Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Microgravity-induced cardiac remodeling presents a substantial challenge that constrains the advancements in the international space industry,which mainly manifests as alterations in the morphology,structure,and function of the heart.This paper analyzed the core pathogenesis and treatment of microgravity-induced cardiac remodeling based on the theory of"yang transforming qi and yin forming shape"in Huangdi Neijing."Yang transforming qi"reflects the changes in cardiac function,whereas"yin forming shape"reflects the changes in cardiac morphology and structure.Based on the basic and clinical research of space cardiac dysfunctions,the core pathogenesis of microgravity-induced cardiac remodeling is the insufficiency of"yang transforming qi",accompanied by yin excess and yang deficiency due to excessive"yin forming shape"in the early stage,which evolves into deficiency of both yin and yang in the late stage.Thus,this paper specifically refined the treatment methods and corresponding formulas,including warming viscera yang to transform qi,draining yin blood to restore yang qi,and consolidating yin and yang to nourish primal energy.These insights provide systematic theoretical support and conceptual inspiration for the traditional Chinese medicine treatment of microgravity-induced cardiac remodeling.

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

Objective:To describe the temporal trend of disease burden of idiopathic epilepsy in China from 1990 to 2021 and predict the incidence of idiopathic epilepsy in China from 2022 to 2035 to provide references for the formulation of relevant health policies and measures.Methods:Based on data from the Global Burden of Disease Study 2021 (GBD 2021) database regarding idiopathic epilepsy in China, changes in disease burden from 1990 to 2021 were acquired. Disease burden was quantified using age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate (ASDR) and their 95% uncertain interval (UI). Temporal trend analysis was performed using a linear regression model to estimate the estimated annual percent change (EAPC) and annual percentage change (APC) in incidence of idiopathic epilepsy and their 95% CI. Additionally, incidence and number of patients with idiopathic epilepsy in China from 2022 to 2035 were predicted using Bayesian age-period-cohort model. Results:The ASIR of idiopathic epilepsy increased from 22.35 per 100,000 population in 1990 (95% UI: 15.04-30.92 per 100,000 population) to 28.19 per 100,000 population in 2021 (95% UI: 19.03-37.89 per 100,000 population), with an EAPC of 0.12% (95% CI: -0.10%-0.34%); ASPR of idiopathic epilepsy increased from 189.27 per 100,000 population in 1990 (95% UI: 132.48-252.95 per 100,000 population) to 214.71 per 100,000 population in 2021 (95% UI: 150.10-278.56 per 100,000 population), with an EAPC of -0.32% (95% CI: -0.57%-0.06%); ASMR of idiopathic epilepsy decreased from 1.86 per 100,000 population in 1990 (95% UI: 1.59-2.24 per 100,000 population) to 0.80 per 100,000 population in 2021 (95% UI: 0.67-1.00 per 100,000 population), with an EAPC of -2.96% (95% CI: -3.09%-2.82%); ASDR of idiopathic epilepsy decreased from 178.60 per 100,000 population in 1990 (95% UI: 143.44-220.63 per 100,000 population) to 101.39 per 100,000 population in 2021 (95% UI: 72.51-139.40 per 100,000 population), with an EAPC of -2.38% (95% CI: -2.54%-2.22%). The prediction model showed that by 2035, the prevalence of idiopathic epilepsy in China will be 28.27 per 100,000 (95% CI: 23.19-38.66), with an estimated 394,928 incident cases (95% CI: 324,037-540,128). Conclusions:From 1990 to 2021, the ASIR and ASPR of idiopathic epilepsy in China show an upward trend, while the ASMR and ASDR hace a decline trend. Incidence of idiopathic epilepsy in China is expected to remain stable over the next decade.

Objective To explore the effect of prominent cortical vein(PCV)sign on the clinical prognosis of patients undergoing endovascular recanalization for acute anterior circulation cerebral infarction.Methods A total of 102 patients with acute anterior circulation large-vessel occlusion in Zhongshan Municipal Hospital of Tradiontional Chinese Medicine from January 1,2020 to December 21,2022,who received endovascular recanalization,were enrolled in this study.The clinical data and radiographic materials were collected.According to whether PCV sign was present or not,the patients were divided into PCV group and non-PCV group.The clinical data were compared between the two groups.Logistic regression analysis was used to analyze the correlation between the postoperative 90-day mRS score and the occurrence of PCV.Results Compared with non-PCV group,in PCV group the incidence of atrial fibrillation was even higher,and the good rate of collateral compensation was even lower,and the postoperative(7±2)-day NIHSS score was even lower;the differences in above indexes between the two groups were statistically significant(all P＜0.05).Ninety days after treatment,the proportion of patients having modified Rankin Scale(mRS)score ≤2 points in the non-PCV group was 76.3％,which was higher than 58.6％in the PCV group,but the difference was not statistically significant(P=0.074).Logistic regression analysis indicated that a positive correlation existed between the presence of PCV sign and atrial fibrillation(OR=9.679,95％CI=1.264-74.364)and a negative correlation existed between the presence of PCV sign and good collateral compensation(OR=0.015,95％CI=0.033-0.331).No relationship existed between the postoperative 90-day good prognosis and the presence of preoperative PCV sign(OR=2.078,95％CI=0.680-6.348),but patient's age,preoperative intravenous thrombolysis were negatively correlated with the preoperative Alberta Stroke Program Early CT(ASPECT)score(P＜0.005).Conclusion In patients with anterior circulation acute ischemic stroke(AIS),the occurrence of PCV sign is associated with the impaired collateral compensation and atrial fibrillation,but its impact on the clinical outcomes of patients after receiving reperfusion therapy remains uncertain.PCV sign may be used as a potential evaluation indicator for inadequate cerebrovascular collateral compensation.

