesity (OR=2.67, 95%CI=1.74-4.10) than boys, and that scoliosis/sagittal spinal abnormality comorbid with stunting and wasting (OR=0.10, 95%CI=0.02-0.44) risk was lower than that of boys, senior high school girls had a lower risk of scoliosis/sagittal spinal abnormality comorbid with overweight and obesity (OR=0.27, 95%CI=0.11-0.66) (P<0.05). Conclusions The coprevalence of spinal curvature abnormality and malnutrition is specific among primary and secondary school students in Tianjin, and the comorbidity type varies by gender and education stage. There is a need to increase prevention and control of spinal curvature abnormalities in school health working, intensive screening of key populations, and timely intervention.