OBJECTIVE To explore the effects of leonurine on growth arrest-specific protein-6 （GAS6）/Axl signaling pathway， and clarify its mechanism of alleviating myocardial injury in rats with coronary heart disease. METHODS The rat model of coronary heart disease was constructed； successfully modeled rats were randomly separated into model group， leonurine low- dose and high-dose groups （intragastric administration of leonurine 25， 100 mg/kg+intraperitoneal injection of normal saline 75 mg/kg）， and leonurine high-dose+GAS6/Axl signaling pathway inhibitor group （intragastric administration of leonurine 100 mg/kg+ intraperitoneal injection of R428 75 mg/kg）， with 12 rats in each group. Additional 12 normal rats were selected as control group. Each administration group was given relevant medicine； control group and model group were given a constant volume of normal saline intragastrically and intraperitoneally， once a day， for 48 consecutive days. After administration， the heart function of rats， and serum levels of inflammatory factors and myocardial injury markers were detected； the pathological morphology of myocardial tissue was observed； the myocardial cell apoptosis rate， the expressions of apoptosis and GAS6/Axl signaling pathway-related proteins were determined. RESULTS Compared with control group， model group showed disorders in the arrangement of myocardial cells and myocardial fibers， hypertrophy of myocardial cells， and nuclear condensation； left ventricular ejection fraction， left ventricular fractional shortening， ratio of early-diastolic and late-diastolic motion velocity of the mitral ring， the protein expression of GAS6， B-cell lymphoma 2/B-cell lymphoma 2 associated X protein and phosphorylated Axl/Axl ratios were decreased significantly （P＜0.05）. The levels of tumor necrosis factor-α， interleukin-1β， interleukin-6， creatine kinase isoenzyme， troponin Ⅰ and myoglobin， the cell apoptosis rate， and cleaved caspase-3/caspase-3 ratio were increased significantly （P＜0.05）. Leonurine could obviously improve the above pathological conditions and detection indicators （P＜0.05）， and the effect of leonurine high-dose group was more significant than that of leonurine low-dose group （P＜0.05）； R428 treatment could reverse the ameliorating effect of high-dose of leonurine on myocardial injury in rats with coronary heart disease （P＜0.05）. CONCLUSIONS Leonurine can alleviate myocardial injury in rats with coronary heart disease， and its mechanism of action is related to the activation of the GAS6/Axl signaling pathway.

Objective: To examine the association between visceral fat metabolic levels and cardiovascular disease (CVD) among middle-aged and elderly population, so as to provide the evidence for the early identification and prevention of CVD risk in this population. Methods: Based on the database of the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, baseline demographic information, lifestyle, disease history, and CVD status of participants aged ≥45 years were collected. Data on height, weight, waist circumference, and blood biochemical indicators from 2012 and 2015 were collected and used to calculate the metabolic score for visceral fat (METS-VF) and cumulative METS-VF, enabling an assessment of visceral fat metabolism levels. The K-means clustering algorithm was applied to analyze the categories of METS-VF. Multivariable logistic regression models were used to analyze the association between different METS-VF categories, cumulative METS-VF and CVD. A restricted cubic spline model was employed to examine the dose-response relationship between cumulative METS-VF and CVD. Results: A total of 3 146 participants were included, with a median age of 57.00 (interquartile range, 12.00) years. There were 1 405 males (44.66%) and 1 741 females (55.34%). METS-VF was clustered into three distinct categories: a persistently low-level group, a persistently moderate-level group, and a persistently high-level group, comprising 497, 1 302, and 1 347 individuals, accounting for 15.80%, 41.39%, and 42.82%, respectively. By the 2020 follow-up, there were 540 cases of CVD, with an overall prevalence of 17.16%. The prevalence of CVD among different METS-VF categories were 12.47%, 14.36%, and 21.60%, respectively. Multivariable logistic regression analysis showed that, after adjusting for demographic factors, lifestyle, and disease history, compared with the persistently low-level group, the persistently high-level group had a higher risk of CVD (OR=1.710, 95%CI: 1.263-2.342). Cumulative METS-VF was positively associated with CVD risk (OR=1.197, 95%CI: 1.113-1.289). Restricted cubic spline analysis indicated a linear relationship between cumulative METS-VF and CVD risk (P for nonlinearity >0.05). Conclusion Persistently high levels of METS-VF can increase the risk of CVD among middle-aged and elderly population, and there is a positive dose-response relationship between cumulative METS-VF and CVD risk.

