Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae(CRKP)limit clinical treatment options,and its virulence genes severely affect patient prognosis.This study aims to investigate the distribution of virulence genes,capsular serotypes,and molecular epidemiological characteristics of CRKP in ICU,to understand the characteristics of CRKP infections in ICU,and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU. Methods:A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed.Whole-genome sequencing was used to analyze the distribution of resistance genes,virulence genes,and capsular serotypes of the strains.The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae(KPN)multilocus sequence typing(MLST)database to determine the sequence types(STs)of the strains. Results:The age of the 40 ICU CRKP-infected patients was(69.03±17.82)years old,with various underlying diseases,and there were 20 patients with improved clinical outcome and 20 patients with death.The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid.Whole-genome sequencing results revealed that the strains predominantly carried blaKPC-1(29 strains,72.5%)and blaNDM-1(6 strains,15.0%),with 5 strains carrying both blaKPC-1 and blaNDM-1.Various virulence genes were detected,among which the carriage rates of genes such as entA,entB,entE,entS,fepA,fepC,fepG,yag/ecp,and ompA reached 100%,while the carriage rates of genes such as entD,fimB,iroB,iroD,fes,and pla were low.The CRKP strains isolated from ICU were predominantly ST11(27 cases,67.5%),with KL64 being the main capsular serotype(29 cases,72.5%).A total of 23 ST11-KL64 CRKP strains were detected,accounting for 57.5%. Conclusion:The main type of ICU CRKP is ST11-KL64,carrying various virulence genes,primarily those related to iron absorption.Furthermore,blaKPC has shifted from blaKPC-2 to blaKPC-1.Therefore,close monitoring of the molecular epidemiological changes of CRKP is necessary,and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.

Abstract By reviewing the advocacy framework and implementation path of global adolescent health promotion, summarizing the main health problems of adolescents worldwide and current status of adolescent health care services in China, an ecological model of adolescent health care was concluded according to the demands of adolescents towards health care services. A comprehensive intervention strategy, ie. multi sector cooperation, community participation and integration of hospital, school, community and family, etc, has been put forward to promote the health and sustainable development of adolescents.

Objective To investigate the current situation of quality of care for people with disabilities and the related factors. Methods In November, 2015, 399 disabled persons from five special service institutions in Hubei, China were conveniently sampled, and investigated with the Chinese version of Quality of Care and Support (QOCS) for people with disability scale and demographic questionnaire. Results The total score of QOCS was (38.11±6.24), and the proportion of total score in the dimensions of caring provision, caring environment and caring information were more than 70%. The score of QOCS was various with the age, domicile, employment, medical insurance, monthly household expenditure and expenditure for food of the people with disabilities, and the age (β=0.06, P<0.01) and medical insurance (β=-0.850, P<0.001) were the independent factors related with the score of QOCS. Conclusion People with disabilities self-reportedly satis-fied in the quality of care in Hubei, and it can be improved from the increase of medical insurance level.

Objective To investigate the quality of life, quality of care and support and social integration in persons with severe disabilities, and to analyze the relationship of quality of life with quality of care and support and social integration. Methods From September, 2015 to March, 2016, 399 persons with severe disabilities in Wuhan, China were investigated with World Health Organization Quality of Life-Disability Scale, World Health Organization Quality of Care and Support Scale-Disability Scale and Social integration Scale. Results The quality of life was in middle level in persons with severe disabilities, and positively correlated with the scores of quality of care and support (r> 0.11, P<0.05) and social integration (r>0.39, P<0.01). Conclusion The quality of life is related with the quality of care and support and social integration in persons with severe disabilities. Policy and support system should be targeted on it for the social security and rehabilitation.

Objective To compare echocardiographic parameters of left ventricular function in mice under anaesthesia with those in conscious condition.Methods Forty mice were randomized to anesthetic group and nonanesthetic group,all mice were examined in conscious state at baseline,then anesthetic group had intraperitoneal injection of ketamine and xylazine,the non-anesthetic group received intraperitoneal injection of the same volume of saline.Echocardiography was performed every 10min and every 15min after 30min time point until 60min.ResultsAnesthetic agent strikingly brought down heart function of mice.The nadir of heart rate,fractional shortening(FS),cardiac output(CO) occurred during 10-20min period and could not be restored to normal value at baseline even after 60min.Left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD) increased to maximum at 20min point,then decreased to value at baseline until 60min.LVEDD could be restored to baseline value while LVESD remained larger than baseline at 60min.Coefficient of variation of echocardiographic measurement in non-anesthetic group was smaller than those in anethetic group.FS and heart rate of all mice were highly corrrelated by regression analysis(r=(0.884),P