Traumatic brain injury (TBI) involves both primary mechanical damage and refractory secondary injuries, resulting in high disability rate and poor prognosis. Current therapeutic strategies for TBI include surgical intervention, neuroprotective agents, moderate hypothermia therapy and spinal cord stimulation. However, most of these therapeutic approaches primarily address wound surface management rather than targeting specific pathogenic mechanisms underlying post-injury inflammation and neurodegenerative diseases, resulting in suboptimal efficacy. Consequently, novel therapeutic strategies targeting TBI pathological mechanisms are urgently needed. The endogenous cannabinoid system (ECS) exerts multifaceted neuroprotective effects in TBI by modulating neuroinflammation, inhibiting glutamate excitotoxicity and activating pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). Investigating the characteristics of ECS components and their related signaling pathways may yield new approaches in the development of neuroprotective drugs for TBI. Nevertheless, few ESC-targeting drugs for TBI treatment have advanced beyond preclinical or clinical trial phases. Breakthroughs in this field depend on a deeper understanding of ECS and its mechanisms in TBI. To this end, the authors reviewed researches on the composition and functions of ECS, as well as the mechanisms underlying its neuroprotective effects following TBI, aiming to provide references for the development of ECS-targeting therapies.

Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.

Objective:To explore the association of central obesity, pain, their joint effect, and interaction with frailty in middle-aged and old people in China.Methods:A total of 14 359 participants aged ≥45 years in 2011, 2013 and 2015 were selected from the China Health and Retirement Longitudinal Study to construct a cohort database. Cox proportional hazards regression models were used to estimate the association of waist-to-height ratio (WHtR) and pain with the risk for frailty. Joint effect and interaction analyses were performed.Results:In the follow-up of 77 783 person-years, frailty developed in 3 198 participants, with an incidence density of 41.11 per 1 000 person-years. Compared with the Q1 level of WHtR, its Q2, Q3 and Q4 level increased risk for frailty by 17% ( HR=1.17, 95% CI: 1.05-1.31), 24% ( HR=1.24, 95% CI: 1.11-1.40), and 43% ( HR=1.43, 95% CI: 1.25-1.63), respectively. Compared with painlessness, suffering from pain increased the risk for frailty by 97% ( HR=1.97, 95% CI: 1.83-2.11), and having 1, 2, and ≥3 pain sites increased the risk by 42% ( HR=1.42, 95% CI: 1.25-1.61), 86% ( HR=1.86, 95% CI: 1.64-2.11), and 138% ( HR=2.38, 95% CI: 2.18-2.60), respectively. The results of restricted cubic spline showed that WHtR level was associated with the risk for frailty in a J-type dose-response relationship (total P<0.001, nonlinear P<0.001), and pain quantity was positively associated with the risk in a nonlinear dose-response relationship (total P<0.001, nonlinear P<0.001). Threshold effect analysis revealed that the inflection points of WHtR and pain site number were 0.46 and 2.00, respectively ( P<0.001). Joint effect analysis showed that the Q2, Q3 and Q4 levels of WHtR combined with pain increased the risk for frailty by 146% ( HR=2.46, 95% CI: 2.11-2.87), 169% ( HR=2.69, 95% CI: 2.30-3.16), and 157% ( HR=2.57, 95% CI: 2.18-3.03). Conclusions:The risk for frailty increased with the level of WHtR and the number of pain sites in middle-aged and old people, and there was joint effect between WHtR and pain. Comprehensive management and intervention of obesity and pain are significant for the early prevention of frailty.

Objective:To explore the association of central obesity, pain, their joint effect, and interaction with frailty in middle-aged and old people in China.Methods:A total of 14 359 participants aged ≥45 years in 2011, 2013 and 2015 were selected from the China Health and Retirement Longitudinal Study to construct a cohort database. Cox proportional hazards regression models were used to estimate the association of waist-to-height ratio (WHtR) and pain with the risk for frailty. Joint effect and interaction analyses were performed.Results:In the follow-up of 77 783 person-years, frailty developed in 3 198 participants, with an incidence density of 41.11 per 1 000 person-years. Compared with the Q1 level of WHtR, its Q2, Q3 and Q4 level increased risk for frailty by 17% ( HR=1.17, 95% CI: 1.05-1.31), 24% ( HR=1.24, 95% CI: 1.11-1.40), and 43% ( HR=1.43, 95% CI: 1.25-1.63), respectively. Compared with painlessness, suffering from pain increased the risk for frailty by 97% ( HR=1.97, 95% CI: 1.83-2.11), and having 1, 2, and ≥3 pain sites increased the risk by 42% ( HR=1.42, 95% CI: 1.25-1.61), 86% ( HR=1.86, 95% CI: 1.64-2.11), and 138% ( HR=2.38, 95% CI: 2.18-2.60), respectively. The results of restricted cubic spline showed that WHtR level was associated with the risk for frailty in a J-type dose-response relationship (total P<0.001, nonlinear P<0.001), and pain quantity was positively associated with the risk in a nonlinear dose-response relationship (total P<0.001, nonlinear P<0.001). Threshold effect analysis revealed that the inflection points of WHtR and pain site number were 0.46 and 2.00, respectively ( P<0.001). Joint effect analysis showed that the Q2, Q3 and Q4 levels of WHtR combined with pain increased the risk for frailty by 146% ( HR=2.46, 95% CI: 2.11-2.87), 169% ( HR=2.69, 95% CI: 2.30-3.16), and 157% ( HR=2.57, 95% CI: 2.18-3.03). Conclusions:The risk for frailty increased with the level of WHtR and the number of pain sites in middle-aged and old people, and there was joint effect between WHtR and pain. Comprehensive management and intervention of obesity and pain are significant for the early prevention of frailty.

