1.Analysis of the Correlation between Plasma Fibrinogen and Osteoporosis Defined by Quantitative Computed Tomography
Yingna CHEN ; Kan SUN ; Na LI ; Chengzhi WANG ; Chulin HUANG ; Lingling LI ; Huisheng XIAO ; Guojuan LAO
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):147-153
[Objective]To clarify the associations between plasma fibrinogen(Fbg)and volumetric bone mineral density(vBMD)as well as osteoporosis measured by quantitative computed tomography(QCT),and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis.[Methods]Patients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis.The study analyzed the correlation between plasma Fbg and osteoporosis in patients.The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic(ROC)curve(AUC).[Results]Totally 441 subjects were included in the analysis,with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4%(28/441).As the level of plasma fibrinogen increased,the incidence of osteoporosis significantly increased(P<0.000 1)while the average bone mineral density of L1 and L2 were significantly decreased(P<0.05).Compared with the first quartile of plasma Fbg(1.99g/L-2.37g/L),the risk of osteoporosis in the fourth quartile of plasma Fbg(3.67g/L-4.46g/L)increased by 8.85 times after adjusting for related confounding factors.[Conclusion]This study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension.Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis,aiding in early diagnosis and therapeutic monitoring.This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.
2.One case of 18q-deletion syndrome with intellectual disability, epileptic seizures and white matter lesions and literature review
Yuhang DONG ; Yingjie DAI ; Huisheng CHEN
Chinese Journal of Neurology 2025;58(10):1064-1072
Objective:To report the clinical data of a patient with 18q-deletion syndrome primarily presenting with intellectual disability, seizures, and white matter lesions, and to summarize the phenotypic and genetic characteristics of this syndrome.Methods:The clinical data, auxiliary examinations, and genetic test results of a patient diagnosed with 18q-deletion syndrome in the Department of Neurology, General Hospital of Northern Theater Command in October 2023 were retrospectively collected. Additionally, literatures related to "18q-syndrome" "18q-deletion syndrome" were searched in the CNKI, Wanfang Database, and PubMed databases. Combining a review of relevant literature, the clinical phenotypes and genetic features of 18q-deletion syndrome were summarized.Results:The patient was a 17-year-old male presenting with seizures, severe intellectual disability (Mini-Mental State Examination score of 11), and white matter lesions on brain magnetic resonance imaging. Whole-exome sequencing and chromosomal microarray analysis confirmed an approximately 11.3 Mb copy number deletion in the 18q22.1-q23 region, involving dosage-sensitive genes such as TSHZ1, MBP, NETO1, and ZNF407, leading to a diagnosis of 18q- deletion syndrome. A literature review identified 18 previously reported cases of 18q-deletion syndrome, totaling 19 cases including this patient. The main clinical manifestations included facial dysmorphism (10/19), intellectual disability (9/19), mental and/or motor developmental delay (9/19), congenital heart disease (8/19), seizures (6/19) and white matter lesions (5/19). Pathogenic genes involved included TCF4, SMAD4, TSHZ1, ZNF407, ZNF516, and MBP. Conclusions:18q-deletion syndrome is caused by partial deletion of the long arm of chromosome 18, with neurological manifestations such as seizures, intellectual disability, and white matter lesions, exhibiting high phenotypic variability. Genetic testing aids in definitive diagnosis.