Objective:To explore the clinical value of arterial partial pressure of carbon dioxide (PaCO 2) combined with Wells score in predicting acute pulmonary embolism (PE). Methods:Patients with suspected acute PE admitted to Emergency Department of Beijing Chaoyang Hospital, Capital Medical University from January 1, 2016 to August 31, 2021 were screened. Patients with positive computed tomography pulmonary angiography (CTPA) results were classified as the PE group, and those with negative CTPA results were classified as the non-PE group. Demographic characteristics, symptoms, vital signs, underlying diseases, risk factors for venous thrombosis, arterial blood gas analysis and Wells scores were statistically analyzed and compared between the two groups, and the clinical efficacy of PaCO 2 combined with Wells score in predicting acute PE was evaluated. Results:A total of 1 869 patients with suspected acute PE were screened, and 1 492 patients were finally selected. There were 537 cases in the PE group and 955 cases in the non-PE group. The frequency of chest pain, dyspnea, unilateral lower limb edema, history of PE or deep venous thrombosis, history of surgery or immobilization within 3 months, history of fracture within 3 months, active malignant tumor, elevated Wells score and reduced PaCO 2 in the PE group was significantly higher than that in the non-PE group (all P< 0.05). The area under receiver operating characteristic (ROC) curve (AUC) of Wells score was 0.784 (95% CI: 0.758-0.810), and the sensitivity and specificity of predicting acute pulmonary embolism were 61.64% and 88.48%, respectively. The AUC of reduced PaCO 2 was 0.679 (95% CI: 0.651-0.707), and the sensitivity and specificity of predicting acute pulmonary embolism were 79.89% and 55.92%, respectively. The AUC of reduced PaCO 2 combined with Wells score was 0.837 (95% CI: 0.816-0.858), and the sensitivity and specificity of predicting acute pulmonary embolism were 74.12% and 77.07%, respectively. The AUC of reduced PaCO 2 combined with Wells score was significantly greater than the AUC of Wells score ( P<0.001) and the AUC of reduced PaCO 2 ( P<0.001). Conclusions:The efficacy of PaCO 2 reduction combined with Wells score in predicting acute PE was superior to that of either of them alone. This was a beneficial supplement to the screening of patients with acute PE, and would also help reduce the abuse of CTPA in the emergency department.

Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.

Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of different portal perfusion pressures on attenuating hepatic injury from donor after cardiac death(DCD).Methods:All rat livers were subjected to in situ warm ischemia for 30 min after cardiac attest and thereafter stored for 8 h under cold preservation. Six livers were harvested and regarded as static cold storage(group CS, n=6). In experimental group, liver received an ex vivo dual NMP with oxygenated perfusion via hepatic artery for 2 h after cold storage. Hepatic injury was assessed and compared from perfused livers with full portal vein pressure(group M1, n=6)and low portal vein pressure(group M2, n=6). The evaluation parameters included perfusion flow, liver enzymes of perfusate, pathological changes by hematoxylin-eosin staining, Suzuki histological criteria, expression of activation markers of polymorphonuclear neutrophils and macrophages, myeloperoxidase (MPO)and CD68 by immunohistochemistry, level of malondialdehyde(MDA)and activity of superoxide dismutase(SOD). Results:In experimental group during NMP, perfusion flows tended to increase when portal pressures were stabilized in groups M1 and M2.Perfusion flow during NMP 60~120 min was significantly higher than during NMP 0~20 min.After NMP with full portal pressure, hepatic sinusoidal congestion, hepatocyte necrosis, steatosis and Suzuki criteria were lower in group M1 than those in group CS( P<0.05). Compared with group M1, lower hepatic injury was characterized with a lower change of liver enzymes in perfusate( P<0.05), a better histological evaluation( P<0.05), a lower level of MDA and a higher activity of SOD( P<0.05), lower expressions of CD68 and MPO ( P<0.05)and lower levels of TNF-α and IL-6( P<0.05)in perfused liver. Conclusions:The ex vivo dual NMP with oxygenated perfusion via hepatic artery mimics liver perfusion under the physiological conditions.NMP with a lower portal pressure can attenuate hepatic ischemia-reperfusion injury and confer a better protection against liver damage from DCD.