Objective:To explore the protocol for handgrip exercise stress echocardiography by comparing different maximal voluntary contraction（MVC）handgrip groups with bicycle exercise stress.Methods:Forty-one healthy volunteers were enrolled prospectively from June to October 2024 in Tangdu Hospital and utilized a color Doppler echocardiography system，supine cycle ergometer，and handgrip dynamometer to collect echocardiographic data at baseline，during handgrip exercises at 20%（3 min），30%（3 min），and 40%（2 min）of MVC，and spine bicycle exercise stress at peak. Parameters measured included left ventricular ejection fraction（EF），stroke volume（SV），cardiac output（CO），mitral inflow E-wave and A-wave velocities，lateral and septal mitral annular e' velocities，E/A and E/e' ratios，global longitudinal strain（GLS），left atrial reservoir strain（LAS R），conduit strain（LAS CD），and contractile strain（LAS CT）. The non-invasive myocardial work indices were also assessed，including global work index（GWI），global constructive work（GCW），global wasted work（GWW），and global work efficiency（GWE）. Statistical analyses were performed using repeated measures analysis of variance，with corrected paired t-test for comparisons between two exercise stress states. Results:Compared with the baseline state，heart rate，blood pressure，CO、GWI、GCW、GWW and LAS CT gradually increased，while EF、E/A、GLS、GWE、LAS R and LAS CD gradually decreased under 20%，30% and 40% of MVC states. The changes were most obvious at 40% of MVC state，which was selected for the handgrip exercise stress echocardiography protocol.Compared with the peak of bicycle exercise，at 40% of MVC，heart rate was significantly lower［（81.2 ± 9.7）bpm vs.（164.6 ± 11.3）bpm， P<0.05）］，systolic blood pressure was slightly lower［（152.9 ± 13.2）mmHg vs.（165.1 ± 20.4）mmHg， P<0.05］，diastolic blood pressure was higher［（96.0 ± 9.5）mmHg vs.（89.5 ± 10.9）mmHg， P<0.05］，GLS was lower［（19.1 ± 1.5）% vs.（23.5 ± 1.7）%， P<0.05］，GWI was similar［（2 254.2 ± 417.3）mmHg% vs.（2 227.5 ± 389.0）mmHg%， P>0.05］，but GWE was higher［（95.3 ± 2.0）% vs.（93.7 ± 2.0）%， P<0.05］，and LAS R was lower［（39.4 ± 4.2）% vs.（43.9 ± 4.1）%， P<0.05］. Conclusions:The 40% of MVC lasting 2 min can cause the most significant handgrip-related changes in cardiac function and can be used as the standard protocol for handgrip exercise stress echocardiography. Handgrip stress exercise can cause significant changes in cardiac systole，diastole，and work performance，showing different characteristics compared with bicycle exercise stress.

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

Objective To explore the value of inflammatory markers in predicting paroxysmal sympathetic hyperactivity(PSH)after traumatic brain injury(TBI).Methods A total of 84 TBI patients who were admitted to The Second Affiliated Hospital of Naval Medical University(Second Military Medical University)from Dec.2016 to Nov.2020 were retrospectively analyzed.They were classified into PSH group(n=41)and non-PSH group(n=43)according to whether PSH occurred during hospitalization.The baseline data and laboratory results of the 2 groups were collected and compared.Kendall correlation analysis was used to analyze the correlation between inflammatory markers and the occurrence of PSH after TBI,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of inflammatory markers to PSH.Results There were no significant differences in baseline data,including age,gender,or Glasgow coma scale score,between the 2 groups(all P＞0.05).Compared with patients in the non-PSH group,the neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune-inflammation index(SII),neutrophils and leukocytes in the PSH group were significantly increased(all P＜0.05).NLR,SII and neutrophil were positively correlated with PSH(r=0.360,0.308,0.289;all P＜0.01),with the corresponding ROC area under curve values being 0.752,0.716 and 0.702,respectively.Conclusion NLR,SII and neutrophils have a value in predicting the occurrence of PSH after TBI.

Traumatic brain injury (TBI) involves both primary mechanical damage and refractory secondary injuries, resulting in high disability rate and poor prognosis. Current therapeutic strategies for TBI include surgical intervention, neuroprotective agents, moderate hypothermia therapy and spinal cord stimulation. However, most of these therapeutic approaches primarily address wound surface management rather than targeting specific pathogenic mechanisms underlying post-injury inflammation and neurodegenerative diseases, resulting in suboptimal efficacy. Consequently, novel therapeutic strategies targeting TBI pathological mechanisms are urgently needed. The endogenous cannabinoid system (ECS) exerts multifaceted neuroprotective effects in TBI by modulating neuroinflammation, inhibiting glutamate excitotoxicity and activating pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). Investigating the characteristics of ECS components and their related signaling pathways may yield new approaches in the development of neuroprotective drugs for TBI. Nevertheless, few ESC-targeting drugs for TBI treatment have advanced beyond preclinical or clinical trial phases. Breakthroughs in this field depend on a deeper understanding of ECS and its mechanisms in TBI. To this end, the authors reviewed researches on the composition and functions of ECS, as well as the mechanisms underlying its neuroprotective effects following TBI, aiming to provide references for the development of ECS-targeting therapies.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.