Objective:To explore the association between cumulative blood pressure (BP) and the risk of cerebrovascular disease (CVD) in older adults.Methods:This retrospective cohort study consecutively selected 4 480 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2009 as the study subjects. The cumulative BP was calculated using the area under the curve from measurements taken at baseline (2008-2009), the first follow-up (2011), and the second follow-up (2014). The subjects were grouped with the quartiles (Q1-Q4) of cumulative systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The Cox proportional hazards regression models were used to analyze the hazard ratios (HR) and 95% CI for the association between cumulative BP and the risk of CVD among older adults. The restricted cubic spline function was employed to examine the potential dose-response pattern between cumulative BP and the risk of CVD. Results:During a total of 40 230 person-years of follow-up, with a mean follow-up duration of (8.98±2.16) years, 768 new cases of CVD were identified. The older adults in the highest quartile (Q4) of cumulative SBP, DBP, and PP had a significantly higher risk of CVD compared to those in the lowest quartile (Q1), with a HR of 1.68 (95% CI: 1.36-2.06), 1.67 (95% CI: 1.36-2.06), and 1.52 (95% CI: 1.24-1.84), respectively (all P<0.001). For every 10 mmHg (1 mmHg=0.133 kPa)×year increase in cumulative SBP, DBP, and PP, the risk of CVD increased by 2% ( HR=1.02, 95% CI: 1.01-1.03), 3% ( HR=1.03, 95% CI: 1.01-1.05), and 2% ( HR=1.02, 95% CI: 1.01-1.03), respectively (all P<0.05). The restricted cubic spline model revealed a linear positive correlation between cumulative SBP, DBP, and PP with the risk of CVD among older adults (all P for nonlinearity>0.05). When cumulative SBP, DBP, and PP exceeded 791.9 mmHg×years, 462.9 mmHg×years, and 323.6 mmHg×years, corresponding to an average BP level of 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively, the risk of CVD began to increase. Conclusions:Elevated long-term cumulative BP may increase the risk of CVD in older adults. Caution is warranted when SBP, DBP, and PP exceed 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively.

Objective:To explore the association between cumulative blood pressure (BP) and the risk of cerebrovascular disease (CVD) in older adults.Methods:This retrospective cohort study consecutively selected 4 480 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2009 as the study subjects. The cumulative BP was calculated using the area under the curve from measurements taken at baseline (2008-2009), the first follow-up (2011), and the second follow-up (2014). The subjects were grouped with the quartiles (Q1-Q4) of cumulative systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The Cox proportional hazards regression models were used to analyze the hazard ratios (HR) and 95% CI for the association between cumulative BP and the risk of CVD among older adults. The restricted cubic spline function was employed to examine the potential dose-response pattern between cumulative BP and the risk of CVD. Results:During a total of 40 230 person-years of follow-up, with a mean follow-up duration of (8.98±2.16) years, 768 new cases of CVD were identified. The older adults in the highest quartile (Q4) of cumulative SBP, DBP, and PP had a significantly higher risk of CVD compared to those in the lowest quartile (Q1), with a HR of 1.68 (95% CI: 1.36-2.06), 1.67 (95% CI: 1.36-2.06), and 1.52 (95% CI: 1.24-1.84), respectively (all P<0.001). For every 10 mmHg (1 mmHg=0.133 kPa)×year increase in cumulative SBP, DBP, and PP, the risk of CVD increased by 2% ( HR=1.02, 95% CI: 1.01-1.03), 3% ( HR=1.03, 95% CI: 1.01-1.05), and 2% ( HR=1.02, 95% CI: 1.01-1.03), respectively (all P<0.05). The restricted cubic spline model revealed a linear positive correlation between cumulative SBP, DBP, and PP with the risk of CVD among older adults (all P for nonlinearity>0.05). When cumulative SBP, DBP, and PP exceeded 791.9 mmHg×years, 462.9 mmHg×years, and 323.6 mmHg×years, corresponding to an average BP level of 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively, the risk of CVD began to increase. Conclusions:Elevated long-term cumulative BP may increase the risk of CVD in older adults. Caution is warranted when SBP, DBP, and PP exceed 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively.