Objective:To explore the influences of FibroScan detection on the pregnancy outcomes of pregnant rats transfected with hepatitis B virus and the growth of their offspring rats.Methods:Sixty SPF-grade SD rats with a male-to-female ratio of 5∶1 were selected，randomly divided the female rats into the groups of mid-pregnancy with hepatitis B，late-pregnancy with hepatitis B，normal mid-pregnancy，normal late-pregnancy，and control group，and the rats in the mid-pregnancy and late-pregnancy groups were subjected to FibroScan testing on the 10th and 15th days of gestation respectively. The number of offspring rats in each group was randomly reduced to 10 on the 3rd day after delivery，and the offspring rats were divided into the groups of mid-pregnancy with hepatitis B，late-pregnancy with hepatitis B，normal mid-pregnancy，normal late-pregnancy，and control group. The pregnancy outcome levels of pregnant rats were observed by adopting a stratified analysis strategy，including differences in weight changes，number of deliveries，fetal rat outcomes，lactation conditions，litter size，and litter weight. The growth levels of offspring rats，including differences in weight，body length，tail length，and the time of fur growth，tooth eruption，eye opening，and ear standing on the 21st day were observed，and the survival rate of the offspring rats was compared.Results:With regard to the pregnancy outcome levels of the pregnant rats，there were no statistically significant differences in weight changes during pregnancy among the five groups of pregnant rats［ F（4，45）=2.627，Adjusted P=0.222］. There were also no statistically significant differences in the number of deliveries，fetal rat outcomes，and lactation conditions（Adjusted P=1.000）. The number of deliveries［ F（4，21.095）=2.280，Adjusted P=0.222］and litter weight［ F（4，20.128）=2.159，Adjusted P=0.222］showed no statistically significant differences. After correction using the BH method，none of the indicators showed significant differences（ P>0.05）. In terms of the growth levels of the offspring rats，among the five groups of offspring rats，there were no statistically significant differences in body weight on the 21st day［H（4）=11.623，Adjusted P=0.135］，body length on the 21st day［H（4）=10.962，Adjusted P=0.135］，and tail length on the 21st day［H（4）=9.126，Adjusted P=0.058］. Besides，the differences in the time of fur growth，tooth eruption，eye opening，and ear standing［H（4）=0.000，Adjust P=1.000］showed no statistical significance. The survival rate on the 7th day，14th day，and 21st day was 100%，with no significant differences（Adjusted P=1.000）. After correction using the BH method，none of the indicators showed significant differences（ P>0.05）. Conclusion:FibroScan detection had no significant influences on the pregnancy outcomes of pregnant rats with hepatitis B or on the growth of their offspring rats in multiple stages，dimensions，and indicators，indicating that FibroScan detection is safe for pregnant rats. This research provides an animal experimental basis for the safe use of FibroScan in pregnant women with chronic HBV infection.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective To explore the regulatory role of N-methyl berbamine(N-MB)in intracellular calcium homeostasis in H9c2 car-diomyocytes,and,thereby,clarify the possible mechanism of the myocardial protective effect of N-MB.Methods Binding of N-MB to CaV1.2 channels was simulated using the MOE software,and the binding affinity and binding mode were determined.The hCaV1.2 gene was transfected into HEK293 cells,and the effect of N-MB(30 μmol/L)on the CaV1.2 current was detected using the whole-cell patch clamp technique.In addition,a Fluo 3-AM fluorescent probe was loaded into H9c2 cardiomyocytes,and the effect of N-MB(3,30 μmol/L)on intracellular calcium ion concentration was observed under a laser confocal microscope.The effect of N-MB(3,30 μmol/L)on the expression of Ca2+regulation-related genes Cacna1c,Cacnb2,Ryr2,Serca2a,and Ncx1 in H9c2 cardiomyocytes was examined using real-time quantitative PCR.Results N-MB was predicted to bind to CaV1.2 channels.The binding sites mainly involved Phe1191,Thr1420,and Asn771,and the binding modes were H-donor,pi-pi,and pi-H.N-MB(30 μmol/L)significantly inhibited CaV1.2 currents,with an inhibition rate of 76.09％±7.41％.The fluorescence intensity of intracellular Ca2+level in H9c2 cardiomyocytes was significantly enhanced with N-MB treatment(3,30 μmol/L,P＜0.01).Compared with the control group,differences in the expression of Cacna1c,Serca2a,and Ncx1 in H9c2 cardiomyocytes were not significant after N-MB(3,30 μmol/L)intervention(P＞0.05),whereas the expression of Cacnb2 significantly reduced(P＜0.001)and the expression of Ryr2 significantly increased(P＜0.05).Conclusion N-MB binds to CaV1.2 calcium channels.N-MB may regulate intracellular calcium homeostasis by inhibiting calcium currents by decreasing the gene expression of CaV1.2 calcium channels.Additionally,N-MB may also increase intracellular Ca2+concentration by promoting the expression of Ryr2,which could be the mechanism underlying the myocardial protective effect of N-MB.

Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.

Acute large vessel occlusion stroke(ALVOS)of anterior circulation is associated with severe clinical manifestations and high rates of disability and mortality.Mechanical thrombectomy has emerged as the primary therapeutic intervention.However,post-procedural outcomes remain highly variable,and patients continue to face elevated risks of poor prognosis.Machine learning,a transformative tool in medical research,enables comprehensive analysis of multimodal data to identify specific biomarkers and improve the accuracy of predictions for clinical outcomes and adverse events.This review summarized the latest developments in machine learning applications aim at predicting post-thrombectomy prognosis and risk of adverse event,including futile recanalization,hemorrhagic transformation,and malignant cerebral edema in patients with anterior circulation ALVOS in order to provide a basis for developing personalized treatment plan and improve their clinical prognosis.