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 To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

Objective To systematically evaluate the effect of exercise therapy on body structure,function,and activity and partici-pation in patients with chronic nonspecific neck pain(CNSNP)based on the International Classification of Func-tioning,Disability and Health(ICF)framework. Methods A PICO framework was constructed,and randomized controlled trials(RCTs)on the intervention of different types of exercise therapy for patients with CNSNP were retrieved from databases of CBM,Wanfang data,VIP,CNKI,Cochrane Library,Embase,PubMed and Web of Science,from the establishment to March,2024.The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database(PEDro)scale,and the evidence quality of the outcome indicators was evaluated using GRADE.Data were syn-thesized and analyzed using RevMan 5.3,and the risk of bias was evaluated using Stata 18.0. Results A total of eleven RCTs involving 668 subjects were included.The scores of PEDro scale were five to eight.The types of interventions included muscle strength training,stability training,proprioception training,Yoga and Pi-lates.The control groups received placebo,physical factor therapy and health education.Exercise therapy could increase the craniovertebral angle(SMD=0.84,95%CI 0.42 to 1.26,P<0.001),reduce the Visual Analogue Scale score(SMD=-2.05,95%CI-2.58 to-1.52,P<0.001),increase the pressure pain threshold(MD=112.27,95%CI 75.03 to 149.50,P<0.001),increase the range of motion of cervical forward(SMD=1.24,95%CI 0.34 to 2.15,P=0.007)and lateral(SMD=1.52,95%CI 0.40 to 2.65,P=0.008)flexion,and improve the endurance of the deep cervical flexors(SMD=1.02,95%CI 0.10 to 1.94,P=0.03)and position sense of the cervical spine(SMD=-1.00,95%CI-1.47 to-0.53,P<0.001);however,it was not significant in improving the range of motion of backward flexion(SMD=0.85,95%CI-1.04 to 2.75,P=0.38)and rotation(SMD=1.65,95%CI-0.35 to 3.65,P=0.11).Exercise therapy could also reduce the Neck Disability Index score(MD=-11.88,95%CI-16.09 to-7.68,P<0.001),and it was no significant in the Short-Form-36 score(MD=19.04,95%CI-3.00 to 41.08,P=0.09). Conclusion Exercise therapy can improve head posture,pain,motion of forward flexion and lateral flexion,endurance of the cervical flexors and joint position sense,and the overall function in patients with CNSNP.However,fur-ther researches are needed to verify the effects on cervical backward flexion and rotation,and quality of life.

Objective:To understand the current state of ethical competence levels of nurses and analyse the factors that influence them, in order to inform the development of targeted training programmes.Methods:This study adopted a cross-sectional survey method and used convenience sampling to select 825 clinical nurses from Tianjin Chest Hospital as the survey objects from July to August, 2023, and a questionnaire survey was conducted using the General Information Questionnaire, the Ethical Competence Scale, Ethical Competence Support Scale, and Ethical Safety Scale.Results:A total of 818 valid questionnaires were retracted. Among the 818 nurses, 48 were males and 770 were females, the age was (33.19 ± 7.40) years. The total score of nurses ′ Ethical Competence, Ethical Competence Support and Ethical Safety were (118.08 ± 19.96), (215.07 ± 32.02), (48.93 ± 7.55) points, all of which were at a high level. The total score of nurses ′ ethical competence were positively correlated with ethical competence support and ethical safety ( r=0.856, 0.830, both P<0.01); multivariate linear regression analysis showed that the department, the level of ethical competence support, and the level of ethical safety were the influencing factors of the level of ethical competence ( t=5.19, 12.35, 3.88, all P<0.01). Conclusions:Nurses ′ ethical competence, ethical competence support, and ethical safety were at a high level, and the department, the level of ethical competence support, and the level of ethical safety were the factors influencing the level of ethical competence. Nursing managers can provide more ethical education and address ethical issues in multiprofessional discussions, strengthen organizational and personal support for nurses ′ ethical competence, improve nurses ′ ethical safety, and help them implement good ethical care.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective:To explore the mechanism of Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction (hereinafter referred to as " Sanyang combined treatment" ) in alleviating colon injury in mice infected with influenza virus by transcriptome sequencing technique.Methods:The mouse model of colonic injury caused by influenza virus was induced by intranasal drip of influenza A virus H1N1 suspension. The mice were divided into Control group, Model group, and Sanyang combined treatment (SCT) group. Model group and SCT group were fed with PBS and Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction respectively. Seven days later, the colon tissues of each group were taken, the colon length and pathological damage were observed, and the transcriptome was sequenced to screen the significantly different genes between the SCT group and model group for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis(GSEA).Results:After the therapy with SCT, the length of the colon of mice was significantly improved and the pathological injury of the colon was reduced. There are 92 differentially expressed genes between the SCT group and the model group. GO analysis indicated that the differential genes were enriched in biological processes such as regulation of cytokine and chemokine production, inflammatory response, defense response, immune response, regulation of NF-κB inducing kinase(NIK)/Nuclear factor-κB(NF-κB) signal and Mitogen-activated protein kinase(MAPK) cascade, as well as cell components related to intestinal barrier such as brush border membrane, brush border and microvilli. KEGG analysis indicated that the differential genes were enriched in Toll-like receptor signaling pathway, intestinal immune network for IgA production, complement and coagulation cascade, and Peroxisome proliferator-activated receptor(PPAR) signaling pathway. GSEA indicated that the intestinal immune network for IgA production, PPAR signaling pathway, propionic acid metabolism and butyrate metabolism were significantly up-regulated after the intervention with SCT, while apoptosis and MAPK signaling pathway were significantly down-regulated.Conclusions:Sanyang combined therapy can protect the intestinal tract of mice infected with influenza virus mainly through immunity, inflammation and metabolism pathways.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Aim To investigate the protective effect of essential oil from Fructus Alpiniae Zerumbet (EOFAZ ) on type 2 diabetes-induced pancreatic injury in mice and its mechanism.Methods After C57 BL/6 mice fed with high-sugar and high-fat ( HFS) feed developed insulin resistance, streptozotocin ( STZ, 120 mg • kg 1 ) was injected intraperitoneal^ to establish type 2 diabetes model ( DM ) , then DM mice were randomly divided into: diabetes group ( DM ) , EOFAZ low-dose group (90 mg • kg 1 ) , EOFAZ high-dose group ( 180 mg • kg"1 ) , and metformin group (250 mg • kg 1 ).Healthy mice were randomly divided into : normal group and EOFAZ toxicity group ( 180 mg • kg"1).EOFAZ group and metformin group were given EOFAZ and metformin,while normal group and DM group were given an equal volume of normal saline once daily.After eight weeks of continuous intragastric administration, the mice were sacrificed, and the blood was collected to measure fasting blood glucose.HE staining was used to observe the pathological morphology of the pancreas; Western blot was used to analyze the expression of p62, Keleh-like epiehlorohvdrin-related protein 1 ( Keapl ), nuelear factor E2-related factor 2 ( Nrf2 ), and heme oxygenase- 1 ( HO-l ) , anti-apoptotic protein ( Bcl-2) and pro-apoptotic protein ( Bax).Immunohis- tochemistry was used to analyze the expression of Nr£2 in pancreatic tissue.Results Compared with DM group, after administration of EOFAZ , the pathological morphology of pancreas was significantly improved; Keapl , Bax protein expressions were significantly down-regulated and p62, Nrf2 , Ho-1 , Bcl-2 protein expressions were up-regulated ( P <0.05 ).Conclusions EOFAZ has a significant improvement effect on pancreatic injury induced by diabetes, and its effect may be related to the activation of p62/Keapl/Nrf2 to regulate apoptotic response.

