Publications by authors named "Ze-Bin Chen"

13 Publications

  • Page 1 of 1

Phragmunis a suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Neurochem Int 2021 Jul 9;147:105051. Epub 2021 May 9.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen, 518035, China. Electronic address:

Glioblastoma (GBM) is a highly aggressive brain tumor. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Studies investigating the mechanism revealed that PGA diminished the binding efficiency of ETS family of transcription factor (ELK1) and Serum response factor (SRF), and suppressed ELK1-SRF complex-dependent transcription, which decreased the transcriptional levels of downstream genes Early growth response protein 1 (EGR1)-Polycomb ring finger (BMI1), thus inducing the imbalanced regulation between Myeloid cell leukaemia-1 (MCL1) and F-Box and WD repeat domain containing 7 (FBXW7). Finally, orthotopic xenograft models were established to confirm the anti-glioma effect of PGA on tumour growth. We showed, for the first time, that the cytotoxic effects of PGA occurred by inducing MCL1 inhibition and FBXW7 activation by blocking ELK1-SRF complex-dependent transcription. The blockage of ELK1-mediated transcription resulted in the suppression of EGR1-BMI1, which led to the upregulation of FBXW7 expression and downregulation of MCL1. These findings suggested that PGA could be a therapeutic drug candidate for the treatment of recurrent GBM by targeting the ELK1-SRF complex.
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July 2021

Machine learning to predict high-dose methotrexate-related neutropenia and fever in children with B-cell acute lymphoblastic leukemia.

Leuk Lymphoma 2021 Apr 26:1-12. Epub 2021 Apr 26.

Department of Hematology/Oncology, Shenzhen Children's Hospital, Shenzhen, People's Republic of China.

Methotrexate (MTX), an antimetabolite for the treatment of leukemia, could cause neutropenia and subsequently fever, which might lead to treatment delay and affect prognosis. Here, we aimed to predict neutropenia and fever related to high-dose MTX using artificial intelligence. This study included 139 pediatric patients newly diagnosed with standard- or intermediate risk B-cell acute lymphoblastic leukemia. Fifty-seven SNPs of 16 genes were genotyped. Univariate and multivariate analysis were used to select SNPs and clinical covariates for model developing. Five machine learning algorithms combined with four resampling techniques were used to build optimal predictive model. The combination of random forest with adaptive synthetic appeared to be the best model for neutropenia (sensitivity = 0.935, specificity = 0.920, AUC = 0.927) and performed best for fever (sensitivity = 0.818, specificity = 0.924, AUC = 0.870). By machine learning, we have developed and validated comprehensive models to predict the risk of neutropenia and fever. Such models may be helpful for medical oncologists in quick decision-making.
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April 2021

[Electroacupuncture preconditioning alleviates kidney injury in hyperglycemic mice].

Zhen Ci Yan Jiu 2021 Mar;46(3):215-20

Clinical Skills Training Center, Hubei University of Chinese Medicine, Wuhan 430000, China.

Objective: To explore the protective effect and molecular mechanism of electroacupuncture (EA) preconditioning on renal injury induced by streptozotocin (STZ) in hyperglycemic mice.

Methods: Eighty male C57BL/6 mice were randomly divided into 4 groups: control, model, EA and sham EA groups, =20 in each group. The hyperglycemic model was established by intraperitoneal injection of 0.1% STZ solution (50 mg/kg) for 5 days. EA preconditioning or sham EA was applied at "Zusanli" (ST36) and "Shenshu" (BL23), once daily for 7 successive days in the EA or sham EA group. Three days after mode-ling, the blood glucose was measured after fasting for 6 hours. The degree of renal injury was observed by HE staining and PAS staining; the expressions of transient receptor potential cation channel 6 (TRPC6) and Nephrin protein in glomerulus were observed by immunohistochemistry; the expressions of TRPC6 and Nephrin protein in renal cortex were detected by Western blot.

