To evaluate the immunogenicity and immunoprotective effects of a tRNA thiouridylase TgMnmA deletion strain of Toxoplasma gondii(T.gondii)on ICR mice,we constructed a mouse model immunized with RH△MnmA.Mice were immunized with 10 RH△MnmA tachyzoites by in-traperitoneal injection.After 30 d,indirect ELISA was used to detect the specific IgG antibody and its subtypes of immunized mice.Spleen lymphocyte suspension was prepared,and the splenic lym-phocyte subsets were analyzed by flow cytometry.Moreover,the relative expression level of cyto-kine mRNA was detected by real-time fluorescence quantitative PCR.After 30 d of immunization,mice were intraperitoneally inoculated with RH△ku80 tachyzoites.At 5 d post infection,the para-site load in the ascites,heart,liver and brain of mice was measured,and the survival of mice within 30 d after infection was observed and recorded.The results showed that compared with the control PBS group,RH△MnmA immunized group produced higher level of IgG and IgG2a antibodies,higher mRNA relative expression level of cytokines IL-2,IL-4,IL-6,IL-10,IL-12 and IFN-γ,and the number of CD4+and CD8a+in spleen lymphocytes also increased significantly.Mean-while,for the attack of RH△ku80 strain,the immune group can effectively reduce the parasite load in the ascites and some tissues,inhibit the reproduction of parasites In vivo,and significantly improve the survival rate of mice.The results of this study showed that the TgMnmA deletion strain of T.gondii can induce strong humoral and cellular immune responses in mice,and provide good immune protection against the infection of RHΔku80 strain,which has the potential to be-come a potentially promising live attenuated vaccine candidate against T.gondii.

As an indispensable"energy factory"within cells,mitochondria efficiently convert chemical energy from food into ATP through oxidative phosphorylation,providing continuous energy support for va-rious cellular life activities.The functional homeostasis of mitochondria maintains the cell's energy sup-ply,redox balance,cell signaling,and metabolic regulation,thereby ensuring normal cell operation and the healthy survival of organisms.Processes such as mitophagy,mitochondrial fusion and fission,mito-chondrial transport,reactive oxygen species accumulation,and calcium signaling are involved in maintai-ning mitochondrial functional homeostasis.The degeneration of dopaminergic neurons in the striatum is the main pathological feature of Parkinson's Disease(PD).Dopaminergic neurons have unique polarized and extended structures with high bioenergetic demands,making them particularly susceptible to mito-chondrial dysfunction.When mitochondrial function is impaired,the energy supply to dopaminergic neu-rons is insufficient,leading to neuronal dysfunction and subsequently triggering a series of neurodegenera-tive diseases,including PD.The molecular basis of PD pathogenesis often involves abnormalities in pro-teins that maintain mitochondrial homeostasis.These proteins play crucial roles in sustaining mitochondri-al function,and any functional abnormalities or genetic mutations can lead to mitochondrial dysfunction,thereby inducing PD.This article provides a comprehensive review of recently reported abnormalities in proteins maintaining mitochondrial function and their association with the onset and progression of PD.The aim is to gain a deeper understanding of the functions of these proteins,their genetic mutations,and their relationship with the disease,providing valuable insights for the development of effective treatments and diagnostic biomarkers for PD.