3.Safety and efficacy of thrombolysis in patients with acute mild ischemic stroke with tumor
Chinese Journal of Cerebrovascular Diseases 2025;22(1):3-14
Objective To investigate the safety and effectiveness of thrombolysis in patients with acute mild ischemic stroke with tumor.Methods All patients with acute mild(National Institute of Health stroke scale[NIHSS]score≤5 at admission)ischemic stroke who received intravenous thrombolysis with recombinant tissue plasminogen activator(rt-PA)or urokinase from April 1,2017 to July 1,2019 in the effectiveness of intravenous rt-PA versus urokinase for acute ischaemic stroke:a nationwide prospective Chinese registry study(INTRECIS)database were collected retrospectively,and they were divided into two groups according to whether they were accompanied by tumor or not:the combined tumor group and the non-tumor group.Collection of baseline and clinical data for all patients,including sex,age,cerebrovascular disease related risk factors(history of hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,stroke,smoking history,body mass index),baseline NIHSS score,baseline modified Rankin scale(mRS)score,baseline systolic blood pressure,baseline diastolic blood pressure,premedication use(antiplatelet agents,anticoagulants,lipid-lowering drugs),classification according to the trial of Org 10172 in acute stroke treatment,time from door to needle time,types of thrombolytic drugs(rt-PA and urokinase),and the type of tumor.Having a history of tumor is defined as having been diagnosed with a malignant tumor by a professionally certified oncologist prior to the administration of thrombolytic therapy,with no concurrent oncological treatment being received at the time of thrombolysis.Ninety days post-thrombolysis,patients were followed up through outpatient visits or telephone interviews,and their neurological status was assessed using the mRS.Score of mRS≤1 was considered as a good prognosis,while mRS score ≥ 2 indicated a poor prognosis,with a score of 6 representing death.Compare the baseline characteristics,primary safety endpoints,secondary safety endpoints,primary efficacy endpoints,and secondary efficacy endpoint events before and after 1∶1 propensity score matching(PSM)between the two groups with and without a history of tumor.The primary safety endpoint was symptomatic intracranial hemorrhage(defined as intracranial hemorrhage transformation,including parenchymal hematoma type 1,parenchymal hematoma type 2,hemorrhagic infarction type 1,hemorrhagic infarction type 2,observed on head CT within 36 h after thrombolysis,accompanied by worsening symptoms compared to at the time of thrombolysis and an increase in NIHSS score by ≥4 points from baseline)within 36 h after thrombolysis before and after 1∶1 PSM.The secondary safety endpoint is the incidence of various bleeding events within 36 h after thrombolysis,including asymptomatic intracranial hemorrhage(presence of intracranial hemorrhage without worsening of neurological deficit),systemic bleeding(other bleeding events besides intracranial hemorrhage),and mortality within 90 d after thrombolysis.The primary effectiveness endpoint was the proportion of patients with a good prognosis at 90 d after thrombolysis,and the secondary effectiveness endpoint was the proportion of patients with an NIHSS score≤1 at 1 d after thrombolysis.Before 1∶1 PSM,baseline characteristics that exhibited a P-value<0.1 when compared between the two groups were included in a multivariate Logistic regression analysis for adjustment.The differences in safety and efficacy endpoint events after intravenous thrombolysis between the two groups were compared before and after adjustment.After 1∶1 PSM,univariate binary Logistic regression analysis was conducted to assess whether there were significant differences in the safety and effectiveness of intravenous thrombolysis among acute mild ischemic stroke patients between those with and without tumor.Results A total of 1 680 patients with acute mild ischemic stroke,aged between 26 and 93 years,with a median age of 63(54,70)years,were included in this study,including 32 patients with tumor(including 3 cases of nasopharyngeal cancer,3 cases of rectal cancer,3 cases of reproductive system cancer,4 cases of breast cancer,5 cases of lung cancer,1 case of liver cancer,and 2 cases of gastric cancer and 11 cases of other tumors)and 1 648 patients without tumor.There were 32 cases in both groups after 1∶1 PSM.(1)Before 1∶1 PSM,patients with tumor group were older than those in the non-tumor group(67[61,74]years vs.62[54,70]years,P=0.01).After 1∶1 PSM,there were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).