Results: Compared with the control group, the blood glucose level was significantly increased (<0.01), the glomerular cross-sectional area was apparently increased (<0.000 1), the glomerular capillaries dilated, the matrix proliferated, the brush edge of renal tubules disappeared, the proportion of abnormal renal tubules increased (<0.000 1), and the expressions of TRPC6 and Nephrin in glomeruli and renal tissue were significantly increased (<0.01) in the model group. Following EA treatment and compared with the model and sham EA groups, the blood glucose was significantly down-regulated (<0.01), the renal tissue injury was apparently alleviate, the cross-sectional area of glomerulus was reduced (<0.05), the brush edge of renal tubules changes were obviously improved, the proportion of abnormal renal tubules decreased (<0.000 1), and the expressions of TRPC6 and Nephrin in glomerulus and renal tissue decreased (<0.05) in the EA group.

Conclusion: EA preconditioning can alleviate renal injury in hyperglycemic mice, which is closely related to its effects in reducing renal TRPC6 and Nephrin expressions and inhibiting podocyte activation.
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March 2021

The presence of microvascular invasion guides treatment strategy in recurrent HBV-related HCC.

Eur Radiol 2020 Jun 11;30(6):3473-3485. Epub 2020 Feb 11.

Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Objectives: We used the status of microvascular invasion (MVI) at primary resection to help treatment selection for hepatitis B virus-positive (HBV+) recurrent hepatocellular carcinoma (rHCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B-C.

Methods: From 2009 to 2017, we enrolled 221 consecutive HBV+ rHCC patients at BCLC stage B-C who underwent re-resection (RR), radiofrequency ablation (RFA), or transarterial chemoembolization (TACE). Post recurrence survival (PRS) and overall survival (OS) were compared between RR/RFA and TACE according to MVI status. A one-to-one propensity score matching analysis was performed.

Results: For MVI(-) patients, the median PRS was 62.3 months for the RR/RFA group and 21.1 months for the TACE group (p = 0.039). The corresponding OS was 71.4 months and 26.6 months, respectively (p = 0.010). For MVI(+) patients, the median PRS in the RR/RFA group and TACE group was 14.7 months and 10.1 months (p = 0.115). The corresponding OS was 23.4 months and 16.4 months, respectively (p = 0.067). After matching, the dominance of RR/RFA over TACE remained in MVI(-) patients for both PRS (62.3 months vs 15.3 months, p = 0.019) and OS (98.1 months vs 33.4 months, p = 0.046). No significant difference was found in MVI(+) patients for either PRS (14.7 months vs 11.8 months, p = 0.593) or OS (23.4 months vs 28.1 months, p = 0.662).

Conclusions: MVI status definitely helps select treatment options in HBV+ rHCC patients. For MVI(-) patients, RR/RFA provided better survival than TACE while for MVI(+) patients, TACE shared similar survival outcomes.

Key Points: • This study aimed at the determination of the optimal treatment options (ablation /resection vs TACE) in case of recurrent HBV-related HCC. • It showed that MVI status, established at primary resection of HCC, was a powerful marker for selecting the best treatment option in these patients. • In MVI(-) patients, RR/RFA achieved a better survival than TACE. In MVI(+) patients, TACE shared similar survival.
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June 2020

Treatment selection of recurrent hepatocellular carcinoma with microvascular invasion at the initial hepatectomy.

Am J Transl Res 2019 15;11(3):1864-1875. Epub 2019 Mar 15.

Department of Medical Imaging, Sun Yat-sen University Cancer Center 651 Dongfeng Road East, Guangzhou, China.

Background: Recurrent hepatocellular carcinoma (rHCC) patients with microvascular invasive (MVI) positive at first resection usually had poorly differentiated tumors and worse survivals. The optimal treatment for this population remains to be elucidated.

