Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To study the learning curve of percutaneous patent foramen ovale (PFO) occlusion guided solely by transthoracic echocardiography (TTE), as well as the success rate and safety of the learning curve.Methods:To retrospectively analyze these patients with indications for PFO occlusion admitted in our department from April 2021 to April 2022, and obtained 100 samples the author's initial cases guided solely by TTE, including 25 men and 75 women, with a mean age of (48.22±10.44) years old.Analyze preoperative baseline data: gender, age, height, weight, body mass index, the tunnel length and size of the PFO measured by transesophageal echocardiography, the grade of contrast-transcranial doppler test, combined atrial septal aneurysm, etc.Operation time, success rate, and complications were analyzed in all patients.Results:With the accumulation of cases, the operation time gradually shortened, accumulated to about 50 cases, the operation time has significantly shortened ( P<0.05), and the learning curve was leveled off after 50 cases ( P<0.05), there was statistical difference.The comparison of the success rate and complication of cases within the learning curve and those after completing the learning curve was no statistical significance( P>0.05). Conclusion:The learning curve of percutaneousc closure of patent foramen ovale guided solely by TTE is long, requiring about 50 cases to complete the learning curve. The success rate and safety of the learning curve are high. This procedure is worth popularizing.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R ²) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Brain ; Brain Injuries ; Computer Simulation ; Finite Element Analysis ; Humans ; Neural Networks, Computer

Objective:To establish an animal model of chronic systemic inflammation with long-term high expression of circulating IL-6 by introducing exogenous IL-6 gene transfer vector.Methods:Recombinant murine IL-6-encoding adeno-associated virus (AAV-IL-6) was constructed. Twenty-one 24-week-old male C57BL/6J mice were randomly divided into three groups with seven in each group: AAV-IL-6 group, vector control (AAV-ctrl) group and blank control group. At 0, 8 and 16 weeks of intervention, the mice in the three groups were injected with AAV-IL-6 (100 μl 0.5×10 10 vp/ml), unloaded AAV (100 μl 0.5×10 10 vp/ml) and the same volume of saline in the tail vein, respectively. IL-6 levels in mouse serum were measured by ELISA. The general condition of mice was observed and blood routine tests were performed. Changes in blood biochemical parameters and C-reactive protein (CRP) levels were detected. At the end of 24-week intervention, the mice were sacrificed and the myocardium, liver, spleen, quadriceps femoris, knee joint and middle femur were taken for HE staining. Results:At 4, 8, 16 and 24 weeks after intervention, serum IL-6 levels were (75.41-169.28) pg/ml in the AAV-IL-6 group, while in the two control groups, the levels were below the lower limit of detection (7.8 pg/ml). At 24 weeks after intervention, the body weight of mice in the AAV-IL-6 group was significantly lower than that of mice in the two control groups; the neutrophil counts and CRP level in the AAV-IL-6 group were higher than those in the two control groups, while the levels of albumin, creatinine, triglyceride and cholesterol were lower than those in the two control groups. There were no differences in the aforementioned parameters between the two control groups. Compared with the blank control group, both AAV-IL-6 and AAV-ctrl groups showed increased lymphocyte counts. All mice had normal liver and kidney functions at the end of intervention. Histopathological findings indicated that the mice in the AAV-IL-6 group had focal infiltration of lymphocytes in the central venous area of the liver and around the myocardial and the skeletal muscle fibers, diffuse infiltration of multinucleated giant cells in the spleen, atrophic skeletal muscle, disorganized growth plate, reduced chondrocyte hypertrophic zone, thinner bone cortex and trabecular, and reduced osteoid. There were no histopathological changes in mice of the two control groups.Conclusions:Repeated tail vein injection of AAV-IL-6 could achieve long-term high expression of circulating IL-6 in mice, which manifested the phenotype of chronic systemic inflammation in preliminary detection and provided a safe, effective and simply accessible animal model for related studies.

