This study aimed to investigate the effects of fusion proteins GnRH-GRP(G3G6)and HSP65-STEAP1(HST1)on dendritic cells(DC)and the sensitization of DCs to B16F10 melanoma. The fusion proteins G3G6 and HST1 were obtained using the previous engineering strains in our laboratory. Group by unsensitized DC(US-DC), the G3G6 fusion protein sensitized DC, the HST1 fusion protein sensitized DC(HST1-DC)and the combined sensitized DC(GH-DC), the mouse bone marrow-derived DCs were sensitized with fusion protein to obtain the fusion protein sensitized DC vaccines. B16F10 melanoma cells were transplanted into C57BL/6J male mice to construct a melanoma model(1×106 cells per mouse), and DC vaccine was injected for treatment. The antitumor efficacy of DC vaccine was explored by in vitro and in vivo experiments. Flow cytometry analysis showed that the fusion protein can effectively stimulate DC into differentiation and maturation; in the animal experiment, the inhibition rate of melanoma treated with G3G6-DC was 35. 75%, that of HST1-DC group and combination group were 34. 03% and 55. 74%. It was initially proved that both G3G6-DC and HST1-DC can effectively inhibit the growth of transplanted tumors of melanoma B16F10 cells in mice, and the combination therapy is superior to the single therapy.

AIM:To investigate the effects of proteasome inhibitor MG 132 on the expression of SnoN in renal tubule epithelial cells incubated in high glucose , and to explore the possible mechanism and function that MG 132 reduces or slows down renal tubular interstitial injury after incubated in high glucose .METHODS:The NRK-52E cells were divid-ed into normal control group (NG), high glucose group (HG) and high glucose plus pretreatment with different doses of MG132 group (HG+MG132).The immunofluorescence staining was used to detect the protein expression of E-cadherin and α-smooth muscle actin (α-SMA) in NRK-52E cells under different conditions .The relative protein expression levels of SnoN, Smad ubiquitination regulatory factor 2 (Smurf2), Arkadia, E-cadherin, α-SMA and collagen type Ⅰ(Col-Ⅰ) were detected by Western blotting .RESULTS:Compared with NG group , the expression of E-cadherin and SnoN was de-creased (P<0.05), while the expression of α-SMA, Col-Ⅰ, Smurf2 and Arkadia was increased (P<0.05).Compared with HG group, the protein expression of SnoN and E-cadherin was significantly up-regulated in HG+MG132 group ( P<0.05 ) , and the protein expression of α-SMA and Col-Ⅰwas significantly down-regulated in a dose-depended manner ( P<0.05).However, no effect on the protein expression of Smurf2 and Arkadia was observed.CONCLUSION: MG132 in-hibits the degradation of SnoN protein induced by high glucose , thus reducing the renal fibrosis .

Objective To discuss the importance of data coding standards for the application of information technology , and put forward a method to solve the identification of complex medical materials in database structure design .Methods utilization of standardized coding , establishment of coding rules and a series of basic data dictionary , improvement of property fields and association dictionaries were used to regulate the generation , collection and processing of information , and to establish data standards for military medicine warehouse management information system .Results The design and implementation of data standards could be applicable for a variety of databases .Conclusion The establishment of standards and regulations of the data were critical to system design , develop-ment, implementation and even the successful operation , especially in management information systems , which had complex manage-ment form including property management , administration, and packaging assembly management .

OBJECTIVE：To provide evidence-ba sed evidence for clinical treatment and decision by evaluating efficacy ，safety and cost-effectiveness of denosumab in the treatment of giant cell tumor of bone （GCTB）. METHODS ：Retrieved from PubMed ， the Cochrane Library ，ScienceDirect，CNKI，Wanfang database and VIP as well as health technology assessment （HTA）organi- zation websites ，HTA reports ，randomized controlled trials （RCTs），single-arm trials and retrospective studies were included about denosumab in the treatment of GCTB in the adults and adolescents with mature bone ，and their qualities were evaluated. HTA reports were analyzed with descriptive analysis qualitatively ；Meta-analysis was conducted for single-arm clinical studies and retrospective studies by using R version 3.6.0 software. RESULTS ：Among 49 screened literatures ，there were 6 HTA reports ，5 single-arm trials and 3 retrospective studies ．No eligible RCTs were retrieved. HTA reports of various countries generally believed that denosumab possessed good efficacy and safety ；HTA reports of France ，Austrila and other contries showed that denosumab possessed economics. For the GCTB patients who was unresectable ，denosumab would bring the clinical benefits to about 81％ [95％CI（77％，86％）] of patients. The complete response rate and partial response rate was around 14％[95％CI（10％，19％）] and 51％[95％CI（32％，70％）]，respectively. For the GCTB patients was resectable ，denosumab would prevent some patients from receiving surgery （35％）[95％CI（21％，49％）] or bring surgical down staging to them （40％）[95％CI（36％，45％）]，the postoperative recurrence rate after experiencing the denosumab therapy was about 19％[95％CI（7％，35％）]，and median relapse time was approximately 6.73 months [ 95％CI（3.92，9.55）] after receiving surgery. Main grade 3-4 or high frequercy ADR requiring treatment was back pain ，limbs pain ，hypophosphatemia and jaw osteonecrosis. CONCLUSIONS ：Based on the currently available evidence，among the studies and regions covered in this study ，denosumab has favorable efficacy ，safety and cost-effectiveness in the treatment of TCTB.

AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.

Myocardial fibrosis is featured by excessive proliferation of cardiac fibroblast and collagen deposition. There is close relationship between myocardial fibrosis and various cardiovascular disease, and it is potential risk factor for sudden death. At present the precise mechanism remains unclear.Myocardial fibrosis has been found to relate with renin-angiotensin-aldosterone system,cell factor,oxidative stress,inflamatory factor,endothelial function obstacles,Intracellular calcium ion. These factors influences the occurrence of myocardial fibrosis by the same or different pathway.

Objective:To investigate the distribution law of TCM syndrome types and the differences in influencing factors among different syndrome types in unstable angina pectoris (UA), so as to provide an objective basis for TCM syndrome differentiation and treatment of UA.Methods:A retrospective study chose 1 684 inpatients in the Department of Cardiovascular Medicine of the First Affiliated Hospital of Henan University of Chinese Medicine from August 2015 to April 2019. Epidata 3.0 software was used to input general information of patients [gender, age, length of hospital stay, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP)], laboratory indicators[TC, TG, HDL-C, LDL-C, fibrinogen (FIB), thrombin time (TT), D-dimer (D-dimer), HbA1c], TCM syndrome types (qi and yin deficiency syndrome, phlegm turbidity and obstruction syndrome, qi deficiency and blood stasis syndrome, heart blood stasis syndrome, qi stagnation and blood stasis syndrome, heart and kidney yang deficiency syndrome) and other information. A database was established to analyze the distribution of TCM syndrome types and the relationship with the general information of patients, blood lipids, blood sugar and coagulation indexes. Logistic regression was used to analyze the influencing factors of different syndrome types.Results:The distribution of syndrome types in 1 684 UA patients was as follows: qi and yin deficiency syndrome (44.7%), phlegm turbidity and obstruction syndrome (35.3%), qi deficiency and blood stasis syndrome (7.4%), heart blood stasis syndrome (5.3%), qi stagnation and blood stasis syndrome (4.6%), heart and kidney yang deficiency syndrome (2.6%); more men than women ( P<0.05); there were significant differences in the distribution of gender, age, BMI, TC, and HDL-C among the 6 syndrome types ( P<0.05); the age of patients with phlegm turbidity and obstruction syndrome was younger than that of qi and yin deficiency syndrome and heart blood stasis syndrome ( P<0.05); the age of patients with qi stagnation and blood stasis syndrome was younger than that of qi and yin deficiency syndrome, heart blood stasis syndrome, and heart kidney yang deficiency syndrome ( P<0.05); BMI of patients with phlegm turbidity and obstruction syndrome was higher than that of qi and yin deficiency syndrome and qi stagnation and blood stasis syndrome ( P<0.05); the level of TC in patients with phlegm turbidity and obstruction syndrome was lower than that of qi and yin deficiency syndrome and qi deficiency and blood stasis syndrome ( P<0.05); the level of HDL in patients with qi and yin deficiency syndrome was lower than that in qi deficiency and blood stasis syndrome and qi stagnation and blood stasis syndrome. Binary Logistic regression analysis found that TC [ OR(95% CI)=0.761(0.592, 0.978)] and HDL-C [ OR(95% CI)=2.131(1.145, 3.966)] were independent influencing factors for predicting qi deficiency and blood stasis syndrome ( P<0.05); age[ OR(95% CI)=1.017 (1.008, 1.026)], length of hospital stay [ OR(95% CI)=1.019 (1.001, 1.038)], DBP [ OR(95% CI)=0.984(0.975, 0.993)] and HDL-C [ OR(95% CI)=0.984(0.975, 0.993)] were independent influencing factors for predicting qi and yin deficiency syndrome ( P<0.05); age [ OR(95% CI)=0.965 (0.946, 0.985)], and HDL-C [ OR(95% CI)=2.329(1.206, 4.500)] were independent influencing factors for predicting qi stagnation and blood stasis syndrome ( P<0.05); age [ OR(95% CI)=0.982 (0.973, 0.991)], length of hospital stay [ OR(95% CI)= 0.978 (0.958, 0.997)], BMI [ OR(95% CI)=1.048 (1.015, 1.082)], DBP [ OR(95% CI)=1.014 (1.004, 1.024)] and HDL-C [ OR(95% CI)=0.505 (0.351, 0.726)] were independent influencing factors for predicting phlegm turbidity and obstruction syndrome ( P<0.05); age [ OR(95% CI)=1.031(1.003, 1.060)] and DBP [ OR(95% CI)=1.028(1.001, 1.056)] were independent influencing factors for predicting heart kidney yang deficiency syndrome ( P<0.05). Conclusion:The distribution of TCM syndrome types in UA shows a certain regularity, among which qi and yin deficiency syndrome and phlegm turbidity and obstruction syndrome are more common. Gender, age, BMI, TC, HDL-C are different among TCM syndrome types, which can provide some reference for UA TCM syndrome differentiation and treatment.

