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Zhi Chen, Jingyu Chen, Hongpin Miao, Fei Li, Hua Feng, and Gang Zhu

Hemorrhagic events associated with cerebral paragonimiasis are not rare, especially in children and adolescents; however, angiographic evidence of cerebrovascular involvement has not been reported. The authors describe angiographic abnormalities of the cerebral arteries seen in 2 children in whom cerebral paragonimiasis was associated with hemorrhagic stroke. The patients presented with acute intracerebral and subarachnoid hemorrhage. Angiography revealed a beaded appearance and long segmental narrowing of arteries, consistent with arteritis. In both patients, involved vessels were seen in the area of the hemorrhage. The vascular changes and the hemorrhage, together with new lesions that developed close to the hemorrhage and improved after praziquantel treatment, were attributed to paragonimiasis. Further study of the frequency and mechanism of hemorrhagic cerebrovascular complications associated with cerebral paragonimiasis is needed.

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Xian-xin Qiu, Chen-hong Wang, Zhi-xiong Lin, Na You, Xing-fu Wang, Yu-peng Chen, Long Chen, Shui-yuan Liu, and De-zhi Kang

OBJECT

Peritumoral brain edema (PTBE) is a common phenomenon associated with high-grade gliomas (HGGs). In this study, the authors investigated the expression of Notch delta-like ligand 4 (DLL4) and its correlation with PTBE and prognosis in patients with an HGG.

METHODS

Tumors from 99 patients with HGG were analyzed for DLL4 expression using immunohistochemistry. PTBE on preoperative MR images and the relationship between PTBE and DLL4 expression were evaluated. The effect of DLL4 on patient prognosis was assessed by using Kaplan-Meier survival and Cox proportional hazard models.

RESULTS

Immunohistochemistry results revealed that the expression of DLL4 was distributed primarily within the cytoplasm of tumor vascular endothelial cells and seldom detected in tumor cells. DLL4 expression was correlated positively with the degree of edema (r = 0.845 and p < 0.001, Spearman’s test). In addition, DLL4 was an independent predictor of prognosis in patients with HGGs (p = 0.001).

CONCLUSIONS

DLL4 expression was correlated positively with the degree of PTBE and was an independent unfavorable prognostic indicator in patients with HGG.

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Zhiyuan Yu, Jun Zheng, Rui Guo, Chao You, Hao Li, and Lu Ma

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Chen-Yu Ding, Han-Pei Cai, Hong-Liang Ge, Liang-Hong Yu, Yuan-Xiang Lin, and De-Zhi Kang

OBJECTIVE

The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.

METHODS

The authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.

RESULTS

Forty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).

CONCLUSIONS

The serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

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Jingyu Chen, Zhi Chen, Fei Li, Jiangkai Lin, Hui Meng, and Hua Feng

Object

The purpose of this study was to review 14 rare cases of cerebral paragonimiasis that first manifested as intracranial hemorrhage (ICH), and to investigate the characteristics of clinical manifestation, diagnosis, and treatment of the disease.

Methods

The authors have encountered 14 cases of cerebral paragonimiasis in patients between the ages of 6 and 16 years (mean age 11.5 years) who presented with sudden headache, nausea, and vomiting. Three of them were affected with varying degrees of limb hemiplegia, and in 1 this was combined with high fever; the blood eosinophil count and enzyme-linked immunosorbent assay showed positive results too. The ICHs were observed with cranial CT and MR imaging, and lung lesions were also detected in 5 cases on chest CT scans. Ten of the diagnosed cases were treated with oral praziquantel. Three of these patients were given carbamazepine from the beginning of parasiticidal treatment to prevent seizures; 4 of the remaining 7 patients experienced epileptic seizures during the treatment process. Four patients needed surgery to remove the lesions, and these individuals received praziquantel treatment right after the surgery.

Results

Pathological examinations demonstrated eosinophilic granuloma in these patients. There was no disease recurrence or epilepsy in 11–40 months of follow-up; however, mild hemiplegia could still be observed in 2 cases after 12 months and 17 months of follow-up.

Conclusions

The possibility of cerebral paragonimiasis should be considered when ICH is detected in young patients who are either from an endemic area or have recently visited such an area; the relatively small amount of hemorrhage in cerebral paragonimiasis is often represented as small lesions surrounded by disproportionately larger edema on the imaging study. Preventive antiepileptic drugs should be used along with the administration of parasiticide.

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Xin-Zhi Sun, Zhong-Qiang Chen, Qiang Qi, Zhao-Qing Guo, Chui-Guo Sun, Wei-Shi Li, and Yan Zeng

Object

In this paper, the authors aimed to summarize the clinical characteristics of ossification of the ligamentum flavum (OLF) associated with dural ossification (DO) and to identify improved methods for preoperative diagnosis.

Methods

Thirty-six patients who had undergone OLF surgery between February 2005 and September 2009 were included in this retrospective study. The patients were divided into 2 groups: one that included patients with intraoperative evidence of DO and a second group that included patients without DO. The clinical features of DO were summarized and the neurological status of the patients was evaluated pre- and postoperatively.

Results

The incidence rate of DO associated with OLF was 39% (14/36). The sensitivity and specificity of the tram track sign were found to be 93% and 59%, respectively. Dural ossification was found among 86% of the patients with tuberous type Sato classification. The postoperative neurological status of patients was generally improved relative to that observed prior to surgery, although neurological recovery did not differ between the 2 groups. Cerebrospinal fluid leakage was the main complication, occurring predominantly in the patients with DO, and all leaks resolved in all patients after comprehensive treatments.