Objective 聽 聽To investigate the influence of mechanical and biological valves on clinical benefits of elderly patients with valvular heart disease. Methods 聽 聽We retrospectively analyzed the clinical data of 280 elderly patients with valvular heart disease treated by valve replacement between 2008 and 2014 year. The patients were divided into two groups by tendency score matching including a group A with biological valves and a group B with mechanical valves. Finally, there were 96 patients in each group. There were 43 males and 53 females at age of 64.41卤6.52 years in the group A, 44 males and 52 females at age of 64.07卤6.20 years in the group B. Results 聽 聽The bleeding rate of skin and mucosa of the group B was significantly higher than that of the group A (P<0.05). There was no statistical difference in mortality within 30 days after operation, all-cause mortality, re-hospitalization rate, re-valve replacement rate, combined atrial flutter/atrial fibrillation ratio, drug use, incidence of cerebral infarction, cerebral hemorrhage, new peripheral vascular embolism and visceral hemorrhage, heart function (NYHA) classification, the cumulative survival rate of all the patients during follow-up (P=0.63), or the cumulative survival rate of the patients with no thrombus/hemorrhage (P=0.75) between the two groups (P>0.05). Conclusion 聽 聽Mechanical valve replacement and bioprosthetic valve replacement in the treatment of valvular heart disease in the elderly can achieve similar clinical benefits and both have clinical application value.

Anatomy is an important medical course for international medical students. In order to improve the teaching quality and enhance the extent of students' learning, teachers integrated the theoretical and experimental courses of systemic anatomy, and introduced the "Digital Human" anatomical system to compensate the shortage of models, so as to realize the integrated theory and experiment teaching of systematic anatomy. Practice indicated that integrated teaching mode of theory and experiment was more consistent with the learning habits of foreign students, which improved their learning effect with significant advantages. But there were still some problems in this teaching mode and measures for solving these problems were proposed in this paper.

Objective To investigate the effects of FOXA2 on the proliferation of hepatocellular carcinoma cells and the tumorigenesis of nude mice, and to explore the effect of FOXA2 on the development of hepatocellular carcinoma. Methods Immunohistochemistiy and real-time quantitative PCR were used to detect the expression of FOXA2 in 35 pairs of hepatocellular carcinoma tissues and their matched paracancerous tissues. 293 T cells were used as controls to detect the expression level of FOX A 2 in hepatocellular carcinoma cell lines (HepG2, SMMC-7721 and SK-Hep1) by real-time quantitative PCR. The lentivirus was transfected into HepG2 cells, and there were 3 groups including no virus group (Mock group) , negative control virus group (NC group) and FOXA2-transfected over-expression virus group (FOXA2 group). Plate clone assays were used to detect the effect of FOXA2 on the proliferation of HepG2 cells in vitro and nude mice tumor and formation assays to detect the tumor weight and tumor weight inhibition rate after FOX A2-transfected overexpression of lentivirus-infected cells. Results The results of immunohistochemistry and real-time quantitative PCR showed that the expression of FOXA2 in cancer tissues was significantly lower than that in adjacent tissues (P < 0.01) , And the expression of FOXA2 in hepatoma cell lines (HepG2, SMMC-7721, SK-Hepl) was significantly lower than that of 293 T cells (P < 0.0001). After the lentivirus was transfected into HepG2 cells, the number of clones in the FOXA2 group was significantly less than that in the Mock group and the NC group (P < 0.05). The tumor formation of nude mice showed that the tumor weight of FOXA2 group was smaller than that of the corresponding blank control group and negative control group (P < 0.01).Conclusion FOXA2 is lowly expressed in hepatocellular carcinoma tissues and cells, which has the effect of inhibiting the proliferation of HepG2 cells in vitro and the growth of tumors in nude mice in vivo.

