Objective:To investigate the risk of new-onset stroke caused by cerebral microbleed (CMB) and asymptomatic lacunar infarction (ALI) and their risk factors.Methods:A prospective observational study over a 18 month period was conducted on 397 non stroke patients who visited the Affiliated Hospital of Xuzhou Medical University from March 2020 to June 2022. By the presence of CMB and ALI about magnetic resonance imaging, they were divided into th control group (without CMB and ALI, 117 cases, 29.5%), ALI group (101 cases, 25.4%), CMB group (89 cases, 22.4%) and CMB-ALI group (90 cases, 22.7%).They were followed up for 18 months, the risk factors for CMB, ALI, and the risk of new stroke were analyzed.Results:The systolic blood pressure and uric acid in the CMB group were higher than those in the control group: (155.2 ± 24.2) mmHg(1 mmHg = 0.133 kPa) vs. (138.2 ± 19.0) mmHg, (387.0 ± 28.3) μmol/L vs. (354.0 ± 21.5) μmol/L, there were statistical differences ( P<0.05). After followed up for 18 months, the incidence rate of cerebral infarction, cerebral hemorrhage and TIA in the CMB group and CMB-ALI group were higher than those in the control group: 13.5%(12/89), 13.3%(12/90) vs.5.1%(6/117); 9.0%(8/89), 10.0%(9/90) vs. 2.6%(3/117); 5.6%(5/89), 6.7%(6/90) vs. 0.8%(1/117), there were statistical differences ( P<0.05). Conclusions:CMB is prone to abnormal systolic blood pressure and uric acid. CMB, CMB-ALI are prone to new onset ischemic stroke, cerebral hemorrhage and TIA.

Objective:To investigate the risk factors of post-stroke depression (PSD) in patients with first acute stroke 6 months after onset.Methods:Three hundred and sixty-seven patients with acute stroke who were treated for the first time in the Affiliated Hospital of Xuzhou Medical University were selected retrospectively. After onset for 6 months, the patients were followed up and divided into PSD group and non-PSD group. The clinical data, blood index, imaging data, degree of nerve damage and the patient's stigma level were compared between the two groups.Results:Totally 182 and 185 cases were included in the PSD and non-PSD groups, respectively. The incidence of PSD at 6 months post-stroke was 49.6% (182/367). The results of univariate analysis showed that diseased region, drinking history, monthly income, standard of culture, serum cortisol, total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Stigma Scale for Chronic Illness-8 Chronic Disease Stigma Scale-8(SSCI-8) scores, National Institute of Health Stroke Scale (NIHSS) scores and subtype of stroke were risk factors for PSD ( P<0.05). Binary Logistic regression analysis showed that diseased region at frontal lobe ( OR = 3.245, P = 0.011), basal ganglia region ( OR = 2.820, P = 0.007), cerebellar hemisphere ( OR = 4.594, P = 0.010) and serum cortisol ( OR = 1.174, P<0.001), hs-CRP ( OR = 1.057, P<0.001), SSCI-8 scores ( OR = 1.674, P<0.001), NIHSS scores ( OR = 1.283, P<0.001) were independent risk factors for PSD. Conclusions:PSD is a common complication in patients with stroke. Diseased region (at frontal lobe, basal ganglia region, cerebellar hemispheres), hs-CRP, serum cortisol, level of morbidity stigma and degree of neurological impairment are development risk factors for the PSD at 6 months of acute stroke.

Objective:To investigate the relationship of neutrophil/lymphocyte ratio (NLR) and early hematoma enlargement (HE) of intracerebral hemorrhage (ICH).Methods:Retrospectively analyzed the clinical data of 360 patients with ICH who were diagnosed and admitted to the Affiliated Hospital of Xuzhou Medical University from January 2017 to December 2017.Among them, 198 patients were selected for this study. According to the 24 h checked CT, they were divided into the hematoma expansion (HE) group (87 patients) and the non-HE group (111 patients). The clinical data of the two groups and the changes of hematology and imaging were compared.Results:Univariate analysis showed statistically significant differences of two groups in systolic blood pressure, diastolic blood pressure, Glasgow coma scale (GCS) score, hematoma volume at admission: (180.45 ± 25.90) mmHg(1 mmHg = 0.133 kpa) vs. (171.81 ± 25.87) mmHg, (103.29 ± 14.26) mmHg vs. (97.98 ± 14.81) mmHg, (11.05 ± 2.02) scores vs. (13.04 ± 1.58) scores, (25.14 ± 14.88) ml vs. (13.57 ± 11.98) ml; and GCS score, NLR , hematoma volume at 24 h after admission: (7.54 ± 2.04) scores vs. (11.04 ± 2.12) scores, 12.79 ± 7.24 vs. 5.59 ± 3.59, (17.07 ± 8.95) ml vs. (7.97 ± 3.56) ml, there were significant differences ( P<0.05). Logistic regression analysis showed that NLR, GCS, hematoma volumeat 24 h after admission and number of island sign were independent correlated factors of HE ( P<0.05). Receiver operation characteristic(ROC) curve analysis showed that when the NLR at 24 h after admission cut off value was 7.65, the sensitivity of predicting HE in patients with ICH was 78.16%, the specificity was 81.98%, and the area under the ROC curve was 0.852 (95% CI 0.798-0.907, P<0.001). Conclusions:HE have association with NLR, hematoma volume change.

Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To investigate the uncoupling protein 2 (UCP2) expression and its relations with apoptosis, oxidative stress and mitochondrial division/fusion in HT22 cell model with intracerebral hemorrhage.Methods:HT22 cells cultured in vitro were divided into control group, and groups of 3, 6, 12 and 24 h after modeling; cells in the later 4 groups were given 10 μmol/L hemin for 3, 6, 12 and 24 h, respectively, and cells in the control group were given the same equivalent solvent for 24 h. The apoptosis of HT22 cells in these 5 groups was detected by Annexin V-FITC/propidium iodide Apoptosis Detection Kit. The reactive oxygen species (ROS) expressions in these 5 groups were detected by fluorescence probe method. Western blotting was used to detect the protein expressions of UCP2, apoptosis-related protein cleaved caspase 3, anti-apoptosis protein B cell lymphoma/leukemia2 (bcl2), and mitochondrial division/fusion proteins (Fis1, Drp1, Opa1, and Mfn2). Results:As compared with the control group, groups of 3, 6, 12 and 24 h after modeling had significantly increased apoptosis rate, ROS level, and UCP2, cleaved caspase 3, Fis1 and Drp1 expressions, and statistically decreased bcl2, Opa1, and Mfn2 expressions. Groups of 3, 6, 12 and 24 h after modeling had successively increased apoptosis rate, successively increased ROS levels, and successively increased UCP2, cleaved caspase 3, Fis1 and Drp1 expressions, and successively decreased bcl2, Opa1, and Mfn2 expressions, with significant differences ( P<0.05). Conclusion:UCP2 expresses in HT22 cell model with intracerebral hemorrhage in time-dependent manner, and it has close relations with apoptosis, oxidative stress, and dynamic balance of mitochondrial division/fusion of HT22 cells.

OBJECTIVE: To explore the genetic basis for a patient with episodic ataxia and pyramidal tract signs. METHODS: The patient was subjected to high-throughput sequencing, Sanger sequencing and analysis of dynamic variant site associated with spinocerebellar ataxias (SCA). RESULTS: The patient was an adolescent male presenting with episodic ataxia, bilateral knee hyper-reflexia and ankle clonus. By genetic testing, he was found to harbor a c.1159-1162dupAAGT variant of PDHA1 gene. The same variant was not found in his parents and elder sister. No abnormalities were found by SCA dynamic variant screening. The patient was diagnosed as pyruvate dehydrogenase E1alpha deficiency due to variant of the PDHA1 gene. CONCLUSION The de novo c.1159-1162dupAAGT variant of the PDHA1 gene probably underlies the disease in the proband. Patients with pyruvate dehydrogenase E1alpha deficiency have complex phenotypes and very few have pyramidal tract involvement, which may be attributed to abnormal early neuronal development.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective To investigate the correlation between the progression of cerebral microbleed (CMB) and their distribution patterns in patients with lacunar infarction (LI) and the worsening of chronic kidney disease (CKD).Methods A prospective cohort study was used.Two hundred and fourteen patients with LI from June 2014 to June 2016 in Siyang People's Hospital of Jiangsu Province were consecutively selected.The clinical,laboratory and imaging-related data of patients were recorded in detail.The chronic kidney disease epidemiology collaboration (CKD-EPI) formula was used to estimate the estimation glomerular filtration rate (eGFR).After admission and 1-year'follow-up,head MRI (including gradient echo sequences) was performed,and the CMB distribution pattern was evaluated using the microbleed anatomical rating scale (MARS).Results Among the 214 patients with LI,90 patients were in CMB-positive group,of which simple lobe of brain CMB was in 16 cases,and deep/subtentorial CMB was in 74 cases,and 124 patients were in CMB-negative group.The baseline eGFR and eGFR classifications in CMB-negative group were significantly better than those in CMB-positive group,and there were statistical differences (P＜0.01 or ＜0.05).After 1 year'follow-up,worsening of CMB was in 45 cases,and worsening of CKD was in 22 cases.Multivariate Logistic regression analysis result showed that age and stroke history were independent risk factors for worsening of CMB in LI patients with simple lobe of brain CMB (OR =1.14 and 2.91,95％ CI 1.06 to 1.23 and 1.14 to 7.42,P＜0.01 or ＜0.05),and baseline eGFR and worsening of CKD were independent risk factors for worsening of CMB in LI patients with deep/subtentorial CMB (OR =0.90 and 4.11,95％ CI 0.87 to 0.94 and 1.04 to 16.21,P＜0.01 or ＜0.05).Conclusions Renal function in LI patients with CMB negative is significantly better than that in LI patients with CMB positive.In LI patients with deep/subtentorial CMB,the worsening of CMB is associated with worsening of CKD;in LI patients with simple lobe of brain CMB,the worsening of CMB is not associated with worsening of CKD.