(2)Primary safety endpoints:before 1∶1 PSM,there was no patient had symptomatic intracranial hemorrhage,asymptomatic intracranial hemorrhage,systemic bleeding in the group with tumor,while 0.4%(6/1 648),1.0%(17/1 648),0.2%(3/1 648)occurred respectively in the group without tumor.There were no statistically significant differences in both primary and secondary safety endpoints between the two groups(both P=0.99).After 1∶1 PSM,neither group experienced symptomatic intracranial hemorrhage,asymptomatic intracranial hemorrhage,or systemic hemorrhage.No deaths occurred in the tumor group within 90 d after thrombolysis,while one death occurred in the non-tumor group.(3)Primary efficacy endpoints:before 1∶1 PSM,there was no statistically significant difference in the proportion of patients with good prognosis at 90 d after intravenous thrombolysis between the two groups(90.6%[29/32]vs.86.9%[1 432/1 648],P=0.54).After adjusting for confounding factors such as age and coronary heart disease,there was no statistically significant difference(OR,1.58,95%CI0.48-5.26,P=0.45)in the proportion of patients with a good prognosis at 90 d after intravenous thrombolysis between the two groups.After 1∶1 PSM,90.6%(29/32)patients in the tumor group had a good prognosis at 90d after intravenous thrombolysis,while 84.4%(27/32)patients in the non-tumor group,there was no statistically significant difference between the two groups(OR,0.56,95%CI 0.12-2.57,P=0.71).Secondary efficacy endpoint:before 1∶1 PSM,there was no statistically significant difference in the proportion of patients with an NIHSS score≤1 at 1 d after intravenous thrombolysis(37.5%[12/32]vs.48.2%[795/1 648],P=0.23),after adjusting for confounding factors such as age and coronary heart disease,the results suggest that there was no statistically significant difference in the proportion of patients with an NIHSS score≤1 at 1 d after intravenous thrombolysis(OR,0.65,95%CI 0.32-1.34,P=0.24).After 1∶1 PSM,the proportion of patients with an NIHSS score≤1 at 1 d after thrombolysis was 37.5%(12/32)in both patient groups,there was no statistically significant difference between the two groups(OR,1.00,95%CI 0.36-2.75,P=0.99).Conclusions Compared with patients without tumor,acute mild ischemic stroke in China with tumor may exhibit similar safety and effectiveness in receiving intravenous thrombolysis with rt-PA or urokinase.The findings of this study await further validation through randomized controlled trials.
4.Safety and efficacy of thrombolysis in patients with acute mild ischemic stroke with tumor
Chinese Journal of Cerebrovascular Diseases 2025;22(1):3-14
Objective To investigate the safety and effectiveness of thrombolysis in patients with acute mild ischemic stroke with tumor.Methods All patients with acute mild(National Institute of Health stroke scale[NIHSS]score≤5 at admission)ischemic stroke who received intravenous thrombolysis with recombinant tissue plasminogen activator(rt-PA)or urokinase from April 1,2017 to July 1,2019 in the effectiveness of intravenous rt-PA versus urokinase for acute ischaemic stroke:a nationwide prospective Chinese registry study(INTRECIS)database were collected retrospectively,and they were divided into two groups according to whether they were accompanied by tumor or not:the combined tumor group and the non-tumor group.Collection of baseline and clinical data for all patients,including sex,age,cerebrovascular disease related risk factors(history of hypertension,diabetes mellitus,coronary artery disease,atrial fibrillation,stroke,smoking history,body mass index),baseline NIHSS score,baseline modified Rankin scale(mRS)score,baseline systolic blood pressure,baseline diastolic blood pressure,premedication use(antiplatelet agents,anticoagulants,lipid-lowering drugs),classification according to the trial of Org 10172 in acute stroke treatment,time from door to needle time,types of thrombolytic drugs(rt-PA and urokinase),and the type of tumor.Having a history of tumor is defined as having been diagnosed with a malignant tumor by a professionally certified oncologist prior to the administration of thrombolytic therapy,with no concurrent oncological treatment being received at the time of thrombolysis.Ninety days post-thrombolysis,patients were followed up through outpatient visits or telephone interviews,and their neurological status was assessed using the mRS.Score of mRS≤1 was considered as a good prognosis,while mRS score ≥ 2 indicated a poor prognosis,with a score of 6 representing death.Compare the baseline characteristics,primary safety endpoints,secondary safety endpoints,primary efficacy endpoints,and secondary efficacy endpoint events before and after 1∶1 propensity score matching(PSM)between the two groups with and without a history of tumor.The primary safety endpoint was symptomatic intracranial hemorrhage(defined as