Conclusions

The tram track sign and Sato classification were found to be useful for preoperative diagnosis of DO and for determining the surgical procedure to be performed. Dural ossification had no effect on postoperative neurological recovery.

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Qiang Tan, Qianwei Chen, Yin Niu, Zhou Feng, Lin Li, Yihao Tao, Jun Tang, Liming Yang, Jing Guo, Hua Feng, Gang Zhu, and Zhi Chen

OBJECTIVE

Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study.

METHODS

Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor–κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH.

RESULTS

In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH.

CONCLUSIONS

This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

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Xin Zhang, Tamrakar Karuna, Zhi-Qiang Yao, Chuan-Zhi Duan, Xue-Min Wang, Shun-Ting Jiang, Xi-Feng Li, Jia-He Yin, Xu-Ying He, Shen-Quan Guo, Yun-Chang Chen, Wen-Chao Liu, Ran Li, and Hai-Yan Fan

OBJECTIVE

Among clinical and morphological criteria, hemodynamics is the main predictor of aneurysm growth and rupture. This study aimed to identify which hemodynamic parameter in the parent artery could independently predict the rupture of anterior communicating artery (ACoA) aneurysms by using multivariate logistic regression and two-piecewise linear regression models. An additional objective was to look for a more simplified and convenient alternative to the widely used computational fluid dynamics (CFD) techniques to detect wall shear stress (WSS) as a screening tool for predicting the risk of aneurysm rupture during the follow-up of patients who did not undergo embolization or surgery.

METHODS

One hundred sixty-two patients harboring ACoA aneurysms (130 ruptured and 32 unruptured) confirmed by 3D digital subtraction angiography at three centers were selected for this study. Morphological and hemodynamic parameters were evaluated for significance with respect to aneurysm rupture. Local hemodynamic parameters were obtained by MR angiography and transcranial color-coded duplex sonography to calculate WSS magnitude. Multivariate logistic regression and a two-piecewise linear regression analysis were performed to identify which hemodynamic parameter independently characterizes the rupture status of ACoA aneurysms.

RESULTS

Univariate analysis showed that WSS (p < 0.001), circumferential wall tension (p = 0.005), age (p < 0.001), the angle between the A1 and A2 segments of the anterior cerebral artery (p < 0.001), size ratio (p = 0.023), aneurysm angle (p < 0.001), irregular shape (p = 0.005), and hypertension (grade II) (p = 0.006) were significant parameters. Multivariate analyses showed significant association between WSS in the parent artery and ACoA aneurysm rupture (p = 0.0001). WSS magnitude, evaluated by a two-piecewise linear regression model, was significantly correlated with the rupture of the ACoA aneurysm when the magnitude was higher than 12.3 dyne/cm2 (HR 7.2, 95% CI 1.5–33.6, p = 0.013).

CONCLUSIONS

WSS in the parent artery may be one of the reliable hemodynamic parameters characterizing the rupture status of ACoA aneurysms when the WSS magnitude is higher than 12.3 dyne/cm2. Analysis showed that with each additional unit of WSS (even with a 1-unit increase of WSS), there was a 6.2-fold increase in the risk of rupture for ACoA aneurysms.

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Yi-Syuan Li, Chun-Yu Chen, Chi-Hui Chen, Zhi-Kang Yao, Yu-Hsiang Sung, Kai-Cheng Lin, Yih-Wen Tarng, Chien-Jen Hsu, and Jenn-Huei Renn

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Abudumijiti Aibaidula, Wang Zhao, Jin-song Wu, Hong Chen, Zhi-feng Shi, Lu-lu Zheng, Ying Mao, Liang-fu Zhou, and Guo-dong Sui

OBJECT

Conventional methods for isocitrate dehydrogenase 1 (IDH1) detection, such as DNA sequencing and immunohistochemistry, are time- and labor-consuming and cannot be applied for intraoperative analysis. To develop a new approach for rapid analysis of IDH1 mutation from tiny tumor samples, this study used microfluidics as a method for IDH1 mutation detection.

METHODS

Forty-seven glioma tumor samples were used; IDH1 mutation status was investigated by immunohistochemistry and DNA sequencing. The microfluidic device was fabricated from polydimethylsiloxane following standard soft lithography. The immunoanalysis was conducted in the microfluidic chip. Fluorescence images of the on-chip microcolumn taken by the charge-coupled device camera were collected as the analytical results readout. Fluorescence signals were analyzed by NIS-Elements software to gather detailed information about the IDH1 concentration in the tissue samples.

RESULTS

DNA sequencing identified IDH1 R132H mutation in 33 of 47 tumor samples. The fluorescence signal for IDH1-mutant samples was 5.49 ± 1.87 compared with 3.90 ± 1.33 for wild type (p = 0.005). Thus, microfluidics was capable of distinguishing IDH1-mutant tumor samples from wild-type samples. When the cutoff value was 4.11, the sensitivity of microfluidics was 87.9% and the specificity was 64.3%.

CONCLUSIONS

This new approach was capable of analyzing IDH1 mutation status of tiny tissue samples within 30 minutes using intraoperative microsampling. This approach might also be applied for rapid pathological diagnosis of diffuse gliomas, thus guiding personalized resection.