Vascular cognitive impairment(VCI)is a group of syndromes ranging from mild cognitive impairment to dementia caused by cerebrovascular disease,due to the lack of sensitivity and specific biomarkers,it is difficult to identify and diagnose early.Abnormal connectivity is observed in brain regions of patients with vascular cognitive disorders,locates mainly in the default mode network(DMN),and changes in their abnormal functional connectivity correlated with the degree of patients' cognitive impairment.Resting-state functional magnetic resonance imaging(rs-fMRI)is a commonly used method to detect the internal activity of the brain at resting state.The use of various rs-fMRI to study abnormal changes in the DMN in patients with VCI is useful to further investigate the pathogenesis of VCI and provide an objective basis for imaging.This article mainly reviews the application of rs-fMRI in the DMN in patients with VCI,bringing new perspectives for the correct diagnosis and assessment of VCI.

Objective:To explore the practical effects of achieving transformative learning in students based on the "case-based+problem-oriented" teaching method for the course of "orthopedic rehabilitation".Methods:A "case-based+problem-oriented" method was introduced in clinical courses for students in the rehabilitation therapy program at Tianjin Medical University. The students in the class were randomly divided into the "case-based+problem-oriented" teaching group (56 students) and the traditional teaching group (57 students). This study compared students' exam scores for different types of theoretical questions at the end of the semester. A self-filled anonymous questionnaire survey was conducted to evaluate the effectiveness of transformative learning, including the understanding of rehabilitation theory, learning interest, doctor-patient communication ability, disease analysis and judgment ability, and rehabilitation practice ability. SPSS 20.0 was used for t test and χ2 text. Results:The "case-based+problem-oriented" teaching group achieved significantly higher scores in various types of questions and total scores compared with the traditional teaching group [(85.67±4.78) vs. (72.98±6.49), t=8.78, P=0.004)]. Students in the "case-based+problem-oriented" teaching group showed higher interest in transformative learning and a considerably increased awareness of knowledge acquisition and innovative transformation. Students in the "case-based+problem-oriented" teaching group demonstrated higher abilities in theoretical learning, communication, disease exploration, and analytical judgment in this major and course. Conclusions:The "case-based+problem-oriented" clinical transformative teaching method integrates the theoretical teaching, clinical thinking, and medical training, promotes the students' enthusiasm for learning, and improves their proactive learning of knowledge and ability to transform and innovate.

Objective To investigate the effect and potential mechanism of early exercise intervention on cerebral myelin in cerebral ischemia rats.Methods A total of 18 SD rats were randomly divided into the sham group,the middle cerebral artery occlusion resting group(MCAO-SED)and the middle cerebral artery occlusion exercise group(MCAO-EX),with 6 rats in each group.Except the sham group,the middle cerebral artery occlusion model was prepared by modified Longa line embolization method in other groups.After modeling,rats in the MCAO-EX group were placed on a treadmill for exercise intervention for 28 days.Neurological function was assessed by modified neural function deficit score(mNSS).Infarct volume was detected by MRI scanning(T2),myelin basic protein(MBP)expression was detected by immunofluorescence.Myelin sheath structure was detected by transmission electron microscopy.Western blot assay was used to detect endoplasmic reticulum stress-related protein expression.Apoptosis was detected by TUNEL staining.Results After 28 days of intervention,compared with the MCAO-SED group,the nerve function recovered well in the MCAO-EX group,infarct volume decreased,myelin integrity increased,MBP fluorescence intensity expression increased and MBP expression level increased.The expression levels of ATF6,p-IRE1,p-PERK and cleaved caspase 3 were significantly decreased,and apoptosis was reduced.Conclusion Early exercise can inhibit endoplasmic reticulum stress-induced apoptosis,promote cerebral myelin repair,reduce infarct size and improve nerve function.

Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on the hemodynamics of the cerebral cortex after an ischemic stroke using functional near-infrared spectroscopy (fNIRS).Methods:Twenty-six ischemic stroke survivors with upper limb motor dysfunction were assigned at random to an experimental group ( n=17) or a control group ( n=9). Both groups received conventional rehabilitation training, but the experimental group additionally received 20 minutes of rTMS at 10Hz applied over the supplementary motor area (SMA) of the affected side. The treatment was applied 5 times a week for 3 weeks. The control group received sham rTMS stimulation on the same schedule. Before and after the intervention, the motor function of the hemiplegic upper limb was evaluated in both groups using the Fugl-Meyer upper extremity assessment (FMA-UE). The concentration of oxyhemoglobin (HbO) in the primary sensorimotor cortex (SM1), the SMA and the premotor cortex (PMC) was measured using fNIRS. The FMA-UE scores were then tested for any significant correlation with the HbO concentrations. Results:After the intervention, the average FMA-UE scores had increased significantly in both groups, with significantly greater improvement in the experimental group. Among the experimental group a significant increase was also observed in the HbO concentration in channel 20 during the preparation period and in channel 31 during the task period, along with a significant decrease in it in the CL-SM1 and CL-(SMA+ PMC) during the task period. HbO concentration in channel 31 during the task period before the intervention was found to be significantly correlated with the changes in the experimental group′s FMA-UE scores.Conclusions:High-frequency rTMS of the SMA on the affected side can improve the motor functioning of a hemiplegic upper limb, promote activation of the local motor cortex on the lesioned side, and inhibit activation of the contralateral motor cortex. HbO concentration in channel 31 may predict these therapeutic effects.

Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on the hemodynamics of the cerebral cortex after an ischemic stroke using functional near-infrared spectroscopy (fNIRS).Methods:Twenty-six ischemic stroke survivors with upper limb motor dysfunction were assigned at random to an experimental group ( n=17) or a control group ( n=9). Both groups received conventional rehabilitation training, but the experimental group additionally received 20 minutes of rTMS at 10Hz applied over the supplementary motor area (SMA) of the affected side. The treatment was applied 5 times a week for 3 weeks. The control group received sham rTMS stimulation on the same schedule. Before and after the intervention, the motor function of the hemiplegic upper limb was evaluated in both groups using the Fugl-Meyer upper extremity assessment (FMA-UE). The concentration of oxyhemoglobin (HbO) in the primary sensorimotor cortex (SM1), the SMA and the premotor cortex (PMC) was measured using fNIRS. The FMA-UE scores were then tested for any significant correlation with the HbO concentrations. Results:After the intervention, the average FMA-UE scores had increased significantly in both groups, with significantly greater improvement in the experimental group. Among the experimental group a significant increase was also observed in the HbO concentration in channel 20 during the preparation period and in channel 31 during the task period, along with a significant decrease in it in the CL-SM1 and CL-(SMA+ PMC) during the task period. HbO concentration in channel 31 during the task period before the intervention was found to be significantly correlated with the changes in the experimental group′s FMA-UE scores.Conclusions:High-frequency rTMS of the SMA on the affected side can improve the motor functioning of a hemiplegic upper limb, promote activation of the local motor cortex on the lesioned side, and inhibit activation of the contralateral motor cortex. HbO concentration in channel 31 may predict these therapeutic effects.

