ObjectiveTo obtain a construct chimeric antigen receptor macrophages （CAR-M） targeting disialoganglioside GD2 （GD2） and harboring the intracellular domain of macrophage-specific activating signaling adaptor protein DNAX-activating protein 12 （DAP12）. MethodsA CAR molecule targeting GD2 with the DAP12 intracellular domain as the signaling module ［Anti-GD2 CAR （DAP12）］ was designed， synthesized， and cloned into an adenoviral vector. This virus was used to infect PMA-differentiated THP-1 macrophages to construct green fluorescent protein （GFP）-labeled Anti-GD2 CAR THP-1 cells. CAR expression was confirmed using live-cell imaging. In vitro co-culture assays were performed to evaluate the phagocytic function of empty， Anti-GD2 CAR-M （CD3ζ）， and Anti-GD2 CAR-M （DAP12） groups against glioma cells with high （T98G） and low （U251） GD2 expression. ResultsThe CAR adenovirus efficiently transduced THP-1 macrophages， resulting in successful generation of Anti-GD2 CAR-M. Flow cytometry analysis following co-culture with glioma cells showed that compared to the empty group， the Anti-GD2 CAR-M （CD3ζ） group exhibited significantly enhanced phagocytosis （P<0.05）. Furthermore， compared to the Anti-GD2 CAR-M （CD3ζ） group， the Anti-GD2 CAR-M （DAP12） group demonstrated a further increase in phagocytic capacity specifically against GD2-high T98G cells （P<0.05）. ConclusionAnti-GD2 CAR-M （DAP12） cells are successfully established by transducing PMA-differentiated THP-1-M with recombinant Anti-GD2 CAR （DAP12） adenovirus. The engineered CAR-M can specifically target phagocytose glioma cells with high GD2 expression.

ObjectiveTo obtain stably transfected chimeric antigen receptor macrophages （CAR-M） targeting disialosylganglioside （GD2） based on the constitutive expression of myeloid differentiation factor 88 （MYD88）. MethodsAn Anti-GD2 CAR adenoviral vector incorporating the CD3ζ （cluster of differentiation 3 zeta chain）-MYD88 fusion construct was designed and constructed. THP-1-derived macrophages （THP-1M）， induced by phorbol 12-myristate 13-acetate （PMA） differentiation， were infected with this adenovirus to generate Anti-GD2 CAR THP-1 cells bearing a green fluorescent protein （GFP） tag. CAR expression was monitored using a live-cell imaging system. The phagocytic function of Empty CAR-M， Anti-GD2 CAR-M（CD3ζ）， and Anti-GD2 CAR-M（CD3ζ-MYD88） groups against glioma cells was evaluated in vitro through co-culture experiments， and their polarization status was also analyzed. ResultsCAR adenovirus successfully transfected THP-1 to obtain Anti-GD2 CAR-M. After co-culture with glioma cells， flow cytometry results showed that compared with the Empty CAR-M group and the Anti-GD2 CAR-M（CD3ζ） group， the Anti-GD2 CAR-M（CD3ζ-MYD88） group exhibited enhanced phagocytosis against T98G cells with high GD2 expression （P<0.05） and also showed upregulation of CD86 （P<0.05）. Compared with the Empty CAR-M group and the Anti-GD2 CAR-M（CD3ζ） group， the Anti-GD2 CAR-M（CD3ζ-MYD88）CAR-M group exhibited enhanced phagocytosis against T98G cells with high GD2 expression （P<0.05） and also showed upregulation of CD86 （P<0.05）， and the expression of inflammatory cytokines interleukin （IL）-6 and IL-12 was increased in this group （P<0.05）. ConclusionThis study successfully constructed Anti-GD2 CAR-M cells and verified their phagocytic activity， demonstrating that constitutive expression of MYD88 can promote inflammatory polarization of CAR-M. This provides a potential structural modification approach for the development of pro-inflammatory CAR-M.

Objective To explore the effects of different daily doses of methadone maintenance treatment(MMT)on subjective craving and brain function under drug cues among heroin addicts,providing an objective basis for the formulation of methadone medi-cation plan in clinical practice.Methods Twenty-nine heroin addicts were included and grouped according to the daily dose of metha-done 40 mg,≤40 mg/d group 15 participants(group A),>40 mg/d group 14 participants(group B).The functional magnetic reso-nance imaging(fMRI)data of brain response induced by drug cues were collected using a 3.0T MR scanner,and the craving data induced by drug cues in the subjects were collected.Brain activity and behavioral data processing were analyzed using SPM8 and SPSS 20.0 software.Results There were no statistically significant differences in craving scores between the two groups of subjects exposed to drug cues(t=-0.69,P>0.05).The brain regions with differences in brain response included the left caudate nucleus(group A showed signifi-cantly enhanced response),and the strength of its response was negatively correlated with the daily dose of methadone(r=-0.465,P=0.025).Conclusion Higher doses of MMT may help control the value cognitive processing of drug cues in heroin addicts through the caudate nucleus,which can better prevent relapse.In the future,the degree of activation of the caudate nucleus under drug cues may serve as an indicator for evaluating the effectiveness of methadone treatment.