Methods: We retrospectively analyzed 319 rHCC patients with MVI-positive at first resection from June, 2009 to June, 2017. Survival and costs between curative treatments [re-resection (RR) and radiofrequency ablation (RFA)] and transarterial chemoembolization (TACE) were compared. Subgroup comparisons were made in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0-A and BCLC stage B-C, respectively. A one-to-one propensity score matching (PSM) was used to diminish bias.

Results: In BCLC stage 0-A, 98 received RR/RFA, and 49 received TACE. The median overall survival (OS) of RR/RFA group was not reached, while the OS of TACE group was 26.3 months (=0.001). After matching, the OS of the RR/RFA group was longer than that of the TACE group (39.5 vs. 26.3 months, =0.045). In BCLC stage B-C, 137 patients received TACE, 11 received RR and 24 received RFA. The median OS was 29.8 months, 17.9 months and 11.1 months for RR, RFA and TACE group, respectively. No significant difference was found between RR and TACE (=0.237) or RFA and TACE (=0.484) after matching. Costs of the TACE group was significantly lower than that of the RR group but similar to that of the RFA group.

Conclusion: RR/RFA provided better survival outcomes for rHCC patients with MVI-positive at first resection in selected BCLC stage 0-A. In selected BCLC stage B-C, TACE shared a similar efficacy with RR and RFA but a lower cost than RR.
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March 2019

Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI.

Eur Radiol 2019 Sep 28;29(9):4648-4659. Epub 2019 Jan 28.

Department of Medical Ultrasonics, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objectives: Preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular cancer (HCC) is important for surgery strategy making. We aimed to develop and validate a combined intratumoural and peritumoural radiomics model based on gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in primary HCC patients.

Methods: This study included a training cohort of 110 HCC patients and a validating cohort of 50 HCC patients. All the patients underwent preoperative Gd-EOB-DTPA-enhanced MRI examination and curative hepatectomy. The volumes of interest (VOIs) around the hepatic lesions including intratumoural and peritumoural regions were manually delineated in the hepatobiliary phase of MRI images, from which quantitative features were extracted and analysed. In the training cohort, machine-learning method was applied for dimensionality reduction and selection of the extracted features.

Results: The proportion of MVI-positive patients was 38.2% and 40.0% in the training and validation cohort, respectively. Supervised machine learning selected ten features to establish a predictive model for MVI. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the combined intratumoural and peritumoural radiomics model in the training and validation cohort were 0.85 (95% confidence interval (CI), 0.77-0.93), 88.2%, 76.2%, and 0.83 (95% CI, 0.71-0.95), 90.0%, 75.0%, respectively.

Conclusions: We evaluate quantitative Gd-EOB-DTPA-enhanced MRI image features of both intratumoural and peritumoural regions and provide an effective radiomics-based model for the prediction of MVI in HCC patients, and may therefore help clinicians make precise decisions regarding treatment before the surgery.

Key Points: • An effective radiomics model for prediction of microvascular invasion in HCC patients is established. • The radiomics model is superior to the radiologist in prediction of MVI. • The radiomics model can help clinicians in pretreatment decision making.
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September 2019

[Comparison of Protective Effect of Electroacupuncture on Myocardial Ischemia Injury Between Different Acupoint Formulas in Rats].

Zhen Ci Yan Jiu 2017 Apr;42(2):131-5

Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan 430061, China.

Objective: To observe the different effects of electroacupucnture of "Neiguan" (PC 6) grouping with other acupoints on myocardial ischemia (MI) injury, so as to provide evidence for clinical acupoint formulas.

Methods: Forty Wistar male rats were randomly divided into normal, model, EA 1[bilateral "Neiguan" (PC 6), bilateral "Zusanli" (ST 36),"Guanyuan" (CV 4)], and EA 2[bilateral "Neiguan" (PC 6), bilateral "Shenmen" (HT 7), "Danzhong" (CV 17)] groups, 10 rats in each group. The MI model was established by subcutaneous injection with ISO solution(5 mL/kg), once per day for 7 days. Both EA 1 and EA 2 groups were subjected to EA (2 Hz/100 Hz, 1 mA) for 10 min before subcutaneous injection, once daily for 21 days. Electrocardiogram (ECG) was recorded after treatment. Serum cTnT was detected by biochemistry. SOD, GSH-Px and MDA in myocardial tissues of left ventricular were measured by ELISA, and the ultrastructural changes of myocardial cells in the left ventricular were observed by electron microscope.