intracranial hemorrhage transformation,including parenchymal hematoma type 1,parenchymal hematoma type 2,hemorrhagic infarction type 1,hemorrhagic infarction type 2,observed on head CT within 36 h after thrombolysis,accompanied by worsening symptoms compared to at the time of thrombolysis and an increase in NIHSS score by ≥4 points from baseline)within 36 h after thrombolysis before and after 1∶1 PSM.The secondary safety endpoint is the incidence of various bleeding events within 36 h after thrombolysis,including asymptomatic intracranial hemorrhage(presence of intracranial hemorrhage without worsening of neurological deficit),systemic bleeding(other bleeding events besides intracranial hemorrhage),and mortality within 90 d after thrombolysis.The primary effectiveness endpoint was the proportion of patients with a good prognosis at 90 d after thrombolysis,and the secondary effectiveness endpoint was the proportion of patients with an NIHSS score≤1 at 1 d after thrombolysis.Before 1∶1 PSM,baseline characteristics that exhibited a P-value<0.1 when compared between the two groups were included in a multivariate Logistic regression analysis for adjustment.The differences in safety and efficacy endpoint events after intravenous thrombolysis between the two groups were compared before and after adjustment.After 1∶1 PSM,univariate binary Logistic regression analysis was conducted to assess whether there were significant differences in the safety and effectiveness of intravenous thrombolysis among acute mild ischemic stroke patients between those with and without tumor.Results A total of 1 680 patients with acute mild ischemic stroke,aged between 26 and 93 years,with a median age of 63(54,70)years,were included in this study,including 32 patients with tumor(including 3 cases of nasopharyngeal cancer,3 cases of rectal cancer,3 cases of reproductive system cancer,4 cases of breast cancer,5 cases of lung cancer,1 case of liver cancer,and 2 cases of gastric cancer and 11 cases of other tumors)and 1 648 patients without tumor.There were 32 cases in both groups after 1∶1 PSM.(1)Before 1∶1 PSM,patients with tumor group were older than those in the non-tumor group(67[61,74]years vs.62[54,70]years,P=0.01).After 1∶1 PSM,there were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).(2)Primary safety endpoints:before 1∶1 PSM,there was no patient had symptomatic intracranial hemorrhage,asymptomatic intracranial hemorrhage,systemic bleeding in the group with tumor,while 0.4%(6/1 648),1.0%(17/1 648),0.2%(3/1 648)occurred respectively in the group without tumor.There were no statistically significant differences in both primary and secondary safety endpoints between the two groups(both P=0.99).After 1∶1 PSM,neither group experienced symptomatic intracranial hemorrhage,asymptomatic intracranial hemorrhage,or systemic hemorrhage.No deaths occurred in the tumor group within 90 d after thrombolysis,while one death occurred in the non-tumor group.(3)Primary efficacy endpoints:before 1∶1 PSM,there was no statistically significant difference in the proportion of patients with good prognosis at 90 d after intravenous thrombolysis between the two groups(90.6%[29/32]vs.86.9%[1 432/1 648],P=0.54).After adjusting for confounding factors such as age and coronary heart disease,there was no statistically significant difference(OR,1.58,95%CI0.48-5.26,P=0.45)in the proportion of patients with a good prognosis at 90 d after intravenous thrombolysis between the two groups.After 1∶1 PSM,90.6%(29/32)patients in the tumor group had a good prognosis at 90d after intravenous thrombolysis,while 84.4%(27/32)patients in the non-tumor group,there was no statistically significant difference between the two groups(OR,0.56,95%CI 0.12-2.57,P=0.71).Secondary efficacy endpoint:before 1∶1 PSM,there was no statistically significant difference in the proportion of patients with an NIHSS score≤1 at 1 d after intravenous thrombolysis(37.5%[12/32]vs.48.2%[795/1 648],P=0.23),after adjusting for confounding factors such as age and coronary heart disease,the results suggest that there was no statistically significant difference in the proportion of patients with an NIHSS score≤1 at 1 d after intravenous thrombolysis(OR,0.65,95%CI 0.32-1.34,P=0.24).After 1∶1 PSM,the proportion of patients with an NIHSS score≤1 at 1 d after thrombolysis was 37.5%(12/32)in both patient groups,there was no statistically significant difference between the two groups(OR,1.00,95%CI 0.36-2.75,P=0.99).Conclusions Compared with patients without tumor,acute mild ischemic stroke in China with tumor may exhibit similar safety and effectiveness in receiving intravenous thrombolysis with rt-PA or urokinase.The findings of this study await further validation through randomized controlled trials.
