Objective To determine the protective effect of isosorbidemononitrate (IM) on myocardial injury after restoration of spontaneous circulation (ROSC)in swine models of cardiac arrest induced by ventricular fibrillation.Methods The experiment was carried out in Animal Lab of Beijing Chao-Yang Hospital,Capital Medical University.Ventricular fibrillation was induced and untreated for 8 min in twenty WhuZhiShan piglets.CPR was performed until ROSC occurred.The animals were randomized (random number)into two groups:IMgroup (n =10)and control group (n =10).IM [2 μg/(kg· min)]or the equivalent volume in saline was administered respectively for 6 h after ROSC.Hemodynamics and post-resuscitation cardiac function were monitored until 24 h after ROSC. Echocardiography and transmission electron microscopy were useed at 72 h after ROSC.Results There was no significant difference in survival rate between the two groups.No significant differences in mean arterial pressures (mmHg)at ROSC 6 h (88.5 ±5.6 vs.87.8 ±6.0,P =0.790)and ROSC 24 h (89.3 ±3.8 vs.86.9 ± 5.0,P =0.245)between the two groups were found.Cardiac outputs (L/min)were significantly increased at ROSC 6 h (2.40 ±0.17 vs.1.60 ±0.14,P <0.01)and ROSC 24 h (2.49 ±0.17 vs.2.09 ±0.21,P<0.01);and ejection fraction at ROSC 72 h (0.67 ±0.08 vs.0.56 ±0.09,P =0.044)was improved too,and significant differences were found between the two groups.The ultra-structural myocardial injury was ameliorated in the MI group at 72 h after CPR observed by using electron microscopy.Conclusions IM can ameliorate post-resuscitation cardiac dysfunction in porcine models of cardiac arrest induced by ventricular fibrillation.

We constructed prokaryotic recombinant expression vector of P61 gene from Nocardia brasiliensis,expressing P61 protein with biological activity in E.coli,and lay a foundation for further studies related to P61.P61 gene was synthesized and cloned into an expression vector pET-30a(+).The recombinant vector was transformed into Escherichia coli BL21 and induced with IPTG.The production was analyzed with Western blot and the catalase activity of P61 was tested with Catalase Assay Kit.The protein of P61was successfully expressed in E.coli with solubility and high catalase activity,and could be identified by anti-N.brasiliensis sera from mice.The prokaryotic expression plasmid of protein P61 was constructed successfully and can be expressed efficiently in E.coli BL21 cells with higher catalase.

To investigate the effect of MMP-26 on human glioma angiogenesis and the possible mechanism.Methods The MMP-26 plasmid and empty plasmid pcDNA3.1 were stably transfected into U251 cells to establish a nude mice xenograft model,and then an in vitro human tumor tissue-based three-dimensional angiagenic model.Tissue disks were visually assessed over time to determine the percentage of wells that developed an angiogenic response(I％) and the density and length of neovessel growth were graded at intervals using a semiquantitative visual growth-rating scheme (angiogenic index,AI,0-16scale) in groups of MMP-26 transfected U251 cells (U251-MMP-26),pcDNA3.1 vector-transfected U251 cells (U251-pcDNA3.1) and non-transfected U251 cells (U251).RT-PCR and immunohistochemistry were used to detect the expression of mRNA and protein of MMP-26 and VEGF in groups of U251-MMP-26,U251-pcDNA3.1 and U251.Immunohistochemical localization of CD31 was determined in the endothelial tubes invading the fibrin-thrombin clot matrix.Results Immunohistochemical endothelial cell markers CD31 was positive in the vascular tubes invading the fibrin-thrombin clot matrix,confirming their endothelial origin.The angiogenesis results showed that difference of length of micro capillaries,density of branches,and the area occupied between U251-MMP-26 groups and control groups were significant.The percentage of tumor implants that developed invasion (I％) and the angiogenic index AI in U251-MMP-26 group on day 14 were higher than those of U251-pcDNA3.1 group and U251 group (P ＜ 0.05).The trends of I％ and AI in 14 days were significant compared with those in control groups.The expression of mRNA and protein of MMP-26and VEGF in U251-MMP-26 group was significantly higher in U251-MMP-26 group than those in U251-pcDNA3.1 group and U251 group(P ＜0.01).Conclusion The effect of MMP-26 on promoting glioma angiogenesis may be related to the increased expression of VEGF,which can be used as targets for anti-tumor therapy.