Results: Compared with the normal group, the amplitude of S-T segment and HR of ECG, cTnT and MDA contents were significantly increased in the model group (<0.01) accompanied with seriously destroyed ultrastructure in the myocardial tissue, while SOD and GSH-Px levels were lower than those in the normal group (<0.01). However, EA treatments reversed all the abnormal changes in the model group (<0.05). There was no significant difference between EA 1 and EA 2 groups in the amplitude of S-T segment and HR (>0.05); cTnT and MDA levels in the EA 1 group were lower than those in the EA 2 group (<0.05), while SOD and GSH-Px levels were higher than those in the EA 2 group (<0.05), accompanied with lighter degree of ultrastructure damage in the myocardial tissue in the EA 1 group.

Conclusions: EA can prevent myocardial ischemic injury, and the effect of EA 1 treatment was better than that of EA 2.
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April 2017

High-Tech Acupuncture for Prevention of Lifestyle Diseases-A Sino-Austrian Cooperation Research Protocol on Heart Rate Variability.

Chin J Integr Med 2018 Jun 20;24(6):423-428. Epub 2017 Jun 20.

College of Acupuncture and Orthopaedics, Hubei University of Chinese Medicine, Wuhan, 430061, China.

Background: Acupuncture can not only be used for well-known diseases, but also for so-called modern lifestyle-related diseases. Using innovative methods like e.g. new analyses of heart rate variability (HRV), it is also possible to investigate diseases like burnout syndrome, ie., qi deficiency in Chinese medicine (CM).

Objective: The main object of this research protocol is to perform research on the relationship of burnout syndrome and heart rate (HR) and HRV.

Methods: A total of 175 patients with burnout syndrome (qi deficiency syndrome) in five groups and 35 healthy volunteers will be investigated. Based on random numbers generated by computer and concealed in opaque envelops, the patients will be assigned to four acupuncture groups using Zusanli (ST 36) acupuncture stimulation, Guanyuan (CV4) acupuncture stimulation, both points, and both points with Streitberger device respectively, and a moxibustion group using both points mentioned above, with 35 cases in each group. Altogether four different experiments are planned. Experiment 1 includes 70 subjects and is a comparison between a burnout group and a control group (healthy volunteers). The evaluation parameters are different scores and indices of HR and HRV. Experiment 2 includes 140 subjects and compares the efficacy of different acupuncture points. In experiment 3 (105 subjects), acupuncture and moxibustion should be compared to healthy volunteers. Experiment 4 (70 subjects) investigates the long-term therapeutic effects of acupuncture and moxibustion on the scores of qi deficiency and HR/HRV in qi deficiency patients. In both the acupuncture and moxibustion groups, a total of 10 treatments will be performed.

Conclusions: The joint research aims at the scientific evaluation of CM, mainly in the field of HRV. This parameter could be a very good indicator of the state of health and can be inflfluenced by different acupuncture methods, as shown in the past.
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June 2018

PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P.

Cancer Lett 2016 06 29;376(1):148-54. Epub 2016 Mar 29.

Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhong Shan 2nd Road, Guangzhou 510080, China. Electronic address:

Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer.
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June 2016

Puerarin Ameliorates D-Galactose Induced Enhanced Hippocampal Neurogenesis and Tau Hyperphosphorylation in Rat Brain.

J Alzheimers Dis 2016 ;51(2):605-17

Department of Anatomy and Histology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.