5.One case of 18q-deletion syndrome with intellectual disability, epileptic seizures and white matter lesions and literature review
Yuhang DONG ; Yingjie DAI ; Huisheng CHEN
Chinese Journal of Neurology 2025;58(10):1064-1072
Objective:To report the clinical data of a patient with 18q-deletion syndrome primarily presenting with intellectual disability, seizures, and white matter lesions, and to summarize the phenotypic and genetic characteristics of this syndrome.Methods:The clinical data, auxiliary examinations, and genetic test results of a patient diagnosed with 18q-deletion syndrome in the Department of Neurology, General Hospital of Northern Theater Command in October 2023 were retrospectively collected. Additionally, literatures related to "18q-syndrome" "18q-deletion syndrome" were searched in the CNKI, Wanfang Database, and PubMed databases. Combining a review of relevant literature, the clinical phenotypes and genetic features of 18q-deletion syndrome were summarized.Results:The patient was a 17-year-old male presenting with seizures, severe intellectual disability (Mini-Mental State Examination score of 11), and white matter lesions on brain magnetic resonance imaging. Whole-exome sequencing and chromosomal microarray analysis confirmed an approximately 11.3 Mb copy number deletion in the 18q22.1-q23 region, involving dosage-sensitive genes such as TSHZ1, MBP, NETO1, and ZNF407, leading to a diagnosis of 18q- deletion syndrome. A literature review identified 18 previously reported cases of 18q-deletion syndrome, totaling 19 cases including this patient. The main clinical manifestations included facial dysmorphism (10/19), intellectual disability (9/19), mental and/or motor developmental delay (9/19), congenital heart disease (8/19), seizures (6/19) and white matter lesions (5/19). Pathogenic genes involved included TCF4, SMAD4, TSHZ1, ZNF407, ZNF516, and MBP. Conclusions:18q-deletion syndrome is caused by partial deletion of the long arm of chromosome 18, with neurological manifestations such as seizures, intellectual disability, and white matter lesions, exhibiting high phenotypic variability. Genetic testing aids in definitive diagnosis.
6.Correlation between serum remnant lipoprotein cholesterol,triglyceride levels and coronary heart disease in middle-aged people
Qihua LI ; Liu MIAO ; Huisheng CHEN ; Jianhong CHEN
Chinese Journal of Arteriosclerosis 2024;32(11):963-971
Aim To investigate the correlation between serum remnant lipoprotein cholesterol(RLP-C),triglyc-eride levels(TG)and coronary heart disease(CHD)in middle-aged people.Methods A total of 439 middle-aged in-dividuals who were hospitalized in the Department of Cardiology of Liuzhou People's Hospital from January 2015 to Decem-ber 2022 and underwent coronary angiography were selected as the research subjects.They were divided into CHD group(190 cases)and control group(249 cases)according to the results of coronary angiography.The general clinical data and laboratory tests of the subjects were collected,and RLP-C was calculated based on blood lipid profile.Bivariate Spearman correlation,multivariate Logistic regression,and restricted cubic spline graph were used to analyze the correlation between RLP-C,TG,and CHD in these middle-aged participants.Receiver operating characteristic(ROC)curve was used to evaluate the value of RLP-C and TG in predicting CHD.Results The age in CHD group was older than that in control group,proportion of male,proportion of smoking history,incidence of hypertension,incidence of diabetes,inci-dence of hyperlipidemia,body mass index(BMI),systolic blood pressure(SBP),fasting blood glucose(FBG),glycosy-lated hemoglobin(HbA1c),TG,low density lipoprotein cholesterol(LDLC),RLP-C were higher than those in control group,while high density lipoprotein cholesterol(HDLC)was lower than that in control group(P<0.05).The Spearman correlation analysis results showed positive correlation between RLP-C,TG,LDLC and CHD(r=0.227,0.279,and 0.105,respectively,P<0.05),and