Objective:To explore any effect of intermittent hypoxia (IH) on myocardial energy metabolism and its mechanism.Methods:Twenty-one male Sprague-Dawley rats were randomly divided into a sham operation group, a myocardial infarction group and an observation group. The latter two groups received occlusion of the left anterior descending coronary artery. The observation group then lived in an hypoxic environment intermittently for 4 hours/day, 5 days/week for four weeks, while the other 2 groups were exposed to a normal level of oxygen. The ejection fraction of the left ventricle (LVEF) was measured at 1 week after the modeling and 4 weeks after the start of the intervention. Also at that point myocardial fibrosis, mitochondrial structure, ATP content, and the protein expressions of adenosine monophosphate-activated protein kinase alpha1 (AMPKα1) and sirtuins protein family member 3 (SIRT3) were assessed in all three groups.Results:A significant decrease in the LVEF, the number of mitochondria, ATP content, AMPKα1 and SIRT3 protein were observed in the infarction group compared with the sham group. There was also a significant increase in the myocardial fibrosis index. Moreover, the LVEF decreased significantly and the myocardial fibrosis index had increased significantly in the observation group compared with the sham operation group, though the two groups exhibited no significant differences the number of mitochondria, ATP content, or the expression of AMPKα1 or SIRT3. Compared with the myocardial infarction group, in the observation group there was a significant increase in the LVEF, the number of mitochondria, ATP content, and the expression of AMPKα1 and SIRT3 protein, with a significant decrease in the fibrosis index. AMPKα1 and SIRT3 level were positively inter-correlated and positively correlated with LVEF and ATP content.Conclusions:IH intervention can promote ATP synthesis and improve mitochondrial structure by regulating the AMPKα1/SIRT3 pathway, reducing myocardial fibrosis and enhancing cardiac function.

Human Gasdermin B (GSDMB) gene, as a member of the Gasdermin (GSDM) gene family, may be associated with the development of asthma, tumor and immune system diseases. Recent studies have found that cell pyroptosis can be mediated by GSDMB protein. The N-terminus of GSDMB cleaved by Granzyme A (GZMA), which is secreted by cytotoxic lymphocytes, can directly promote cell pyroptosis. Moreover, GSDMB protein promotes the cleavage of Gasdermin D (GSDMD) by binding to cysteinyl aspartate specific proteinase-4 (caspase-4), thus indirectly promoting cell pyroptosis. This article summarized the progress in the mechanism of GSDMB gene-mediated cell pyroptosis and the related diseases.

Objective:To observe the effect of early exercise intervention on the corticospinal tract of rats with cerebral infarction.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sedentary group (SED), a 1 day later exercise group (1D) and a 1 week later exercise group (1W), each of 6. A modified Longa′s method was used to occlude the middle cerebral artery to model a stroke. Rats in the 1D and 1W groups started exercising 1 day and 1 week after the modeling, while those in the sedentary group were placed on a stationary treadmill for 30 minutes every day. Modified neurological severity scores (mNSSs) were used to quantify neurological functioning after 1, 4 and 8 weeks. Magnetic resonance imaging was used to calculate the infarct volume ratio, and diffusion tensor imaging was used to detect the fractional anisotropy ratio (rFA) of the corticospinal tract for correlation with the mNSS scores. The corticospinal cord′s morphology was observed using DTT.Results:After 1 week the average mNSS score of the 1D group was significantly lower than the other two groups′ averages. At 4 weeks the average mNSS scores of both the 1D and the 1W group were significantly lower than the sedentary group′s average. At 8 weeks the 1D group′s average mNSS score was significantly lower than those of the other two groups, while that of the 1W group was significantly lower than the sedentary group′s average. At 1 and 4 weeks after modeling the average infarct volume ratio in the 1D group was significantly lower than those of the other groups. By 4 weeks the average infarct volume ratio of the 1W group was significantly lower than that of the sedentary group, and by 8 weeks the average infarct volume ratios of both the 1D and 1W groups was significantly lower than that of the sedentary group. After 1 week the average rFA of the 1D group was significantly lower than that of the sedentary group, but by 4 weeks the averages of the 1D group and the 1W group were both significantly higher than the sedentary group′s average. At 8 weeks the 1D group′s average rFA was significantly above that of the 1W group and of the sedentary group, and that of the 1W group was significantly higher than that of the sedentary group. After 8 weeks the corticospinal tracts in the 1D group appeared to be more symmetrical than those of the other 2 groups. The rFA results correlated strongly with the mNSS scores ( r=-0.707). Conclusions:Exercise can promote corticospinal cord remodeling and improve neurological function after cerebral infarction, at least in rats. It should be started as early as possible.