OBJECTIVE：To establish th e method for the determination of related substances in fidaxomicin raw material. METHODS：The detection ability of NP-HPLC-UV ，RP-HPLC-ELSD and RP-HPLC-UV systems for the related substances in fidamycin raw material was investigated and the best chromatographic system was selected . The HPLC detection method for the related substances was established. The detection was performed on Agilent Eclipse XDB C 18 column with mobile phase A consisted of 0.2％ triethylamine buffer solution （pH 3.8）-acetonitrile（55∶45，V/V），mobile phase B consisted of 0.2％ triethylamine buffer solution（pH 3.8）-acetonitrile（20∶80，V/V）at the flow rate of 1.0 mL/min（gradient elution ）；the detection wavelength was set at 230 nm，and column temperature was 35 ℃；the sample size was 10 µL. Calculation of the content of related substances was principal component self-control method without correction factor. RESULTS ：The impurities C and F could not be separated effectively in NP-HPLC-UV system. In RP-HPLC-ELSD system ，only impurities C ，D，E and F could be detected. In RP-HPLC-UV system ，11 impurities could be detected. In the study of methodology ，the linear ranges were 0.5-20.0 μg/mL for fidaxomicin（R2＝0.999 9）；the LOD was 0.05 ng，LOQ was 0.15 ng；RSDs of reproducibility and intermediate precision tests were less than 2.0％（n＝6）；average recovery was 98.4％（RSD＝3.6％，n＝9）. The sum of impurities in 3 batches of raw materials were 0.53％，0.51％，0.51％，respectively. CONCLUSIONS ：The effect of detecting impurities by RP-HPLC-UV are the best. Established method is specific and sensitive ，and can be used for the determination of related substance in fidaxomicin raw material.

To study the microbiological contamination of kitchen dishcloths in Chinese housholds, 1010 'in-use' kitchen dishcloths were collected from residential premises in Beijing and Shanghai, and they were sent to the laboratory for microbiological quality analysis. The aerobic plate counts for dishcloths were 10-109 cfu/cm2 in the range of 150 cfu/cm2 to 1.776×109 cfu/cm2 (Beijing) and 62.5 cfu/cm2 to 8.75×108 cfu/cm2 (Shanghai). Nineteen species of bacteria were detected in the dishcloths, most of which were conditional pathogenic bacteria. This study found a significant difference in the aerobic plate counts of dishcloths with regard to type, number of the days used, activities used for, and some family factors. The findings of the study highlight the potential for contamination of kitchen dishcloths within homes.
China ; Environmental Microbiology ; Household Articles