eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.

OBJECTIVE To compare the anti-thymic atrophy effects of petroleum ether(PEE), ethyl acetate(EAE), n-butanol(BE) and water extract(WE) fractions from root tubers of Tetrastigma hemsleyanum Diels et. Gilg based on mice thymic atrophy model established by intraperitoneal injection of PolyI:C to preliminarily investigate the mechanisms of its effects. METHODS One hunderd ICR mice were randomly divided into 10 groups: control group, model group, low- and high-dose groups of the four extract fractions, with 10 mice in each group. The control group and model group were given equal volume of purified water and gavaged for 10 d. Starting on the 9th day, PolyI:C solution of 16 mg·kg−1 was injected intraperitoneally for 2 consecutive days, except for the control group, which was injected intraperitoneally with physiological saline. Samples of thymics were weighed and and visceral index was calculated, blood samples were taken for analysis of IL-2, TNF-α and WBC, thymic histopathology was analyzed using hematoxylin-eosin staining, Western blotting was performed to detect the expression of TNF-α, p-NF-κB and NF-κB. RESULTS Compared with the model group, all groups of extracts could enhance the thymus weight and thymus index, as well as the cortex and medulla area ratio and the number of thymic corpuscles in 1 mm2 of medulla to different degrees, and at the same time, significantly reduce the level of TNF-α in plasma, evidently inhibited the phosphorylation of NF-κB, and reduced the protein expression of TNF-α, and each of them having distinct advantages and disadvantages. Peripheral blood white blood cell, lymphocyte absolute count and lymphocyte percentage were elevated in the low-dose WE group, low-dose EAE group and high dose PEE group, IL-2 levels were significantly elevated in the low-dose WE group and high dose BE group, and these effects were particularly well demonstrated. CONCLUSION Four extracts from root tubers of Tetrastigma Hemsleyanum Diels et. Gilg can improve morphological changes and atrophy of the thymus tissue in different degrees, regulate of peripheral blood leukocyte imbalance in post-modeling mice, it may be related to the inhibition of PolyI:C-induced phosphorylation of the NF-κB and reduction of protein expression of pro-inflammatory factors.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.

Objective:It explores critical issues of discounting in health technology assessment to provide a reference for improving discount rates in China.Methods:Based on literature review and empirical cases,it compares and analyzes the practical experience of the UK and Canada and the basis for discount rate setting in pharmacoeconomic evaluation and guidelines of various countries.Results:It is found that the social time preference and social opportunity cost approach provide research perspectives for discount rate calculation.How-ever,there are differences in the choice of discounting in international guidelines and pharmacoeconomic evaluation practices,which may reflect differences among countries regarding economic environment,healthcare systems,and values.Conclusion:It calls for more basic research on discounting and suggests the formulation of discount rates that align with our China's economic environment to provide deci-sion-makers with a reliable information foundation.