Objective:To investigate the drug resistance and pathogenic mechanism of a uropathogenic Escherichia coli (UPEC) strain UPEC132 at the genome-wide level. Methods:The susceptibility of UPEC132 strain to 16 antimicrobial agents was determined by minimum inhibitory concentration (MIC) assay. The UPEC132 strain was genotyped by multilocus sequence typing (MLST). The three-generation sequencing platform was used to sequence and assemble the whole genome of the UPEC132 strain. Drug resistance and virulence gene function annotations were predicted by Prodigal software and screened by using genome database. Genome sequences of the UPEC132 strain and 23 other UPEC strains collected from GenBank were phylogenetically analyzed, and a phylogenetic tree was constructed by RAxML software.Results:The UPEC132 strain was resistant to ampicillin, ampicillin/sulbactam, tetracycline, erythromycin, chloramphenicol and cefazolin. Its genotype was ST10522 by MLST. The whole genome of the UPEC132 strain included one complete genome (chromosome) and two plasmid sequences. The sequence sizes of the chromosome and plasmids 1 and 2 were 5 234 468 bp, 117 139 bp and 101 356 bp, and the guanine-cytosine (GC) content was 50.48%, 49.05%, and 54.04%, respectively. There were 4 856, 140 and 116 genes annotated in the chromosome and plasmids 1 and 2, respectively. Drug resistance genes were mainly distributed in the chromosomal genome, mainly including the multidrug resistance efflux pump gene clusters. Only blaTEM-1 and tetG genes were carried in the plasmid 2. Virulence genes were also mainly distributed in the chromosome genome, including nine pilus adhesins, five iron uptake systems and three secretory toxins. Gene clusters encoding Afa and type Ⅳ fimbriae were located on plasmids 1 and 2, respectively. The phylogenetic tree showed that the UPEC132 strain was not in the same branch with either of the 23 UPEC strains. Conclusions:The UPEC132 strain belonged to ST10522, which was a newly named ST type of Escherichia coli and first reported at home and abroad. The genome-wide genetic information of the UPEC132 strain was fully revealed. The multidrug resistance genes and virulence genes carried by the UPEC132 strain were associated with its drug resistance and pathogenicity.

Objective To explore the role and mechanism of inducible nitric oxide synthase inhibitor 1 400W in alleviating ischemia-reperfusion injury of human intrahepatic bile duct epithelial cells.Methods Human intrahepatic bile duct epithelial cells (HIBEC) in logarithmic phase were inoculated into culture plate at an appropriate density.The samples were randomly divided into control group (group C),ischemiareperfusion group (group I/R) and ischemia-reperfusion + 1 400W group (group I/R + 1 400W).Group C was cultured routinely;cells in I/R and I/R + 1 400W groups were placed in a three-gas incubator for 12h for simulating ischemia and then normal culture for 6h for simulating reperfusion.The I/R + 1 400W group had a final concentration of 100 μmol/L of 1 400W before ischemia and hypoxia.After reperfusion,cells and culture medium were collected,CCK 8 was used for detecting cell vitality,microplate method for detecting the content of lactate dehydrogenase (LDH) in culture medium,AnnexinV-FITC/PI double stain for detecting apoptosis level,Western blot for analyzing the expressions of endoplasmic reticulum stress (ERS)related protein cysteinyl aspartic acid protease 12 (caspase-12),glucose regulatory protein 78 (GRP78) C/EBP homologous protein (CHOP) and inducible nitric oxide synthase (iNOS).Results As compared with group C,cell viability significantly decreased in I/R and I/R+ 1 400W groups (53.8％ ± 2.3％ vs.100％,66.5 ％ ± 2.8 ％ vs.100 ％) (P＜0.05) while LDH increased markedly in cell culture medium (287.4 ±9.0U/L vs 120.2 ± 8.7U/L,212.0 ± 8.3U/L vs 120.2 ± 8.7U/L) (P＜0.05).Apoptosis accelerated markedly (41.5％±2.3％ vs5.2％±0.5％,32.7％± 1.8％ vs 5.2％±0.5％) (P＜0.05) and the expressions of caspase-12,GRP78,CHOP and iNOS spiked (P＜0.05);as compared with I/R group,cell viability of I/R+ 1 400W group rose while LDH,apoptosis level,caspase-12,GRP78 and CHOP declined in cell culture medium (P＜0.05).Conclusions 1 400W may alleviate ischemia-reperfusion injury of human intrahepatic bile duct epithelial cells and its mechanism may be correlated with a suppression of endoplasrnic reticulum stress.