negative correlation between HDLC and CHD(r=-0.340,P<0.001)in these stud-ied population.Multivariate Logistic regression analysis showed that whether as continuous or categorical variables,RLP-C and TG were independent risk factors for CHD(P<0.05),HDLC was independent protective factor for CHD(P<0.05).Compared with lowest quartile group,The OR(95%CI)of CHD incidence in 3rd and 4th quartile group of RLP-C were 2.648(1.364~5.144)and 2.847(1.468-5.520)respectively;The OR(95%CI)of CHD incidence in 3rd and 4th quartile group of TG were 3.043(1.520-6.092)and 3.520(1.811~6.842)respectively.The restricted cubic spline graph revealed that RLP-C,TG were positively nonlinearly correlated with CHD(P for overall<0.001,P for nonlin-ear=0.002,0.001,respectively).Subgroup analysis showed that the relationship between RLP-C,TG and CHD was more significant in females than in males.ROC curve analysis showed that the areas under the curve(95%CI)of RLP-C,TG in predicting CHD were 0.632(0.580-0.685)(P<0.001)and 0.663(0.612-0.713)(P<0.001)in general,meanwhile,0.735(0.659-0.811)(P<0.001)and 0.740(0.666-0.813)(P<0.001)in females.Conclusion RLP-C and TG are independent risk factors for CHD in middle-aged people,and their correlation with CHD are greater than that of LDLC.They may become the main targets for the prevention and treatment of CHD,and should be given clinical attention.
7.Effectiveness and safety of intravenous urokinase for acute ischemic stroke: a dose explorative study based on a prospective cohort
Chuwei ZHANG ; Xinhong WANG ; Huisheng CHEN
Chinese Journal of Neurology 2024;57(12):1342-1352
Objective:To analyze the optimal dose of urokinase (UK) for intravenous thrombolysis in Chinese patients with acute ischemic stroke within 4.5 hours of onset.Methods:Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 hours of onset (INTRECIS) cohort, consecutive patients who received intravenous UK from April 1, 2017 to July 1,2019 were retrospectively collected . According to the tertile dose of UK per body weight, eligible patients were divided into low dose group [(1.00-1.67)×10 4 international unit per kilogram], moderate dose group [(1.68-2.33)×10 4 international unit per kilogram] and high dose group (2.34-3.00)×10 4 international unit per kilogram]. Furthermore, subgroups were analyzed according to age, gender, and baseline National Institutes of Health Stroke Scale (NIHSS) scores. The primary efficacy outcome was excellent functional outcome, defined as a 90-day modified Rankin Scale (mRS) score of 0-1. The secondary efficacy outcomes included favorable functional outcome (mRS score of 0-2 at 90 days), mRS score distribution at 90 days and changes in NIHSS score at 1 day and 14 days, compared with the baseline. The primary safety outcome was symptomatic intracranial hemorrhage (sICH), and the secondary safety outcomes included recurrence of stroke within 90 days, all-cause mortality and any random bleeding events. Results:A total of 1 144 patients were included in the analysis: 549 in the low dose group, 509 in the moderate dose group and 86 in the high dose group. The proportion of excellent functional outcome was higher in the high dose group, compared with the low dose group [79.07% (68/86) vs 67.03% (368/549), OR=2.427, 95% CI 1.280-4.587, P=0.007] and the moderate dose group [79.07%(68/86) vs 70.53%(359/509), OR=1.942, 95% CI 1.023-3.690, P=0.043]. The incidence of sICH was similar among the 3 groups [high dose group vs low dose group: 1.16% (1/86) vs 2.00% (11/549), OR=0.607, 95% CI 0.071-5.153, P=0.648; high dose group vs moderate dose group: 1.16%(1/86) vs 0.79% (4/509), OR=0.330, 95% CI 0.101-1.074, P=0.596]. The subgroup analysis showed that higher proportion of excellent functional outcome was found in the high dose group patients with senior citizens (≥60 years old) [high dose group vs low dose group: 80.70% (46/57) vs 63.07% (222/352), OR=3.401, 95% CI 1.500-7.752, P=0.003; high dose group vs moderate dose group: 80.70% (46/57) vs 