Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

Objective The objective of this study is to investigate whether there is a correlation between a high TyG index(serum triglyceride glucose index)and higher mortality rates among patients undergoing peritoneal dialysis(PD).Methods This study utilized a single-center retrospective cohort as the basis for its methods..From January 1,2007 to December 31,2015,a total of 519 PD patients kept under observation until December 31,2018.There searchers employed the Kaplan-Meier method and Cox proportional hazards modelsto examine the cor-relation between TyG index levels and mortality.Results Over a period of 40.5 months,104(20.0%)individuals with Parkinson's disease passed away,with 55(52.9%)of these deaths attributed to cardiovascular disease(CVD).The serum median TyG index at baseline was 8.44(6.48,11.94).Through Cox regression analysis subject to the adjustments of such parameters as gender,age,body mass index(BMI),presence of cardiovascular disease,hypertension,diabetes mellitus,hemoglobin,serum albumin,serum Ferritin,total cholesterol,renal residual function(RRF),An increased risk of all-cause mortality(HR = 2.22,95%CI:1.43～3.44,P＜0.001)and CVD mortality(HR = 2.50,95%CI:1.34～4.65,P = 0.004)was observed with a higher baseline TyG index(8.44).A comparable impact was observed in the correlation between the average TyG index over time(TA-TyG index)and both all-cause mortality and CVD mortality.(HR = 1.90,95%CI:1.25～2.90,P = 0.003;HR = 2.05,95%CI:1.14～3.70,P = 0.017,respectively).Conclusion PD patients with a higher serum TyG index have a greater risk of all-cause mortality and mortality related to cardiovascular disease.

Objective:A SARS-CoV-2 pseudovirus(PsV)system was established for neutralizing antibody evaluation and virus entry inhibitor screening.Methods:Lentiviral vector plasmids psPAX2,pCDH-Luc and SARS-CoV-2 Spike(S)protein expres-sion plasmids were co-transfected,and harvested pseudoviral supernatant was used to infect ACE2-293T cells.Protein content of p24 was determined to reflect titer of PsV,and expression of S protein in PsV was detected by Western blot.Neutralization capacity of an S protein monoclonal antibody was evaluated using original strain,D614G,Gamma,Delta,Omicron PsV.Two reported virus entry inhibitors,chloroquine and carrageenin,were used to detect effect on entry of Omicron PsV.Results:Lentiviral vector successfully incorporated S protein.Western blot results showed that S protein mutated at 665Y showed a different cleavage form(90 kD)than wild-type full-length S protein(180 kD).Titer of PsV packaged by three plasmids system was higher.Ratio of S protein expression plasmid,transfer plasmid and packaging plasmid at 1∶3∶3 was optimum condition for viral packaging.Titer of PsV packaged under this condi-tion was over 20 ng/ml.PsV could effectively infect ACE2-293T cells,and double reporter gene GFP and firefly luciferase were expressed obviously,whose chemiluminescence values reached 106.Monoclonal antibodies of S protein effectively neutralized four types of PsVs,but neutralization of original strain was 10～30 times greater than that of variant PsV.Virus entry inhibitors,chloroquine and ι-carrageenan significantly inhibited entry of Omicron PsV.Conclusion:SARS-CoV-2 PsV infection system we conducted can simu-late entry of SARS-CoV-2 successfully.Effective pharmacodynamic evaluation of neutralizing antibodies and virus entry inhibitors can be performed efficiently by the system,which can provide a technical platform for evaluation of neutralizing antibody of SARS-CoV-2 and screening of virus entry inhibitors,and would benefit R&D of anti-SARS-CoV-2 drugs.