Objective To investigate the association between healthy lifestyle factors and cardiovascular biological aging,as well as the relative contributions of different lifestyle factors.Methods Based on the clinical biochemical data and anthropometric data from the baseline survey of the UK Biobank(UKB),the Klemera-Doubal method(KDM)was used to establish cardiovascular biological age(CBA),and CBA acceleration was calculated accordingly.Multiple linear regression models were used to estimate the associations between healthy lifestyle factors and CBA acceleration.Then,the Quantile g-computation(QGC)was applied to evaluate the relative contributions of different lifestyle factors to CBA acceleration,with further analyses conducted separately for male and female populations.Additionally,stratified analyses were performed based on age,sex,body mass index(BMI),racial background,and family history of cardiovascular diseases to examine population heterogeneity.Results A total of 251 478 participants were included in the study.Both the overall healthy lifestyle score and each of the 7 lifestyle factors were negatively associated with CBA acceleration(overall lifestyle score:β=-0.75,95%CI:-0.77 to-0.73).Regarding the relative contributions of different lifestyle factors,alcohol consumption and diet accounted for the highest proportions(25.8%and 25.7%,respectively).However,there were differences by sex—alcohol consumption contributed the most in men(29.5%),followed by diet(23.0%),while in women,diet contributed the most(34.5%)and alcohol consumption accounted for a relatively low proportion(5.5%).Stratified analyses suggested that sex,BMI,and race might be potential effect modifiers.Conclusion Lifestyle factors,as modifiable behaviors,can slow the rate of cardiovascular biological aging.Among these factors,alcohol consumption and diet may represent effective targets for intervention.

Objective To explore the effects of different daily doses of methadone maintenance treatment(MMT)on subjective craving and brain function under drug cues among heroin addicts,providing an objective basis for the formulation of methadone medi-cation plan in clinical practice.Methods Twenty-nine heroin addicts were included and grouped according to the daily dose of metha-done 40 mg,≤40 mg/d group 15 participants(group A),>40 mg/d group 14 participants(group B).The functional magnetic reso-nance imaging(fMRI)data of brain response induced by drug cues were collected using a 3.0T MR scanner,and the craving data induced by drug cues in the subjects were collected.Brain activity and behavioral data processing were analyzed using SPM8 and SPSS 20.0 software.Results There were no statistically significant differences in craving scores between the two groups of subjects exposed to drug cues(t=-0.69,P>0.05).The brain regions with differences in brain response included the left caudate nucleus(group A showed signifi-cantly enhanced response),and the strength of its response was negatively correlated with the daily dose of methadone(r=-0.465,P=0.025).Conclusion Higher doses of MMT may help control the value cognitive processing of drug cues in heroin addicts through the caudate nucleus,which can better prevent relapse.In the future,the degree of activation of the caudate nucleus under drug cues may serve as an indicator for evaluating the effectiveness of methadone treatment.

Objective Based on the scoping review framework,we collected cancer-related cognitive impairment(CRCI)assessment tools from home and abroad to provide references for the standardized use of such assessment tools.Methods Chinese and English databases,such as Pubmed,Embase,Web of Science Core Collection database,CNIK,Wanfang database,and VIP database,were systematically searched from the establishment of the database to April 12,2024,to extract the basic information of evaluation tools,and the search results were standardized.Results 31 articles were included,of which 26 were about the development or validation of assessment tools,and 5 were about the localization and application of assessment tools,involving 19 subjective assessment tools and 8 objective assessment tools.Most of the subjective assessment tool reliability and validity tests were internal consistency reliability tests and concurrent validity tests;14 subjective assessment tools were multidimensional scales;6 objective assessment tools measured retest reliability;4 were unidimensional measures.Conclusion The assessment tools chosen for the current studies vary.It is recommended to choose the evaluation tools and judgment standards recommended by the International Cognitive and Cancer Working Group to carry out relevant research.In the future,the existing CRCI assessment tools should be further verified and improved,and a localized CRCI assessment tool should be continuously introduced or developed.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.