BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective To investigate the relationship between serum anticardiolipin antibody-immune globulin G (ACA-IgG),interleukin-10 (IL-10 ),IL-17 levels and intracranial large-artery atherosclerotic stenosis in patients with ischemic stroke. Methods From March 2014 to March 2015,a total of 176 consecutive patients with the first-ever ischemic stroke admitted to the Department of Neurology,Liaocheng People′s Hospital,Shandong Province,China,and performed DSA were enrolled prospectively. Seven of the patients with cardiogenic embolism,5 with moyamoya disease,8 with arteritis,2 with artery dissection,9 with autoimmune diseases or acute and chronic inflammation were excluded,21 with extracranial arterial stenosis were not enrolled,and finally 124 were enrolled in the study. According to the findings of DSA,the degrees of intracranial large artery stenosis were divided into a stenosis-free group (n = 34),a mild-stenosis group (n = 30),a moderate-stenosis group (n = 32),and a severe-stenosis group (n = 28). The differences of serum ACA-IgG,IL-10,IL-17 levels and baseline factors of the 4 groups were compared,and multivariate logistic regression analysis was used to analyze several factors that affected intracranial large-artery stenosis. Results There were no significant differences in sex,age,alcohol consumption rate,smoking rate,and incidence of hyperlipidemia among the 4 groups of patients (all P >0. 05). Compared with the stenosis-free group,there were significant differences in the incidences of hypertension and diabetes among the mild-stenosis,moderate-stenosis and severe-stenosis groups (the incidence of hypertension,80. 0% [n = 24],93. 8% [n = 30],89. 3% [n = 25]vs. 55. 9% [19 cases];χ2 = 8. 271,8. 920,and 10. 877,respectively;P = 0. 038,0. 032,and 0. 014,respectively). The incidences of diabetes were 33. 3% (n = 10),43. 8% (n = 14),60. 7% (n = 17)vs. 8. 8% (n = 3),(χ2 = 7. 960, 8. 733,and 9. 285,respectively;P = 0. 043,0. 035,and 0. 027,respectively). Incidence of diabetes of the severe-stenosis group was higher than that of the mild-stenosis group (χ2 = 9. 348,P = 0. 025). There were no significant differences in the incidences of hypertension and diabetes among other groups (all P >0. 05). There were significant differences in ACA-IgG levels (23 ± 5,39 ± 8,51 ± 9,and 65 ± 10 kU/ L);IL-10 levels (108 ± 33,85 ± 25,77 ± 21,and 62 ± 19 ng/ L),and IL-17 levels (38 ± 10,58 ± 22,63 ± 31, and 75 ± 26 ng/ L)among the stenosis-free,mild,moderate and severe-stenosis groups (F = 17. 754,9. 827, and 12. 656;respectively;all P < 0. 01). Compared with the stenosis-free group,the ACA-IgG and IL-17 levels of the patients in the mild,morderate,and severe stenosis groups increased significantly (ACA-IgG level:t =2. 307,2. 559,and 3. 374,respectively;P = 0. 026,0. 014,and 0. 001,respectively,the IL-17 levels:t =2. 183,2. 549 and 3. 159,respectively;P = 0. 037,0. 013,and 0. 002,respectively),while the IL-10 level decreased significantly. There were significant differences among the groups (t = 2. 036,2. 351,and 2. 762, respectively;P = 0. 042,0. 023,and 0. 006,respectively). Compared with the mild-stenosis group,the ACA-IgG and IL-17 levels of the severe stenosis group increased significantly (t = 3. 154 and 2. 976 respectively;P = 0. 002 and 0. 004 respectively). There were no significant differences among the pairwise comparisons of other groups (P >0. 05). The results of logistic regression analysis showed that hypertension, diabetes,ACA-IgG level,and IL-17 level were the risk factors for intracranial large-artery stenosis (OR, 3. 043,95% CI 1. 606 -5. 875,P = 0. 003;OR,2. 912,95% CI 1. 513 -5. 824,P < 0. 01;OR,1. 837,95% CI 2. 057-3. 416,P = 0. 037;OR,1. 453,95% CI 1. 346 -2. 721,P = 0. 014). Conclusion ACA-IgG and IL-17 may play an important role in the occurrence and development processes of intracranial large-artery atherosclerotic stenosis.

Objective To observe the effect of dual-task interference on postural sway and hand flexibility of patients with early Parkinson's disease (PD).Methods Twenty-tree patients with early PD and twcnty-three healthy,sex-and age-matched control subjects were examined.Postural sway was measured with an accelerometer at the centre of mass at the lower spine.Two parameters of postural sway were computed from the acceleration signals including root mean square acceleration (RMS) and jerkiness of sway (JERK).Purdue pegboard test,single-task tests and dual-task test were performed respectively to record the numbers of nails inserted with left hand,right hand and both hands within 30 seconds.Results In the usual conditions,no significant differences of postural sway parameters were found between the control group and PD group in eye open and eye closed condition.In dualtask condition,PD patients showed an increase of RMS values (eye open conditions:PD group (0.156±0.112) m/s2,control group (0.086±0.026) m/s2;eye closed conditions:PD group (0.204±0.162)m/s2,control group (0.095±0.023)m/s2) of sway acceleration,compared with control subjects (P＜0.01).These differences reached significance during cognitive task performance in eye open and eye closed with dual task.PD patients showed larger JERK values with increasing difficulty of the sway task which also reached significance during cognitive task performance(P＜0.05).The number of pegs inserted within 30 s in patients with PD (17.33±4.87)was significantly lower than that in controls (20.77±4.13) (P＜0.05).Conclusion The hand flexibility of patients with early PD obviously decrease.The balance of patients with early PD may deteriorate when their attention is diverted or reduced because of attempting to perform cognitive tasks.

Objective To explore the relationship between the serum anticardiolipin antibody (ACA),vascular endothelial grow factor (VEGF) concentration and cognitive impairment in patients with ischemic stroke.Methods Totally 128 cases with acute ischemic stroke were admmitted in stroke unit ward of our hospital during June 2014 to December 2014.According to the score of Montreal cognitive assessnent (MoCA),128 patients with ischemic stroke were divided into groups A (53 cases with cognitive impairment) and group B (75 cases without cognitive impairment).The concentrations of serum ACA,VEGF were quantitatively determinated by ELISA.The differences of serum ACA,VEGF concentrations were compared between the two groups.Results Compared with normal cognitive function group,the cognitive impairment patients had significantly higher ACA concentration ((0.86±0.16) mg/L vs (0.52±0.08) mg/L,P＜0.01),and lower VEGF concentration ((197.60±7.48) pg/ml vs (205.80±8.52) pg/ml,P＜0.05).Logistic regression revealed that ACA and VEGF were independent effect factors for cognitive impairment (ACA:B =2.841,OR =0.33,95 ％ CI =0.118-0.926,P=0.025.V EGF:B =-1.674,OR =4.99,95％ CI =1.688-4.741,P=0.034).Conclusion ACA and VEGF may play an important role in cognitive impairment after ischemic stroke.