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 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 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 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.

To examine the risk factors for developing diabetes on its 3-year outcome in an elderly population with impaired fasting glucose (IFG). We selected the 328 elderly with impaired fasting glucose in Binhai new area of Tianjin as the research object. All subjects participated in objective examinations such as physical activity ability tests, blood tests and anthropometric examinations, and completed the questionnaire survey. Between baseline and 3-year outcome, 56 of the subjects with IFG at baseline have developed diabetes. After multivariate adjustments, we found that higher incidence of diabetes was associated with higher fasting plasma glucose (OR=9.30, 95%CI 2.84-30.48, P<0.01) and reduced grip strength/weight (OR=0.88, 95%CI 0.82-0.94, P<0.01). Moreover, the combination of higher fasting plasma glucose and lower grip strength/weight would lead to higher incidence of diabetes compared with higher fasting plasma glucose or lower grip strength/weight alone (P<0.05). In this study, high fasting plasma glucose and low muscle strength were associated with blood glucose worsening in three years in IFG patients. In addition to blood glucose levels, physical activity is also a risk factor for diabetes in older adults.

INTRODUCTIONThis study aims to assess whether cryosurgery is a feasible local therapy for bone metastatic prostate cancer (bmPCa).

METHODSA total of 23 patients with bmPCa who received cryosurgery and adjuvant androgen deprivation therapy (ADT) were included in the cryosurgery group (Group 1). Another 23 matched patients who received only ADT served as the control (Group 2). Prostate-specific antigen (PSA) nadir level, time to PSA nadir, time to castration-resistant prostate cancer (CRPC), progression-free survival and therapy response of bone metastases were compared between the groups.

RESULTSThe median follow-up time in Group 1 and Group 2 patients was 37 (range 19-53) months and 42 (range 24-56) months, respectively. Patients in Group 1 had fewer local complications, lower PSA nadir level (0.23 ng/mL vs. 4.01 ng/mL; p = 0.024), shorter median time to PSA nadir (3 months vs. 7 months; p < 0.001), longer median time to CRPC (36 months vs. 27 months; p = 0.002) and longer progression-free survival (35 months vs. 26 months; p = 0.003) compared to those in Group 2. Therapy responses of bone metastases were similar in the two treatment groups (p = 0.689).

CONCLUSIONCryosurgery is a feasible local therapy for bmPCa patients with prostate volume less than 50 mL and without bulk tumours outside the prostate capsula. Cryosurgery may decrease PSA nadir level, local complications and time to PSA nadir, delay time to CRPC and improve progression-free survival.

Objective To investigate the therapeutic efficacy of the combined therapy of daoyin prescription and cognitive training on vascular dementia(VD).Methods Totally 75 patients with VD were randomly divided into 3 treatment groups:daoyin prescription,cognitive training and two combined treatments(n =25 each) for 3 months.Mini mental state examination(MMSE),Loewenstein occupational therapy cognitive assessment(LOTCA)and activities of daily living scale(ADL)were used for assessing therapeutic efficacy among three treatment groups.Results There were no significant differences in baseline clinical data among the three groups (P ＞ 0.05),possessing data comparability.Scores of MMSE,LOTCA,ADL and LOTCA subitems of orientation,visual perception,spatial perception,visual movement,thinking operation and attention were significantly improved in the 3 groups after 3 months intervention versus pre-treatment with three treatments(all P＜0.01).There were significant differences in scores of MMSE,LOTCA,ADL and LOTCA subitems of orientation,visual perception,visuo-motor organization and attention between combination therapy group versus daoyin prescription group and cognitive training group (all P ＜ 0.05).Conclusions Combined treatments of daoyin prescription and cognitive training have better effect on vascular cognitive function in patients with and VD.It can markedly improve the activities of daily living and cognitive function.It is worthy of further research in clinical medicine.

Objective: To establish an HPLC-fluorescence detection method for the determination of thioguanosine-monophosphate (TGMP), thioguanosine-diphosphate (TGDP) and thioguanosine-triphosphate (TGTP) in red blood cells (RBC), as well as quantify the individual thioguanine nucleotides metabolites in kidney transplant recipients with azathioprine (AZA) therapy.Methods: The individual thioguanosine phosphates were extracted from RBC by dichloromethane and subsequently oxidized by potassium permanganate.The separation was achieved on a Nucleosil C18 column (150 mm×4.6 mm,5 μm) with an ion pairing reagent and detected by a fluorescence detector (excitation at 315 nm, emission at 390 nm).The mobile phase consisted of 20 mmol·L-1 potassium phosphate buffer (pH was adjusted to 6.8 by 5 mmol·L-1 tetrabutylammonium hydrogensulfate)-acetonitril (80:20) with the flow rate of 1.0 ml·min-1.Results: TGMP, TGDP and TGTP were quantified from RBC within the range of 50-500, 50-1000 and 100-5 000 pmol·ml-1, respectively.The limit of quantification (LOQ) was 50, 50 and 100 pmol·ml-1 RBC for TGMP, TGDP and TGTP, respectively.The intra-and inter-day RSDs were below 7.0% with the method recovery between 95.0% and 103.6%.The mean extraction recovery was above 90%.The assay was applied in the blood samples of 30 kidney transplant recipients with AZA therapy, and the results indicated that TGTP was the predominant phosphate metabolite in RBC.Conclusion: The method is simple, rapid, sensitive and specific, and it can quantitatively determine the individual thioguanosine phosphates in RBC of kidney transplant recipients with AZA therapy.