Objective    To compare the effects of transthoracic device closure and surgical closure on ventricular septal defect systemically. Methods    A systematic literature search was conducted using the PubMed, EMbase, The Cochrane Library, VIP, CNKI, CBM, Chinese Clinical Trial Register, ClinicalTrials. gov and Wanfang Database up to July 31, 2016. Quality was assessed and data of included articles were extracted. The meta-analysis was conducted using RevMan 5.0 and Stata 14.0 software. Results    Eleven studies were identified, including 5 RCTs and 6 cohort studies involving 2 504 patients. For success rate, there was no statistical difference between the transthoracic closure group and the surgical closure group in RCT (RR=0.99, 95%CI 0.96 to 1.03, P=0.70); the success rate in the transthoracic closure group was lower than that in the surgical closure group in the cohort study (OR=0.21, 95%CI 0.08 to 0.55, P=0.002). Both  results of RCTs and cohort studies showed that compared with surgical closure, transthoracic device closure reduced duration of the operation (RCT MD=–79.38, 95%CI –95.00 to –63.76, P<0.000 01; cohort study MD=–66.26, 95%CI –71.20 to –61.31, P<0.000 01) and hospital stay (RCT MD=–2.10, 95%CI –2.65 to –1.55, P<0.000 01; cohort study MD=–3.99, 95%CI –6.03 to –1.94, P=0.000 1), and the patients with blood transfusion (RCT RR= 0.04, 95%CI 0.01 to 0.11, P<0.000 01; cohort study OR=0.01, 95%CI 0.00 to 0.13, P=0.001). In the transthoracic closure group the risk of postoperative arrhythmia reduced (RCT RR=0.20, 95%CI 0.13 to 0.32, P<0.000 01; cohort study OR=0.46, 95%CI 0.31 to 0.67, P<0.000 1). In the transthoracic closure group a higher postoperative valvular regurgitation risk in RCT induced (RR=1.45, 95%CI 1.07 to 1.96, P=0.02) and the rate of postoperative valvular regurgitation in cohort study reduced (OR=0.43, 95%CI 0.20 to 0.92, P=0.03). However, there was no statistical difference in postoperative residual shunt (RCT RR=0.96, 95%CI 0.57 to 1.62, P=0.89; cohort study OR=0.52, 95%CI 0.12 to 2.25, P=0.38). Conclusion    Transthoracic device closure can shorten duration of the operation, hospital stay and reduce the patients with blood transfusion and post- and intraoperative arrhythmia risk. Therefore, transthoracic device closure may be a better approach for some ventricular septal defect patients.

Objective To study the effect of lithium chloride on the gap junction in the myocardium under chronic hypoxia.Methods Twenty-five C57BL/6J mice were randomly divided into normoxia group,hypoxia group,normoxic control group,hypoxia + saline group and hypoxia + lithium chloride group.Hypoxia group was treated with 10％ oxygen concentration for 4 weeks.Hypoxia + saline group and hypoxia + lithium chloride group were intraperitoneal injection of saline and lithium chloride.Electrophysiology and cardiac catheterization were used to assess arrhythmias,heart rate and ejection fraction.The expression of Cx43,phosphorylated glycogen synthase kinase 3β(p-GSK-3β) and glycogen synthase kinase 3β (GSK-3β) were detected by Western blot.Results Compared with the normoxia group,the hypoxia group had a faster heart rate [(448 ± 18) bpm vs.(401 ± 13) bpm,P＜0.05),and the ejection fraction was decreased [(56±5)％ vs.73±4)％,P＜0.05],arrhythmia score increased [(3.4±0.5)％ vs.(0.6±0.5)％,P＜0.05],Cx43 expression was decreased.Compared to hypoxia + normal saline group,the heart rate decreased[(412±11)bpm vs.(454±18)bpm,P＜0.05],ejection fraction increased[(69±3)％ vs.(55±4)％,P＜0.05],the score of arrhythmia decreased [(1.8±0.4) ％ vs.(3.0±0.7)％,P＜0.05] in hypoxia + lithium chloride group,the expression of Cx43 and the rate of p-GSK-3β to GSK-3β were increased.Conclusion During the chronic hypoxia,lithium chloride can sustain the gap junction through inhibition of GSK-3β signaling way,which can also reduce the rate of arrhythmia.