OBJECTIVE To establish a mouse model of diabetes mellitus(DM)combined with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to investigate the important pathophysiological changes in the development of DM combined with SARS-CoV-2 infection.METHODS Wild-type(WT)mice and transgenic mice expressing the human angiotensin-converting enzyme 2 receptor driven by the cytokeratin-18 gene promoter(K18-hACE2)were randomly divided into the control group,DM group,SARS-CoV-2 spike protein(S)infection group and DM combined with S protein infection group,with 10 to 12 mice in each group.All the mice were induced by 10 weeks of high-fat diet combined with 40 mg·kg-1 streptozotocin(STZ)for 3 days by ip,except those in the control group or S protein infection group.The control group was given the same volume of 0.1 mol·L-1 sodium citrate buffer.Mice in the S protein infection group and DM+S protein infection group were additionally given 50 μL mixture of 15 μg SARS-CoV-2 spike protein and 1 g·L-1 polyinosinic-polycytidylic acid(poly[I:C])via intranasal drops,while the control group was given an equal volume of sterile water.The glucose tolerance level and pancreatic islet β cell function of mice were evaluated via oral glucose tolerance test at the 6th week of high-fat feeding and 1 week after the administration of STZ by ip.From the 6th week of high-fat feeding to 2 weeks after the administration of STZ,the random blood glucose and fasting blood glucose of mice were measured by a blood glucose meter.Blood samples were taken from subman-dibular veins of 3 mice in each group at 24,48 and 120 h after S protein infection,and lung tissues were taken after euthanization.The pathological changes of lungs of DM mice before and after S protein infection were observed by HE staining.Except for the DM group,blood samples were collected before S protein infection and at 6,24,48,72 and 120 h after infection.The levels of plasma interleukin 1β(IL-1β),IL-2,IL-6,IL-10,IL-17,interferon gamma-induced protein 10(IP-10),interferon γ(IFN-γ),tumor necrosis factor α(TNF-α),monocyte chemotactic protein-1(MCP-1)and granulocyte-colony stimulating factor(G-CSF)were detected by Luminex.The plasma levels of heparan sulfate(HS)were measured by enzyme-linked immunosorbent assay.The levels of cytokines and HS were correlated with the degree of pathological damage by Spearman correlation analysis.RESULTS STZ and high-fat diet could induce DM-like expression in mice,and the random blood glucose(P<0.01)and fasting blood glucose(P<0.05)after 1 week in the hACE2-DM group were significantly higher than in the WT-DM group,and the degree of islet function damage in hACE2-DM mice was significantly higher than that of WT-DM mice(P<0.05).Compared with the DM group,the DM+S group showed more severe pulmonary pathological changes after S protein infection,accompanied by a large number of inflammatory infiltrations and thickening of lung interstitial.Compared with the control group,the levels of pro-inflammatory cytokines G-CSF,IL-6 and IP-10 in the plasma of the WT-S group were significantly increased at 6 h after S pro-tein infection(P<0.01),and those of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 were significantly increased at 24 h after S protein infection(P<0.05).Compared with the control group,the plasma levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,MCP-1,G-CSF and IP-10 in the hACE2-S group were significantly increased at 6 h after S protein infection(P<0.05,P<0.01).IL-17 was significantly increased at 24 h and 6 h after S protein infection in the WT-DM+S group and hACE2-DM+S group,respectively(P<0.01,P<0.05).In the hACE2-DM+S group,IFN-γ and IL-1β were signifi-cantly increased in delay to 48 h(P<0.05,P<0.01),and MCP-1 was significantly increased in delay to 72h(P<0.05).Compared with the control group,the level of HS in the plasma of the WT-S group increased significantly(P<0.05,P<0.01)at 6 h and 24 h after S protein infection,but began to decrease at 48 h.At the same time,compared with the WT-S group,the HS level in the WT-DM+S group was slightly increased at 6 h after infection and decreased at 24 h.Compared with the control group,the HS level in the hACE2-S group was significantly increased at 24 h(P<0.01),as was the case with the WT-S group 24 h,48 h and 120 h after S protein infection.At 6 h,24 h and 48 h after S protein infection,the plasma HS level of the hACE2-DM+S group was significantly increased(P<0.01,P<0.05),and the duration of the increase was longer than in the hACE2-S group.Moreover,the levels of IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS in plasma were positively correlated with the degree of lung dam-age in the DM+S group.CONCLUSION In this study,the mouse model of diabetes combined with SARS-CoV-2 spike protein infection has mimicked part of the pathophysiological features of clinical patients,mainly manifested as blunted immune response and elevated HS levels with longer duration to infection alone.IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS may keep track of the course of disease in patients with diabetes combined with SARS-CoV-2 infection.

Ebselen (EbSe) is a synthetic lipo-soluble selenium-containing organic small molecule compound with a wide range of physiological and pharmacological activities. EbSe is one of the most well-studied selenium-containing compounds. Early studies have shown that EbSe possess various bio-activities by eliminating intracellular oxygen free radicals and inhibiting lipid peroxidation. Recent studies have demonstrated that the multifarious biological activities of EbSe based on its selenium effect on the cysteine residues of substrates. Its potential clinical application range keeps expanding, which has a prospect application in the treatment of multiple system diseases in the human body. In addition, the latest study confirmed that EbSe has outstanding antibacterial activity against multidrug-resistant bacteria infections. Based on this, this article briefly reviews the research progress of pharmacological activities and related clinical applications of EbSe, providing some references for scientific research and clinical workers.