Objectives:QT interval prolongation during treadmill test exercise is one of the clinical feature of patients with long QT syndrome(LQTS).This study aimed to explore the feasibility and efficacy of treadmill exercise testing as an auxiliary diagnosis tool for LQTS in clinical practice.Methods:We enrolled normal healthy individuals,common cardiovascular disease patients,and clinically diagnosed or suspected LQTS patients,who underwent treadmill exercise test from July 2023 to July 2024 at Fuwai Hospital.A special treadmill exercise testing procedure was designed to record the QT interval correction(QTc)intervals of the twelve lead electrocardiogram at 6 time points when performing the exercise tablet,including supine,sitting,standing,peak exercise,and recovery at 1-minute and 4-minute.The differences in QTc intervals among healthy group,cardiovascular diseases group,and suspected LQTS group were compared.Results:A total of 80 cases were consecutively enrolled,including 37 normal healthy controls,25 patients with common cardiovascular disease,and 18 patients with suspected LQTS.The QTc intervals at 6 points did not differ significantly between normal healthy controls and patients with cardiovascular disease,with QTc intervals less than 480 ms at all measurement.For patients with suspected LQTS,67.7%(12/18)of these patients presented a QTc interval≥480 ms at the 4-minute during recovery period.Among them,5 cases were confirmed to have pathogenic gene mutations of LQTS by genetic testing(including 1 case with a lying electrocardiogram QTc interval of 489 ms diagnosed with LQTS 1 type and a QTc interval of 636 ms during the 4-minute recovery period after exercise);5 clinically diagnosed patients(negative or undetectable in genetic testing)with a Schwartz score≥4,and the remaining 2 patients had a Schwartz score of 3.The remaining 5/18 patients,include 2 patients with clinical Schwartz scores≥4 and 3 patients with clinical suspicion(Schwartz scores 2-3)had a 4 min QTc interval of 445-480 ms during exercise recovery.Another patient with clinical suspicion(Schwartz score 3)had a 4 min QTc interval of<445 ms during exercise recovery and a negative genetic test at a later stage.Receiver operating characteristic curve analysis showed a sensitivity of 83.3%and specificity of 98.4%for QTc interval≥482 ms during the 4-minute recovery period of exercise as the LQTS diagnostic cutoff.Conclusions:This study results suggest that this special treadmill exercise testing protocol is effective in identifying LQTS and has strong feasibility and generalizability for clinical practice.

Objective To carry out a dynamic simulation analysis on the surgical process of the surgical robot for pedicle screw placement so as to enhance the safety of the procedure.Methods Firstly,the process of pedicle screw placement were analyzed to determine the three typical force conditions during pedicle screw track drilling including no-load condition,bone layer switching condition and spine dynamic displacement condition.Secondly,a virtual protype model of the surgical robot for pedicle screw placement was constructed with the automated dynamic analysis of mechanical systems(ADAMS).Finally,the dynamic characteristics of the surgical robot were simulated and analyzed with considerations on the three typical force conditions.Results The driving torque of the robot joints was sensitive to the load applied to the end of the opener mechanism under a wide range of operating conditions.Conclusion The surgical robot meets the requirements for pedicle screw placment,and a new idea is provided for enhancing the accuracy of pedicle screw placement.[Chinese Medical Equipment Journal,2025,46(8):32-37]

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.

Objective:To study the association between subtypes of hypertension and risk for all-cause mortality and cardio-cerebrovascular mortalities in the elderly in communities of Beijing.Methods:The data were collected from the Beijing Healthy Aging Cohort Study. The elderly in 5 urban areas (former Xicheng, former Xuanwu, Fangshan, Haidian and Tongzhou) and 4 rural areas (Yanqing, Miyun, Huairou and Daxing) in Beijing were selected as the study subjects by multi-stage stratified cluster random sampling. The baseline survey was conducted from July 2009 to September 2015. The follow-up was conducted until March 31, 2021, and a total of 6 326 participants were enrolled. Cox proportional hazard regression model was used to analyze the association of SBP, DBP, normal blood pressure, high normal blood pressure, simple systolic hypertension, simple diastolic hypertension and systolic diastolic hypertension with all-cause mortality and cardio-cerebrovascular mortality.Results:By March 31, 2021, the median follow-up time was 6.30 years, the all-cause mortality density was 201.67/10 000 person-years, and the cardio-cerebrovascular mortality density was 90.20/10 000 person-years. Multivariate Cox proportional hazard regression model analysis showed that the risk for all-cause mortality increased by 5.6% ( HR=1.056, 95% CI: 1.020-1.092), and the risk for cardio-cerebrovasculvar mortality increased by 12.5% ( HR=1.125, 95% CI: 1.071-1.182) for every 10 mmHg increase in SBP. The risk for all-cause mortality increased by 8.6% ( HR=1.086, 95% CI: 1.023-1.152), and the risk for cardio-cerebrovascular mortality increased by 19.9% ( HR=1.199, 95% CI: 1.101-1.306) for every 10 mmHg increase in DBP. Compared with the normal blood pressure group, the risk for all-cause mortality increased by 64.8% ( HR=1.648, 95% CI: 1.049-2.591) and the risk for cardio- cerebrovascular mortality increased by 112.8% ( HR=2.128, 95% CI: 1.069-4.233) in the simple diastolic hypertension group. The risk for all-cause mortality increased by 34.4% ( HR=1.344, 95% CI: 1.023-1.467) and the risk for cardio-cerebrovascular mortality increased by 111.3% ( HR=2.113, 95% CI: 1.384-3.225) in the systolic-diastolic hypertension group. Conclusions:In the elderly in communities of Beijing, beside systolic-diastolic hypertension. It is necessary to pay close attention to the simple diastolic hypertension, which has lower prevalence, and give targeted prevention and treatment.

