Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To explore the effect of back-pushing manipulation on motor ability and skele-tal muscle mitochondrial function in rats with chronic fatigue syndrome(CFS).Methods Twenty-four male Sprague-Dawley rats were randomly divided into a blank group of 8 and a modeling group of 16.The CFS rat model was established using forced weight-bearing swimming combined with chronic stress stimulation for 21 days.After successful modeling,the modeling group was further divided into the modeling control(MC)group and the back-pushing manipulation(BPM)group,each of 8.In the back-pushing manipulation group,all rats were given daily 20-minute back pushing for 14 consecu-tive days after modeling.Then,all groups were recorded semi-quantitative scores of general conditions(SQS-GC),body mass,and exhaustion swimming time(EST).Moreover,the grasping ability of limbs was assessed by using the mesh screen test(MST).After the intervention,the tissue of the erector spinae muscle was taken to detect the adenosine triphosphate(ATP)content using the biochemi-cal method,and the activities of mitochondrial respiratory chain complexes Ⅰ to Ⅳ were detected by using the spectrophotometric method.Results After modeling,compared with the blank group,the SQS-GC of the MC group and BPM groups were higher(P<0.01),while EST was shorter and the MST score was lower(P<0.01 or P<0.05).However,after intervention,compared with the MC group,the SQS-GC of the BPM group was lower(P<0.01),while EST and the MST score was higher(P<0.01 or P<0.05).Compared with the blank group,the ATP content of the modelling group was significantly lower(P<0.01),and the activities of mitochondrial respiratory chain complexes I,II,III,and IV de-creased significantly(P<0.01).However,after intervention,all the above values of the BPM group in-creased significantly,compared with the MC group(P<0.01 or P<0.05).Conclusion The back-pushing manipulation can improve the mitochondrial function and energy metabolism,as well as the exercise ca-pacity,and alleviate fatigue of CFS rats,which may be related to the improvement of the activities of mitochondrial respiratory chain complexes I,II,III,and IV,and the increase of ATP content in the skeletal muscles.

Due to factors such as narrow airways and incomplete development of alveoli,newborns are prone to acute lung injury(ALI),which may progress to severe condition known as acute respiratory distress syndrome(ARDS).The mechanisms underlying the occurrence and progression of ALI in newborns involve various as-pects,including oxidative stress,iron death,inflammatory response and reduction of pulmonary surfactant.Further research into these mechanisms is expected to provide strategy to guide clinical management in novo pathway.

Objective To explore the effect of back-pushing manipulation on motor ability and skele-tal muscle mitochondrial function in rats with chronic fatigue syndrome(CFS).Methods Twenty-four male Sprague-Dawley rats were randomly divided into a blank group of 8 and a modeling group of 16.The CFS rat model was established using forced weight-bearing swimming combined with chronic stress stimulation for 21 days.After successful modeling,the modeling group was further divided into the modeling control(MC)group and the back-pushing manipulation(BPM)group,each of 8.In the back-pushing manipulation group,all rats were given daily 20-minute back pushing for 14 consecu-tive days after modeling.Then,all groups were recorded semi-quantitative scores of general conditions(SQS-GC),body mass,and exhaustion swimming time(EST).Moreover,the grasping ability of limbs was assessed by using the mesh screen test(MST).After the intervention,the tissue of the erector spinae muscle was taken to detect the adenosine triphosphate(ATP)content using the biochemi-cal method,and the activities of mitochondrial respiratory chain complexes Ⅰ to Ⅳ were detected by using the spectrophotometric method.Results After modeling,compared with the blank group,the SQS-GC of the MC group and BPM groups were higher(P<0.01),while EST was shorter and the MST score was lower(P<0.01 or P<0.05).However,after intervention,compared with the MC group,the SQS-GC of the BPM group was lower(P<0.01),while EST and the MST score was higher(P<0.01 or P<0.05).Compared with the blank group,the ATP content of the modelling group was significantly lower(P<0.01),and the activities of mitochondrial respiratory chain complexes I,II,III,and IV de-creased significantly(P<0.01).However,after intervention,all the above values of the BPM group in-creased significantly,compared with the MC group(P<0.01 or P<0.05).Conclusion The back-pushing manipulation can improve the mitochondrial function and energy metabolism,as well as the exercise ca-pacity,and alleviate fatigue of CFS rats,which may be related to the improvement of the activities of mitochondrial respiratory chain complexes I,II,III,and IV,and the increase of ATP content in the skeletal muscles.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.

Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.

Objective To investigate a convenient and quantitative solution to activation levels and functional characterization of CAR-T cells by inserting T cell activity-responsive promoter (TARP) nanoluciferase reporter gene system into a lentiviral plasmid containing the gene encoding the chimeric antigen receptor (CAR). Methods The recombinant plasmid was constructed by using whole gene synthesis and molecular cloning techniques. The lentivirus was packaged and was infected with human primary T lymphocytes. Flow cytometry was used to detected the positive rate of lentivirus-infected T cells. The functional characterization of CAR-T cells was identified by luciferase reporter gene system, Western blot, flow cytometry, and small animal live imaging techniques. Results The results of enzyme digestion identification and the plasmid sequencing showed that the recombinant plasmids were constructed, and flow cytometry displayed the normal preparation of CAR-T cells. This system could dynamically respond to the activation of CAR-T cells by luciferase reporter gene system. The functional assay in vitro confirmed that the system could reflect the exhaustion of CAR-T cells, and the small animal live imaging results demonstrated that the system can be used as a tracer of CAR-T cells in mice. Conclusion TARP nanoluciferase reporter gene system provides a more convenient, sensitive and quantitative method for evaluating CAR-T cells activation level, exhaustion phenotype and tracing.
Humans ; Animals ; Mice ; T-Lymphocytes ; Cell Line, Tumor ; Receptors, Chimeric Antigen/genetics* ; Promoter Regions, Genetic ; Immunotherapy, Adoptive/methods*

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Objective:To describe the prevalence of heart failure in China and to explore the prospective association between smoking behavior and the risk of incident heart failure.Methods:The subjects were from the China Kadoorie Biobank (CKB) and the baseline survey was conducted from June 2004 to July 2008. A total of 487 197 subjects were included in this study, after excluding those with missing BMI information, lost follow-up immediately after baseline investigation, and self-reported coronary heart disease, stroke, or malignant tumor at baseline. This study included data from baseline and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the association between smoking behavior and the risk of heart failure.Results:The median follow-up time was 10.15 years, during which a total of 4 208 new cases of heart failure occurred, with a crude incidence rate of 0.87/1 000 person-years and a cumulative incidence rate of 0.86%. The higher the age at baseline, the higher the incidence of heart failure. The incidence of heart failure in high age group, rural area and male was higher than that in low age group, urban area and female population respectively. Compared with non-smokers, there was no significant difference in the risk of heart failure in occasional smokers ( HR=1.05; 95% CI: 0.91-1.22), while former smokers ( HR=1.48; 95% CI:1.31-1.67) and current smokers ( HR=1.34;95% CI:1.22-1.49) increased risk. Former smokers ( HR=1.33;95% CI:1.21-1.46) and current smokers ( HR=1.46; 95% CI:1.31-1.64) had higher risk of heart failure than non-smokers or occasional smokers. No dose-response relationship was observed between the number of cigarettes smoked per day and the risk of heart failure in current and former smokers (for trend P=0.347 and 0.066). Compared with non-smokers or occasional smokers, the hazard ratios of <5, 5-, 10- and ≥20 years since quit smoking were 1.61 (95% CI: 1.36-1.92), 1.55 (95% CI: 1.27-1.90), 1.24 (95% CI: 1.02-1.51) and 1.35 (95% CI: 1.08-1.68), respectively (for trend P=0.091). The hazard ratios of quitting smoking due to disease and other reasons were 1.62 (95% CI:1.41-1.86) and 1.23 (95% CI: 1.04-1.45). Healthy smoking behaviors had a significant protective effect on heart failure compared with non-healthy smoking behaviors ( HR=0.75, 95% CI:0.69-0.81). Area and family history of coronary heart disease, and the smoking behaviors interacted with the risk of heart failure (for all interactions were P<0.05). Conclusions:The incidence of heart failure in China is higher in males than females, higher in rural areas than in urban areas, and increases with age. Both former smokers and current smokers had a higher risk of heart failure than nonsmokers or occasional smokers, regardless of the frequency, amount, duration, and reason for quitting. Smoking is an important risk factor for heart failure and comprehensive anti-smoking measures should be maintained.