Objective To investigate the role of B7/CD28 costimulation pathway blockade with adenovirus-mediated CTLA4-Ig gene in macrophage and CD8~+T cell infiltration and cell apoptosis in murine liver transplantation. Methods Rat pairs were divided into three groups: SD-to-Wistar transplantation control group, CsA-treated group and CTLA4-Ig-treated group. IHC and TUNEL were used to analyze the expression of CTLA4-Ig gene in liver and immune cells infiltrate and cell apoptosis in liver grafts. Pathology was done on all harvested grafts. ResultsCTLA4-Ig gene expression was positive in the donor liver on day 7 after administering adenovirus-mediated CTLA4-Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of immune cells in CTLA4-Ig-treated group was less than that in rejection control group. the apoptotic index of rejection group on day 3,5,7 was significantly higher than those of CTLA4-Ig-treated. Conclusions CTLA4-Ig gene was constantly expressed in the donor liver after single intravenousely injection into rats using adenovirus as vector. Adenovirus-mediated CTLA4-Ig gene therapy can inhibit infiltration of immune cells and apoptosis in grafts, thus prolonging the survival of recipients.

To evaluate the medication for one patient with the infection by carbapenem-resistant escherichia coli (CRE) to provide reference for the treatment of drug-resistance bacteria in clinical practice. During the development of anti-infective treatment regimen, clinical pharmacists analyzed and evaluated the situation, and provided suggestions for the medication:amikacin combined with fosfomycin and tigecycline. Physician adopted the recommendations,and the infective symptoms obtained a better control. The participation of clinical pharmacists in the treatment of intractable infection practice can provide reasonable and effective medication recommendations for clinics to improve anti-infective effectiveness in clinics.

OBJECTIVE：To evaluate the economic value of dapagliflozin combined with metformin in the treatment of type 2 diabetes mellitus （T2DM）. METHODS ：Based on related literatures and phase 3 randomized controlled clinical trial （RCT）of metformin alone or combined with dapagliflozin for T2DM，Markov model was built to simulate the dynamic changes of 3 schemes such as 5 mg dapagliflozin combined with metformin ，10 mg dapagliflozin combined with metformin or metformin alone （the dose of metformin were all 1 500 mg）in the treatment of T 2DM patients without or with complications and death . Quality adjusted life years（QALYs）was used as a health output indicator and the threshold of willingness-to-pay was 3 times of GDP in 2019. Cohort simulation in Markov model was applied to obtain long-term effect and cost of 3 schemes in the treatment of T 2DM. The incremental cost-effectiveness ratio （ICER）was analyzed ；the sensitivity of cost ，utility and discount was analyzed to check the stability of the analysis result. RESULTS ：According to the results of Markov model cohort simulation ，after 10 years of disease progression，compared with metformin alone ，ICER of 5 mg dapagliflozin combined with metformin was 41 259.17 yuan/QALYs， and that of 10 mg dapagliflozin combined with metformin was 92 824.85 yuan/QALYs. Compared with 5 mg dapagliflozin combined with metformin ，ICER of 10 mg dapagliflozin combined with metformin was 1 209 525.95 yuan/QALYs. Extension of termination time to 20 or 30 years had no effect on results. According to the sensitivity analysis ，the change of key parameters in the set range did not affect the model results ，indicating the result was stable. CONCLUSIONS ：For T 2DM，5 mg dapagliflozin combined with metformin is more cost-effective .

OBJECTIVE To evaluate the cost-effectiveness of omalizumab in the treatment of severe allergic asthma from the perspective of healthcare providers in China. METHODS Based on the data from an international multicenter study of omalizumab in the treatment of severe allergic asthma， the Markov model was constructed according to the progression of severe allergic asthma， with a cycle of 4 weeks. Long-term health outcomes and costs of omalizumab combined with standard of care（SoC） regimen versus SoC regimen in the treatment of severe allergic asthma were simulated by using quality-adjusted life years （QALYs） and incremental cost-effectiveness ratio（ICER） as output indexes. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were performed to test the robustness of the results. RESULTS Compared with the SoC regimen， ICER for the omalizumab combined with SoC regimen was 107 723.05 yuan/QALY， which was less than the willingness-to-pay（WTP） threshold （268 074 yuan/QALY） calculated by three times per capita gross domestic product（GDP） in China in 2023. The one-way sensitivity analysis showed that the baseline serum level of immunoglobulin E had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the omalizumab+SoC regimen had a 93.00% probability of being cost- effective. The scenario analysis showed that in the real world， the billing method of omalizumab based on specifications rather than actual usage may increase ICER. CONCLUSIONS Compared with the SoC regimen， the combination of omalizumab and SoC regimen for treating severe allergic asthma is cost-effective， with a WTP threshold of three times China’s per capita GDP