Objective The aims of this study were to analyze the clinical characteristics and laboratory test results of stageⅣ lung cancer patients with Pulmonary thromboembolism(PTE),and to find out the risk factors for pulmonary thromboembolism. Methods A total of 70 patients with stage IV lung cancer were selected from the First Affiliated Hospital of Nan Chang University from January 2011 to October 2017. Blood routine,blood biochemistry,coagulation function,tumor markers(CEA,CA199,CA125, NSE,Cyfra211)and multi-slice spiral CT pulmonary angiography(CTPA)were collected in these patients. Univariate analysis was applied to compare the clinical features and laboratory tests between PTE and non-PTE groups. Multivariate logistic regression analy-sis was applied to explore significant risk factors of PTE. Results Univariate analysis showed that serum albumin,blood leukocyte, neutrophil percentage,increased Cyfra211 and abnormal tumor markers were risk factors for PTE in patients with stage IV lung canc-er. Multivariate logistic regression analysis showed that the number of abnormal tumor markers ≥4(OR=7. 016,95% CI:1. 916 ~25. 686)was an independent risk factor for PTE in stage IV lung cancer. Conclusion The number of abnormal tumor markers is an independent risk factor for pulmonary thromboembolism in stageⅣlung cancer. When the number of abnormal tumor markers is≥4, it is necessary to highly alert the possibility of stage IV lung cancer with pulmonary thromboembolism.

Objective To investigate the CT features of early infection stage of thoracic and pulmonary paragonimiasis. Methods Medical records of 56 patients with thoracic and pulmonary paragonimiasis from January 2010 to June 2017 were collected, and the patients were diagnosed and treated at Yongjia County People's Hospital, and the results of laboratory examination and CT imaging features were analyzed retrospectively. Results The absolute value of eosinophils in peripheral blood of 56 patients was (5.61 ± 3.18) × 109/L, and the percentage of eosinophils was (35.90 ± 19.16)％, all of which increased to varying degrees. Forty-two patients had different degrees of pleural effusion and 52 cases with lung lesions. Lung lesions demonstrated one or several kinds of foci at the same time, randomly distributed in the lung field, mostly located in the sub-pleural lung tissue. There were 12 cases with pulmonary ground glass shadow, 4 cases with peribronchitis, 31 cases with pulmonary invasive lesions and 28 cases with pulmonary nodular/strip shadow. The size of most nodules were 0.5 - 1.0 cm, accompanied with halo sign. Conclusions The CT features of early infection stage of thoracic and pulmonary paragonimiasis are diverse. The size of 0.5 - 1.0 cm lung nodules with halo sign has certain characteristics in the diagnosis of paragonimiasis. Peribronchitis, infiltrative lesions, pleural effusion and increased peripheral blood eosinophil percentage can suggest diagnosis.

Objective To explore the effect of timeliness motivation theory-based continuing care on the self-care ability and healthy behavior in elderly patients with type 2 diabetes. Methods A total of 202 elderly patients with type 2 diabetes in our hospital were selected,and were randomly divided into observation group and control group according to the random number table, with 101 cases in each group. The control group were given healthy related education during hospitalization , and post-discharge telephone follow-up every month, lasting 10~15min each time.The observation group were additionally given timeliness motivation theory-based continuing care by telephone follow-up each month , including emotional arousal , need motivation , examples stimulating and benefit motivation, lasting 6 months. Their self-care ability and healthy behavior in the two groups were compared. Result The self-care ability in the observation group was significantly significantly better than that of the control group (P<0.001), and had significantly much more healthy behaviors than the latter (P < 0.001). Conclusion Timeliness motivation theory-based continuing care can improve the self-care ability and healthy behavior in elderly patients with type 2 diabetes.

To investigate the CT appearances in early stage of clustering lung paragonimiasis,9 cases of two clustering lung paragonimiasis caused by eating raw stone-crab and laboratory examination were included in the study.Eight cases consulted by doctors in the hospital and their appearances were retrospectively analyzed.There were pleural effusion of varying degree (n=8) and random distribution sub-pleural pulmonary infiltrative lesions (n=7).The accompany appearances of the latter had lunar halo sign,characteristic tunnel sign (n=1) and peri-bronchitis (n=1).If CT detects pulmonary infiltrative lesions of random distribution within sub-pleura or tunnel sign,combining with the history of eating raw stone crabs and other freshwater fishes,with the rise of eosinophilic granulocytes in peripheral blood,the diagnosis of paragonimiasis should be suggested.