Objective:To investigate the association of urinary albumin-to-creatinine ratio (UACR) in normal range and cardiovascular health (CVH) score with cardio-cerebroascular and all-cause mortality in urban elderly residents in Beijing.Methods:Based on Beijing Healthy Aging Cohort Study, data from 1 817 elderly participants with normal UACR were analyzed, and UACR was used as both continuous and categorical variable. "Life's Essential 8" was used to develop a CVH score. Statistical analysis was performed by using software SPSS 26.0 and R 4.2.1, including two independent samples t-test, χ2 test and non-parametric test. Multivariable Cox proportional hazard regression models stratified by CVH score and the restricted cubic spline were used to analyse the association of UACR with the risk for cardio-cerebrovascular and all-cause mortality. Results:By March 31, 2021, the median follow-up time M ( Q1, Q3) was 11.28 (10.84, 11.36) years, a total of 308 deaths were recorded during follow-up, and the mortality density was 163.87/10 000 person-years. The age of the participants was (71.4±6.6) years, and 1 070 participants were women. The results showed that the risk for both cardio-cerebrovascular disease and all-cause mortality decreased with the decrease of UACR in the low CVH score group ( HR=0.500, 95% CI: 0.341-0.734; HR=0.793, 95% CI: 0.647-0.971), and in the high CVH score group, there was a decreasing trend in the risk for cardio-cerebrovascular mortality with the decrease of UACR ( HR=0.665, 95% CI: 0.447-0.990). Compared with the participants with low CVH score and higher UACR, the risk for cardio-cerebrovascular and all-cause mortality decreased by 68.9% and 45.6%, respectively, in the participants with high CVH score and lower UACR ( HR=0.311, 95% CI: 0.131-0.739; HR=0.544, 95% CI: 0.360-0.822), and the risk for all-cause mortality decreased by 26.7% in the participants with high CVH score and higher UACR ( HR=0.733, 95% CI: 0.542-0.993). Conclusions:In urban elderly residents in Beijing, higher UACR were associated with a significantly increased risk for cardio-cerebrovascular and all-cause mortality, and in the low-CVH score group, decreased UACR was protective factor against cardio-cerebrovascular and all-cause mortality. The combined effect of cardiovascular health status and normal UACR had a greater protection against the risk for cardio-cerebrovascular and all-cause mortality.

Objective:To describe and analyze the distribution characteristics of a body shape index (ABSI) and its association with all-cause mortality in the elderly in communities of Beijing.Methods:The baseline and follow-up data of 10 423 subjects in Beijing Healthy Aging Cohort Study were used. The endpoint outcome was all-cause mortality in follow-up. The associations of ABSI, BMI and waist circumference with all-cause mortality were analyzed with a Cox proportional hazard regression model.Results:The mean follow-up time in this cohort was 6.36 years and the all-cause mortality was 15.27%. The restricted cubic spline results showed that ABSI showed a "U" association with all-cause mortality in the total population. After adjustment for confounding factors, compared with the normal ABSI group, the risk for all-cause mortality was higher in the low ABSI group ( HR=1.69, 95% CI: 1.32-2.17) and high ABSI group ( HR=1.75, 95% CI: 1.40-2.18). Compared with the normal BMI group, low BMI was associated with an increased risk for all-cause mortality ( HR=1.70, 95% CI: 1.40-2.08). Compared with the normal waist circumference group, central obesity was associated with a decreased risk for all-cause mortality ( HR=0.89, 95% CI: 0.80-0.99). The results of gender specific analysis on ABSI association with all-cause mortality were similar to that in total population, but the strength of association varied among different age groups. Cross-grouping results showed that older people with normal BMI and waist circumference and abnormal ABSI had an increased risk of all-cause mortality ( HR=1.91, 95% CI: 1.22-2.99). Conclusions:In Beijing, ABSI is correlated with the risk for all-cause mortality in the elderly population, which is more sensitive and specific than the traditional indicators (BMI and waist circumference). They can be used as one of the physical measurement indicators for all-cause mortality risk prediction in the health risk assessment and management in the elderly.

