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.

Objective·To investigate the effects of the cancer-testis antigen 14(CT14)on embryonic and larval development in nematodes by using the model organism Caenorhabditis elegans(C.elegans),aiming to uncover its potential functions and mechanisms during development.Methods·Transgenic C.elegans strains were constructed by using microinjection for the inducible expression of human CT14(HsCT14),a truncated mutant of CT14(HsCT14?CIR)lacking CT14-specific intermediate region(CIR),and a green fluorescent protein(GFP)control.The impacts of full-length and truncated mutant CT14 on nematode embryonic and larval development were analyzed and compared.Additionally,transgenic C.elegans strains with inducible expression of CT14 from various primates,including the crab-eating macaque(Macaca fascicularis)and mouse lemur(Microcebus murinus),were also constructed to assess the effects on egg hatching and larval-to-adult transformation rates.The differential gene expression in nematode embryos induced by CT14 was analyzed by Smart-seq transcriptome sequencing,with further insights gained through KEGG(Kyoto Encyclopedia of Genes and Genomes)and GSEA(Gene Set Enrichment Analysis),to explore the involved biological processes and pathways.Results·The induced expression of HsCT14 and its truncated mutant HsCT14?CIR significantly reduced the hatching rate of nematode eggs,with a more pronounced effect observed in HsCT14-expressing strains.Differential interference contrast(DIC)microscopy imaging revealed significant morphological abnormalities in embryos expressing HsCT14 during the comma stage.Nematodes expressing HsCT14 or HsCT14?CIR exhibited developmental arrest in larvae and substantially lower larval-to-adult transformation rates compared to the GFP control.The impact was more pronounced in nematodes expressing HsCT14 than those with HsCT14?CIR.The expression of Macaca fascicularis CT14(MfCT14)exhibited significant effects on the hatching rate and adult transformation rate,similar to that of HsCT14,while the expression of Microcebus murinus CT14(MmCT14)displayed significantly reduced impact compared to HsCT14 and MfCT14.Smart-seq results indicated that CT14 expression affected various biological processes in nematode embryos,related to ATP-dependent chromatin remodeling and DNA replication.Conclusion·Ectopic expression of the cancer-testis antigen CT14 significantly disrupts both embryonic and larval developments in C.elegans,with the CIR sequence substantially enhancing this effect.It suggests that CT14 may play an important regulatory role in biological development by affecting gene expression in multiple pathways,including chromatin remodeling.

Objective: To investigate cardiovascular disease (CVD) prevention status among residents with intra-urban migration in Central China, so as to provide insights into targeted prevention and control of CVD. Methods: Basic data of residents aged 35 to 75 years who participated in Early Screening and Comprehensive Intervention Project for CVD high-risk populations in Central China from September 2015 to August 2020 were collected. According to birth place, type of registered residence and current residence, residents were divided into four groups: local residents in old urban area, local residents in new urban area, other urban migrants and other rural migrants. The status of CVD primary and secondary prevention, were analysed by using a robust Poisson regression model. Results: A total of 76 513 residents were recruited, including 29 420 males (38.45%) and 47 093 females (61.55%), and had a mean age of (56.36±9.84) years. There were 45 087 (58.93%) local residents in old urban area, 23 868 (31.19%) local residents in new urban area, 5 668 (7.41%) other urban migrants and 1 890 (2.47%) other rural migrants. After adjusting for variables such as age, gender and educational level, the results of robust Poisson regression analysis showed that compared with local residents in old urban area, local residents in new urban area had lower compliance rates of non- or moderate-drinking (RR=0.987, 95%CI: 0.975-1.000) and healthy diet (RR=0.535, 95%CI: 0.365-0.782), lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.616, 95%CI: 0.511-0.741), lower awareness (RR=0.873, 95%CI: 0.782-0.974) and control rates (RR=0.730, 95%CI: 0.627-0.849) of hypertension; other urban migrants had higher compliance rate of non-smoking (RR=1.045, 95%CI: 1.017-1.075); other rural migrants had lower proportion of using aspirin as primary prevention in CVD high-risk population (RR=0.826, 95%CI: 0.707-0.966). Conclusion The CVD primaryprevention among local residents in new urban area is relatively poor among four groups of residents in Central China, and key interventions are needed.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

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.