OBJECTIVE：To systematically evaluate the pharmacoeconomic research of the second-generation direct-acting antiviral agents （DAAs）in the treatment of hepatitis C ，and to provide methodological suggestions for economic research ，and to provide decision-making reference for the adjustment of medical insurance catalogues and market access. METHODS ：Retrieved from PubMed ，EMbase，the Cochrane library ，CNKI，Wanfang database and VIP ，the pharmacoeconomic researches of the second-generation DAAs for hepatitis C were collected during Jan. 2015-Jan. 2020. The quality of included studies were evaluated with the checklist about Consolidated Health Economics Evaluation Reporting Standards （CHEERS），and the data were extracted and analyzed quantitatively. RESULTS ：A total of 14 studies were included ，and the standard coincidence rate ranged from 79.2％ to 95.8％；the overall quality was relatively high. Thirteen （92.9％）studies had compared the economics of different treatment schemes from the perspective of the payer by using the Markov model and the lifetime study time limit. Compared with the second-generation DAAs treatment schemes based on sofosbuvir ，all the research results showed that Ombitasvir combined with Dasabuvir（3D），EBR/GZR and GLE/PIB were more economical in the target countries ；single factor sensitivity analysis showed that the research results were more sensitive to the three parameters of drug price ，drug SVR rate and health status utility value. CONCLUSIONS：Among the second-generation DAAs for hepatitis C ，the three regimens of 3D，EBR/GZR and GLE/PIB are more economical. It is recommended that future research on the economics of medicines for hepatitis C adopted dynamic model and the research perspective of the whole society to carry out direct high-quality economic research on a variety of DAAs ；at the same time，considered the effects of drug price ，drug SVR rate and health status utility value on the robustness of basic analysis results in sensitivity analysis in order to increase the credibility of the research results.

Objective To explore the neuroprotective effect of targeted regulation Nrf2 gene on rats with brain injury caused by acute severe carbon monoxide ( CO ) poisoning. Methods A total of 180 healthy adult SD rats were divided into 4 groups at random:normal control group( NC group) ,CO poisoning group(CO group),lentivirus group(LV group) and Nrf2 gene therapy group(Nrf2 group),and 45 rats in each group. An acute CO toxic rat model was established by inhalation in a hyperbaric oxygen tank. The lentivirus group was directly injected with lentivirus dilution (4×106 TU/μl) into striatum with a microsy-ringe guided by a stereotactic apparatus,and the Nrf2 gene therapy group was administrated the same dose of recombinant Nrf2 gene lentivirus dilution,while rats in the normal control group and the CO poisoning group were received the same amount of normal saline. Five rats were taken and decapitated at day 1,day 7 and week 2 from each group,respectively. The mitochondrial membrane potential (MMP) of neurons in brain tis-sue was detected by JC-1 method,and the expressions of Nrf2 and GCLC proteins were observed by immuno-histochemistry and Western Blot. Results Compared with the NC group (cortex:(75. 3±6. 8);hippocam-pus:(76. 4±7. 1);striatum:(73. 8±7. 3)) at the same time point,the MMPs of neurons in CO group (cor-tex:(34. 5±6. 7);hippocampus:(30. 3±5. 6);striatum:(41. 5±6. 1) and LV group (cortex:(36. 8±6. 2);hippocampus:(30. 8±6. 0);striatum:(42. 7±6. 3)) were significantly decreased,and the difference was sig-nificant(P<0. 05). However,there was no significant difference between the CO poisoning group and the lentivirus group (P>0. 05). A small amount of Nrf2 protein (0. 22±0. 05) and GCLC protein (0. 24±0. 04) were expressed in the brain tissue of normal control rats. The expressions of Nrf2 protein (0. 31±0. 06,0. 31 ±0. 05) and GCLC protein (0. 30±0. 04,0. 31±0. 07) in CO group and LV group were slightly increased (P<0. 05). Similarly,there was no significant difference between the CO poisoning group and the lentivirus group (P>0. 05). The MMPs value of nerve cells in the Nrf2 group (cortex:(53. 3±5. 3);hippocampus:(56. 9±6. 1);striatum:(60. 6±6. 0)) also decreased,but it was significantly higher than that in the CO group and the LV group at the same time point (P<0. 05) . The expression of Nrf2 in brain tissue was signifi-cantly increased (0. 59±0. 05),and there was significant difference between CO group and LV group at the same time point (P<0. 05);GCLC protein increased slightly (0. 37±0. 06),but there was no statistical difference compared with CO poisoning group and lentivirus group (P>0. 05). Conclusion CO poisoning could induce oxidative stress and damage mitochondrial function of nerve cells. The active state of targeted regulation Nrf2 could significantly enhance the antioxidant capacity of rats and positively protect rats against brain injury induced by acute severe CO poisoning.

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.