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.

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.

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.

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.

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 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.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

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.

AIM:To investigate the effects of Balanophora involucrata Hook.f.(BIH)extracts on bile acid metabolism and liver injury in mice with metabolic dysfunction-associated fatty liver disease(MAFLD)through the gut mi-crobiota-farnesoid X receptor(FXR)axis,and to explore the underlying mechanisms.METHODS:Forty C57BL mice were randomly divided into control group,MAFLD model group,medium-dose BIH group,and high-dose BIH group.The mice in control group received a regular diet,while those in other groups were fed with high-fat diet for 12 weeks to induce MAFLD.The mice in medium-and high-dose BIH groups received 0.598 and 0.299 g/kg BIH solution,respectively,while those in control and MAFLD groups received an equivalent volume of normal saline.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured using an automatic biochemical analyzer.Liver morphology,steatosis and fibrosis were assessed by HE,oil red O and Masson staining.Levels of TC,tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in liver tissues,and bile acids in serum and ileum tissues were measured by ELISA.Protein expression of FXR and fibroblast growth factor 15(FGF15)in ileum tissues,and FXR,small heterodimer partner(SHP)and cholesterol 7α-hydroxylase(CYP7A1)in liver tissues were analyzed by Western blot.Intestinal microbiota changes were assessed by 16S rRNA gene sequencing.RESULTS:(1)The MAFLD mice exhibited increased serum TC,TG,LDL-C and bile acid levels,liver TC,TNF-α and IL-6 levels,and lipid deposition.However,BIH intervention improved these factors and increased FXR and SHP pro-teins,but decreased CYP7A1 expression in the liver.The protein levels FXR and FGF15 in the ileum were also elevated.(2)Intestinal flora analysis demonstrated that BIH intervention improved the abundance and diversity of intestinal flora in MAFLD mice.Specifically,there was an increase in Bacteroidetes/Firmicutes ratio and a decrease in Proteobacteria and Verrucomicrobia.At the genus level,abundance of Duncaniella,Muribaculum and Paramuribaculum increased,while He-licobacter decreased.CONCLUSION:Treatment with BIH regulates intestinal flora,decreases FXR levels,enhances CYP7A1 expression,promotes bile acid synthesis,reduces hepatic cholesterol accumulation,and attenuates liver steato-sis and inflammation in MAFLD mice,indicating potential therapeutic effects.