69.63% (227/326), OR=2.381, 95% CI 1.074-5.291, P=0.033], moderate neurologic deficit (NIHSS score 4-16) [high dose group vs low dose group:79.07% (34/43) vs 62.61% (211/337), OR=2.604, 95% CI 1.190-5.682, P=0.017; high dose group vs moderate dose group:79.07% (34/43) vs 65.02% (184/283), OR=2.315, 95% CI 1.055-5.097, P=0.036], and large artery atherosclerosis [high dose group vs low dose group: 81.40% (35/43) vs 62.32% (177/284), OR=3.584, 95% CI 1.416-9.009, P=0.007; high dose group vs moderate dose group: 81.40% (35/43) vs 66.06% (144/218), OR=2.793, 95% CI 1.090-7.143, P=0.032]. Conclusions:Intravenous UK dose calculated according to body weight may be reasonable for treating acute ischemic stroke. Intravenous UK with dose of (2.34-3.00)×10 4 international unit per kilogram may favor better benefit for acute ischemic stroke, which warrants further confirmation.
8.Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension
Huisheng CHEN ; Yi YANG ; Jun NI ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Shugen HAN ; Runxiu ZHU ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Xiaofei YU ; Liying CUI
Chinese Journal of Internal Medicine 2022;61(8):916-920
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.
9.Hyperintense plaque coexisting with positive remodeling in stenotic middle cerebral artery may be associated with cerebral infarction mechanism
Jijie WANG ; Yue WANG ; Ziyang SHANG ; Lin TAO ; Huisheng CHEN
Chinese Journal of Neurology 2022;55(10):1128-1134
Objective:To investigate the association between plaque vulnerability characteristics and infarction sub-types in patients with acute unilateral anterior circulation cerebral infarction due to intracranial atherosclerotic disease.Methods:A total of 58 eligible patients who underwent intracranial high-resolution magnetic resonance imaging (HRMRI) were finally enrolled in the retrospective study from December 2018 to December 2020. In the current study, all patients were classified into the group with artery-to-artery (A-to-A) embolic infarction ( n=32) and the group without ( n=26), according to infarction sub-types on diffusion-weighted imaging. Baseline information, the presence/absence of hyperintense plaque, irregular plaque surface, remodeling pattern and quadrant distribution by HRMRI were collected and evaluated. Multivariate Logistic regression analysis was performed to determine the relationship between plaque vulnerability and infarction sub-types. Furthermore, the analysis of interaction between hyperintense plaque and positive remodeling in response to A-to-A embolism was visualized by Sankey diagram. Results:The presence of hyperintense plaque ( OR=3.90, 95% CI 1.21-12.59, P=0.023) and arterial remodeling patterns (positive remodeling vs intermediate state, OR=4.32, 95% CI 0.86-21.49, P for trend=0.027) were the strong independent predictors for A-to-A embolism. Importantly, a significantly positive synergy between the remodeling pattern and hyperintense plaque in response to infarction sub-types was found by Sankey diagram ( Wald=10.044, P for interaction=0.007). Similarly, in receiver operating characteristic curve analysis, the discrimination of hyperintense plaque combined with positive remodeling for A-to-A embolism was significantly superior to that of either biomarker alone (area under the curve=0.710, 95% CI 0.576-0.845, P=0.006). Conclusion:A synergistic effect between positive remodeling and hyperintense plaque can promote plaque vulnerability, suggesting a potential target sub-population may benefit from stroke prevention with intensive antithrombotic therapy, although this must be confirmed in future.
10.Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit
Jun NI ; Huisheng CHEN ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Yi YANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Liying CUI
Chinese Journal of Neurology 2022;55(5):474-480
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.

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