Objective:To explore the association between physical activity (PA) level and all-cause mortality in the elderly with different obesity status in Beijing.Methods:The study subjects were from the Cardiovascular and Cognitive Healthy Study in Middle-Aged and Elderly Residents of Beijing, a total of 3 746 individuals aged ≥60 years in the baseline survey between 2013 and 2015 were included in the study. Questionnaire survey and physical examination were conducted to collect the basic information of the individuals. The metabolic equivalent of the elderly was used to calculate the PA level, and an international PA questionnaire was used to determine the PA intensity. BMI, waist-to-height ratio (WHtR) and a body shape index (ABSI) were used to evaluate individuals' obesity status. The distribution of different PA levels under different obesity states was described by using bar chart and cumulative percentage bar chart. Cox proportional hazard regression model was used to analyze the correlation between the level of PA and all-cause mortality risk in different types of obesity status.Results:By December 31, 2019, the median follow-up time was 5.46 years, and the mortality density was 244.55/10 000 person-years. Compared with the individuals in high-PA intensity group, the all-cause mortality risk increased by 41% ( HR=1.41, 95% CI: 1.14-1.76) and 122% ( HR=2.22, 95% CI: 1.76-2.81), respectively, in moderate and low PA intensity groups. Compared with the individuals in high-PA intensity-high-obesity group, based on the BMI, the all-cause mortality risk increased by 85% ( HR=1.85, 95% CI: 1.08-3.16) and 250% ( HR=3.50, 95% CI: 2.01-6.10) in those in moderate-PA intensity-high-obesity group and in low-intensity-high-obesity group. Based on the WHtR, the all-cause mortality risk increased by 53% ( HR=1.53, 95% CI: 1.02-2.29) and 218% ( HR=3.18, 95% CI: 2.09-4.86), respectively, in those with moderate-PA intensity-high-obesity and those with low-PA intensity-high-obesity. According to the ABSI, the all-cause mortality risk increased by 120% in those in low-PA intensity-high-obesity group ( HR=2.20, 95% CI: 1.53-3.18). Based on any one of the indicators BMI, WHtR, or ABSI, there was no significant difference in all-cause mortality risk between high-intensity-moderate-obesity group and high-intensity-low-obesity group (all P>0.05). Conclusions:PA level is closely associated with the all-cause mortality risk in the elderly in communities of Beijing. Increasing PA level can not only reduce the all-cause mortality risk but also reduce even eliminate the excess all-cause mortality risk associated with obesity.

Objective:To analyze the association between different lipid indicators and cardio-cerebrovascular mortality in the elderly, identify a better lipid indicator for the risk for cardio-cerebrovascular mortality in the elderly in communities of Beijing.Methods:The elderly aged 60 years and above were selected from the Beijing Healthy Aging Cohort Study from July 2009 to September 2015. Remnant cholesterol (RC) was derived by calculation. The Cox proportional hazard regression models determined the HR and 95% CI incidating the associations of baseline different lipid indicators with cardio-cerebrovascular and all-cause mortality. Results:By March 31, 2021, with a mean follow-up duration of 6.88 years in the study population, a total of 492 cardio-cerebrovascular deaths and 1 056 all-cause deaths wre recorded. The HR values indicating the association between LDL-C, HDL-C, and RC were 0.87 (95% CI: 0.78-0.97), 0.46 (95% CI: 0.35-0.62), and 1.29 (95% CI: 1.14-1.45) for cardio-cerebrovascular mortality, respectively, and 0.93 (95% CI: 0.86-1.00), 0.66 (95% CI: 0.55-0.80) and 1.22 (95% CI: 1.12-1.33) for all-cause mortality. The associations of RC and HDL-C with cardio-cerebrovascular mortality were consistent regardless of hyperlipidemia in the elderly. Subgroup analyses showed that elevated RC was associated with increased risk for cardio-cerebrovascular mortality, and elevated HDL-C was associated with decreased risk for cardio-cerebrovascular mortality in the elderly in different gender, age, smoking status, drinking status, and diabetes status groups in communities of Beijing. Conclusion:RC might be a better potential lipid indicator for the risk for cardio-cerebrovascular mortality in the elderly in communities compared with traditional cholesterol indicator.