Objective To analyze the characteristics of antibiotic resistance in group A Streptococ-cus ( GAS) strains isolated from children with scarlet fever in Tianjin in order to provide reference for clinical drug administration. -ethods GAS strains were collected from 2011 to 2016. A total of 276 isolates were analyzed by antibiotic susceptibility test and emm typing. Results All of the isolates were susceptible to penicillin, cefazolin and vancomycin, while 98. 2％ were susceptible to both chloramphenicol and levofloxa-cin. The resistance rates to azithromycin, erythromycin, clarithromycin, clindamycin and tetracycline were 97. 8％, 97. 1％, 94. 2％, 94. 2％ and 79. 3％. The concomitant resistance to erythromycin, azithromycin, clarithromycin, clindamycin and tetracycline was 73. 2％. The resistance rates of GAS strains isolated from different years to tetracycline, clindamycin, clarithromycin, erythromycin and azithromycin were significantly different. A statistically significant difference was found between the percentages of emm12 and emm1 strains resistant to tetracycline (84. 0％ vs 59. 5％, χ2=13. 820, P=0. 000). Conclusions The isolated GAS strains are sensitive toβ-lactams and highly resistant to macrolide antibiotics, clindamycin and tetracycline. Penicillin remains the preferred treatment for GAS infection and cephalosporins may be used as a substitute if the patient is allergic to penicillin.

Objective To study the rate of kidney function decline and the influencing factors in the aged population. Methods This was a prospective population-based study of 468 participants aged 65 years and older. All participants’ general health information and serum creatinine levels were collected as the baseline. After a 3-year follow-up ,the serum creatinine level of each participant was measured again.Kidney function was assessed with estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease-Epidemiology Collaboration ( CKD-EPI ) equation. Outcomes of interest were mean eGFR decline and rapid decline in eGFR (annual eGFR loss≥3 ml·min－1·1.73 m －2).Risk factors were analyzed with Logistic regression. Results At baseline ,the mean age of participants was(78.4 ± 8.7)years and the mean eGFR was(74.8 ± 14.5)ml ·min－1·1.73 m －2.Annual eGFR decline was 1.5 ml·min－1·1.73 m －2,with rapid declines in 149 (32%) participants and stable kidney function in 319 (68%) individuals. The rate of kidney function loss slowed down as the age increased.Baseline eGFR was an independent predictor for rapid kidney function decline. The incidence of rapid kidney function decline in individuals with eGFR ≥ 60 ml· min－1·1.73 m －2was 2.40 times (95% CI :1.16-4.98) higher than that of participants with eGFR＜60 ml·min－1·1.73 m －2after adjustment for confounders. Conclusions Kidney function changes in the community-dwelling elderly in China are heterogeneous. Most elderly individuals do not show appreciable kidney function decline over a 3-year period.

Acute -on -chronic liver failure (ACLF) is characterized by the rapid deterioration of liver function resulting from acute insults in patients with pre -existing liver disease,which is usually correlated with multisystem organ failure .There is still no ideal therapy available for ACLF untill now.An early and accurate evaluation of the prognosis of patients with ACLF is helpful for physicians to optimize treatment strategies and improve the outcome of these patients .This article highlights the characteristics and predictive power of diffrent scoring systems in an attempt to guide the therapeutic strategy and prognostic assessment by reviewing the prognostic models for ACLF in recent years .