HMGB1's role in tumors is complex and diverse,and it exerts its biological function by combining with different receptors.One of the receptors is called RAGE,which is localized to the cell membrane and binds to HMGB1 released outside the cell.The HMGB1/RAGE axis promotes tumor development,moreover,tumor development and its drug resistance are closely related to inflammation.This article mainly reviews the molecular mechanism of HMGB1/RAGE axis in pro-inflammatory and protumor effects in pancreatic,colorectal and liver cancers.We also summarize the research progress of papaverine and its derivatives for the treatment of HMGB1/RAGE axis in tumor inflammation,with aims of providing new ideas for exploring the molecular mechanism of action in tumor inflammation,and providing a new theoretical basis for the research of HMGB1/RAGE axis therapeutics.

Objective To explore the risk factors affecting prognosis of critically ill patients following cardiac surgery, furthermore, to assess severity and keep alarm earlier. Methods A retrospective study was conducted. The clinical data of critically ill patients following cardiac surgery admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from January 1st 2014 to December 31st 2018 were enrolled. The clinical characteristics, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and the worst laboratory examination within 24 hours after ICU admission, and the duration of mechanical ventilation, length of ICU stay, using continuous renal replacement therapy (CRRT), accepting vasoactive agents such as norepinephrine, dopamine or dobutamine and blood products such as red blood cells, plasma or platelets were recorded. The patients were divided into survival group and dead group based on discharge prognosis, and the difference in clinical data between the two groups was compared. Binary multivariate Logistic regression analysis was used to screen the risk factors affecting the prognosis of critically ill patients following cardiac surgery, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of these risk factors. Results In total, 97 patients after cardiac operation were admitted to ICU during the five years. Thirty-two patients were excluded owing to age less than 16 years old, no more than 24 hours of the length of ICU stay, without the outcomes of myocardium enzymes or myocardium markers within the first 24 hours or admitted only for pacemaker. Finally, 65 patients met the criteria, with 40 survived and 25 died. Compared with survival group, APACHEⅡ scores, the level of serum uric acid, serum creatinine (SCr), cardiac troponin T (cTnT), brain natriuretic peptide (BNP), procalcitonin (PCT) and the rate of patients accepting CRRT, vasoactive agents and blood products in dead group were significantly increased with significant differences; however, there was no statistically difference in gender, age, body weight index (BMI), distribution of types of cardiac surgery, ratio of patients suffered from hypertension and diabetes, mean arterial pressure (MAP), white blood cell (WBC), coagulation, length of ICU stay, or duration of mechanical ventilation between the two groups. Binary multivariate Logistic regression analysis showed that APACHEⅡ scores [odds ratio (OR) = 1.123, 95% confidence interval (95%CI) = 1.004-1.257, P = 0.043] and cTnT (OR = 1.496, 95%CI = 1.038-2.158, P = 0.031) were the independent risk factors for prognosis of critical ill patients following cardiac surgery. ROC curve analysis showed that APACHEⅡ score and cTnT had predictive value for prognosis of critical ill patients following cardiac surgery, the best was exerted when APACHEⅡ score combined with cTnT, the area under the ROC curve (AUC) was 0.839, the joint prediction probability was 0.42, the sensitivity was 80.0%, and the specificity was 64.0%. Conclusion APACHEⅡscore and cTnT may be one of independent risk factors for prognosis of critical ill patients following cardiac surgery, and there will be far more greater predictive value when APACHEⅡ score combined with cTnT.

Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.

