ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.

Cerebral small vessel disease (CSVD) is an important cause of ischemic stroke and vascular dementia, which brings heavy burden to families and society. The prevention and treatment of CSVD has always been a research hotspot, but its pathogenesis is still not completely clear. This article reviews the pathogenesis of CSVD, including chronic cerebral hypoperfusion, blood-brain barrier dysfunction, vascular endothelial dysfunction, interstitial fluid reflux disorder, inflammatory response, and genetic factors, in order to provide more sufficient theoretical basis for early intervention and treatment of CSVD.

Cerebral small vessel disease (CSVD) refers to a series of clinical, imaging and pathological syndromes of cerebral arterioles, capillaries, venules, as well as perivascular brain parenchyma caused by various etiologies, and is one of the important causes of vascular cognitive impairment and dementia. The onset of CSVD is insidious, and the early diagnosis mainly depends on imaging examination. This article reviews the effects of different imaging markers of CSVD on cognitive function and their pathophysiological mechanism.

Objective:To investigate the clinical safety and efficacy of tirofiban in the treatment of hemiplegic stroke warning syndrome.Methods:Patients with hemiplegic stroke warning syndrome admitted to Jining First People's Hospital without receiving intravenous thrombolysis from January 2018 to May 2020 were enrolled retrospectively. Some patients were given tirofiban intravenous infusion for at least 24 h in acute phase, then received oral antiplatelet therapy (tirofiban group); some only received aspirin+ clopidogrel dual antiplatelet therapy (control group). The primary endpoint was muscle strength at the paralytic side and National Institutes of Health Stroke Scale (NIHSS) score at day 7 after onset. The secondary endpoint was the modified Rankin Scale (mRS) score at 3 months after onset, and ≤2 was defined as good clinical outcome. The safety endpoint was the bleeding events during treatment. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 30 patients with hemiplegic stroke warning syndrome were enrolled, including 19 (63.3%) in the tirofiban group and 11 (36.7%) in the control group. There was no significant difference in baseline clinical data between the two groups, and no drug-related bleeding complications occurred during treatment. The muscle strength at paralytic side and NIHSS score at day 7 after onset, NIHSS score at discharge and good clinical outcome rate at 3 months in the tirofiban group were significantly better than those in the control group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that tirofiban was an independent protective factor for good outcome after adjusting the NIHSS score at the beginning of treatment (odds ratio 0.040, 95% confidence interval 0.040-0.449; P=0.009). Conclusions:Tirofiban is safe and effective in the treatment of patients with hemiplegic stroke warning syndrome in acute phase. It can effectively block the progress of the disease, improve the outcome of patients, and will not increase the risk of bleeding.

Thalamus plays an important role in the connection of sensory, motor and cognitive functions between multiple subcortical regions and cerebral cortex. In recent years, the important role of thalamus in cognitive function has attracted more and more attention. This article reviews the related research progress of thalamic infarction and cognitive impairment.

Objective:To investigate the safety of intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization, and explore the effect of tirofiban on perioperative thrombotic events.Methods:The clinical data of 275 patients with unruptured intracranial aneurysms who underwent stent assisted coil embolization in our hospital from January 2016 to December 2019 were retrospectively collected. Among them, 110 patients admitted to our hospital from January 2016 to December 2017 only received preoperative oral administration of aspirin and clopidogrel combined with antiplatelet treatment (classic group), and 165 patients admitted to out hospital from January 2018 to December 2019 received intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel (improved group). The differences of perioperative safety and thrombotic events between the two groups were compared and analyzed.Results:The incidence of intraoperative visual thrombotic events in the classic group and the improved group were 6.4% (7/110) and 1.2% (2/165), respectively, with significant difference ( P<0.05); the incidence of postoperative thrombotic events was 4.5% (5/110) and 2.4% (4/165), respectively, without significant difference ( P>0.05); the incidence of urethrorrhagia was 9.1% (10/110) and 21.2% (35/165), respectively, with significant difference ( P<0.05); and the incidence of gingival hemorrhage was 13.6% (15/110) and 19.4% (32/165), respectively, without significant difference ( P>0.05). No acute gastrointestinal hemorrhage or cerebral hemorrhage occurred in both groups; urethrorrhagia and gingival hemorrhage were transient and relieved spontaneously. Conclusion:Intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel can reduce the incidence of intraoperative visual thrombotic events without increasing the risk of hemorrhage in stent-assisted coil embolization of unruptured intracranial aneurysms.

Hypertension is one of the most important diseases that threaten human health, and has become a global problem. In recent years, the prevalence of hypertension in children has increased significantly year by year, and hypertension in children has a trajectory phenomenon, which is easy to cause cognitive damage and other target organ damage. Therefore, it is necessary to be alert and attached to the relationship between hypertension and cognitive impairment in children. This article reviews the epidemiological characteristics, etiology, diagnostic criteria of hypertension and pathophysiological mechanisms of cognitive impairment caused by hypertension in children.

Unruptured intracranial aneurysm (UIA) is an intracranial aneurysm without rupture history or whose wall has not completely broken through by pathological examination.In recent years,studies have found that UIA is closely associated with cognitive impairment.Understanding the relationship between UIA and cognitive impairment and the pathogenesis of cognitive impairment caused by UIA has important significance for clinical diagnosis,efficacy evaluation,and clinical intervention of UIA related cognitive disorders.This article reviews the research progress of the relationship between UIA and cognitive impairment.

Post-stroke cognitive impairment (PSCI) is one of the common complications of stroke,which has a significant impact on the life of patients.Studies have shown that the incidence of PSCI varies from region to region,and is correlated with demographic and vascular risk factors,or is significantly different due to stroke types and characteristics.The specific mechanism of PSCI remains unclear,but early identification of its risk factors is helpful for early intervention.This article reviews the risk factors of PSCI.

Objective To investigate the effect of neurotrophin-3(NT-3)on the proliferation and apoptosis of bone marrow mesenchymal stem cells(BMSCs)in rats and possible mechanisms. Methods The NT-3 overexpression and lentiviral transfection of BMSCs were co-cultured with neuronal cells respectively and then they were divided into overexpression control group,NT-3 transfection group and shRNA-NT-3 transfection group(NT-3 silencing group).MTT assay was used to detect the cell culture for 24 h,48 h and 72 h. Cell cycle and apoptosis were detected by flow cytometry for 48 h. Real-time quantitative PCR was used to detect the expression of C/EBPβmRNA.The expression of C/EBPβprotein was detected by Western blot. Results MTT results showed that the proliferation ability of BMSCs in the NT-3 overexpres-sion group was significantly higher than that in the control group(0.650±0.042,0.826±0.074)at 48 h and 72 h(P<0.05).Compared with the control group(P<0.05),the cell cycle and apoptosis of BMSCs in NT-3 silencing group were significantly decreased at 48 h and 72 h(P<0.05). The results of 48 h cell cycle and apoptosis showed that the percentage of G1 phase in BMSCs was decreased,G2 and S were increased and the apoptosis was decreased. The percentage of G1 phase in G2-S phase and the increase of apoptosis were in-creased in NT-3 silencing group. The results of Western Blot showed that C/EBPβ mRNA and protein levels were significantly up-regulated in BMSCs of NT-3 overexpression group and significantly decreased in NT-3 silencing group(P<0.05).Conclusion NT-3 may promote the expression of C/EBP beta and affect the ex-pression of its downstream target genes,which can inhibit the apoptosis of BMSCs cells.