Objective: To evaluate the clinical effects of full-arch cement-retained implant-supported combined crowns and screw-retained implant-supported bridge dentures in complete or half edentulous patients. Methods : A total of 25 patients with complete or partial edentulous dentures followed up for 1, 3, and 5 years in our hospital from June 2013 to June 2018 and were treated with Straumann bone horizontal implantation, cobalt-chromium stenting and cobalt-chromium porcelain restoration with cement-retained and screw-retained implant-supported fixed dental prostheses to evaluate the accumulative implant survival rate, accumulative prosthesis survival rate, mechanical complications, and biological complications in both groups. Results : There were 25 complete or half edentulous patients who received 165 Straumann implants and 28 implant-supported fixed dental prostheses in this study. There were 11 cases with 69 implants in the cement group and 17 cases with 96 implants in the screw group. The accumulative implant survival rate was 100% in the cement group and 96.9% in the screw group. The accumulative prosthesis survival rate was 100% in both groups. The cumulative peri-implant mucositis rate was 23.2% in the cement group and 29.2% in the screw group, and the peri-implantitis rate was 6.8% in the cement group and 7.3% in the screw group. There was 1 case of porcelain collapse (n=1/11) and no screw of abutment loosening in the cement group and 4 cases of porcelain collapse (n=4/17) and 1 case of screw loosening in the screw group. No fracture of abutment was observed in either group. There was no difference in bone loss between the two groups in the first year (P > 0.05), and a higher rate of bone loss was found in the screw group in the third and fifth years (P < 0.05). There was no difference in the sulcus bleeding index(mSBI) between the two groups in the first year and the third year (P > 0.05) and a higher modified mSBI value in the cement group in the fifth year (P < 0.05). Conclusion The survival rates of the implant and prosthesis for cement-retained or screw-retained implant-supported fixed dental prostheses were both high, but there were more mechanical and biological complications in the traditional cobalt-chromium alloy screw-retainer group. The removal of residual adhesives must be reasonably considered when choosing the cement retention method.

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

To explore the potential mechanism of frankincense volatile oil in the prevention and treatment of cardiac hypertrophy based on in vitro cell experiment and network pharmacology. METHODS: The anti-hypertrophic effect of frankincense volatile oil was investigated by isoproterenol induced H9c2 cardiomyocytes hypertrophy model. The active chemical components and targets of frankincense volatile oil and targets associated with cardiac hypertrophy were obtained by CNKI, Pubmed, Pubchem databases, etc. String database and Cytoscape 3.8.0 software were used to construct protein-protein interaction network (PPI) and a network of "drug-active component-key target-disease" of frankincense volatile oil in order to screen the key targets of frankincense volatile oil against cardiac hypertrophy. The fluorescent quantitative PCR experiments were performed to verify those key targets. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of key target genes were performed using David online analysis tool. RESULTS: In vitro cell experiments showed that frankincense volatile oil significantly inhibited the isoproterenol induced increases in cardiomyocytes surface area and protein synthesis, and upregulations of ANP and β-MHC mRNA. A total of 87 active components and 36 ingredient-disease targets of frankincense volatile oil were screened. Network analysis showed that ESR1, NOS3, PTGS2, TNF, MAPK14, and PPARG were key targets. Fluorescence quantitative PCR experiments results indicated that frankincense volatile oil inhibited isoproterenol induced upregulations of ESR1, PTGS2, TNF, and MAPK14 mRNA levels, and downregulations of NOS3, PPARG mRNA levels, respectively. In addition, the GO functional enrichment analysis showed that its biological pathways mainly included lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, enzyme binding, etc. The KEGG pathway enrichment analysis included 22 KEGG pathways, which were closely related to VEGF signaling pathway, TNF signaling pathway, sphingolipid signaling pathway and others. CONCLUSION: The active components of frankincense volatile oil may regulate VEGF signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway by acting on ESR1, NOS3, PTGS2, TNF, MAPK14 and PPARG targets, thereby affecting the regulation of lipopolysaccharide-mediated signaling pathway, positive regulation of nitric oxide biosynthetic process, caveola, and enzyme binding, and improving cardiac hypertrophy.