Enhanced neurogenesis has been reported in the hippocampus of patients with Alzheimer's disease (AD), the most common neurodegenerative disorder characterized with amyloid-β (Aβ) aggregation, tau hyperphosphorylation, and progressive neuronal loss. Previously we reported that tau phosphorylation played an essential role in adult hippocampal neurogenesis, and activation of glycogen synthase kinase (GSK-3), a crucial tau kinase, could induce increased hippocampal neurogenesis. In the present study, we found that treatment of D-galactose rats with Puerarin could significantly improve behavioral performance and ameliorate the enhanced neurogenesis and microtubule-associated protein tau hyperphosphorylation in the hippocampus of D-galactose rat brains. FGF-2/GSK-3 signaling pathway might be involved in the effects of Puerarin on hippocampal neurogenesis and tau hyperphosphorylation. Our finding provides primary in vivo evidence that Puerarin can attenuate AD-like enhanced hippocampal neurogenesis and tau hyperphosphorylation. Our finding also suggests Puerarin can be served as a treatment for age-related neurodegenerative disorders, such as AD.
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December 2016

[Effects of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy].

Zhongguo Zhen Jiu 2012 Feb;32(2):145-8

College of Acupuncture and Orthopedics, Hubei University of CM, Wuhan 430061, China.

Objective: To discuss the mechanisms of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy.

Methods: Forty SD rats were randomly divided into four groups: a normal group, a model group, a model plus p38 MAPK inhibitor group, a model plus electroacupuncture group, ten rats in each group. The model rats were established by subcutaneous injection 3 mg/(kg x d) of Isoprenaline Hydrochloride; model plus p38 MAPK inhibitor group were injected 0.3 mg/(kg x d) of specific inhibitor SB 203580; model plus electroacupuncture group was treated by electroacupuncture at "Neiguan"(PC 6) with continuous-wave, 2 Hz and 1 mA for 20 minutes, once a day for 14 days. There was no treatment in other two groups. The contents of TNF-alpha and IL-1beta in heart tissue were detected by radioimmunoassay and the p38 MAPK, p-p38 MAPK by western blot.

Results: Compared with normal group, the contents of TNF-alpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly increased in model group (all P < 0.01). The contents of TNFalpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly decreased in model plus p38 MAPK inhibitor group and model plus electroacupuncture group, compared with model group, all P < 0.05; compared with normal group, P < 0.05, P < 0.01; but no significant difference between model plus p38 MAPK inhibitor group and model plus electroacupuncture group (P > 0.05).

Conclusion: Electroacupuncture at "Neiguan" (PC 6) can prevent the phosphorylation of p38 MAPK of myocardial hypertrophy, and the mechanism maybe adjust p38 MAPK signaling pathway by inhibiting the expression of TNF-alpha and IL-1beta.
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February 2012

[Influence of electroacupuncture of Guanyuan (GV 4) and Zusanli (ST 36) on the immune function of T cells in aging rats].

Zhen Ci Yan Jiu 2009 Aug;34(4):242-7

College of Acu-moxibution, Orthopedics and Traumatology, Hubei College of Chinese Medicine, Wuhan 430061, China.

Objective: To observe the influence of electroacupuncture (EA) on T cell immunologic function in the aged rats so as to reveal its underlying mechanism in anti-aging effect.

Methods: Fifty SD rats (half male and half female) were randomly divided into normal control (young rats), aging model (model), EA group, immunosuppression (IS), and EA+ IS groups. Aging model (in the late 4 groups) was duplicated by subcutaneous injection of D-galactose for 40 days. Guanyuan (CV 4) and bilateral Zusanli (ST 36) were punctured and stimulated electrically (2 Hz, 1 mA), 15 min every time, six times a week and for four weeks. IS model was induced by i. p. i. of cytoxan (60 mg/kg) after 26 and 27 days' EA treatment. Splenetic T lymphocyte proliferation index was assayed by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) chromatometry. IL-2/IL-2 receptor (R) expression level of T cells was measured by enzyme linked immunosorbent assay (ELISA). CD8+ CD28(+) -T cell subset fluorescence intensity was detected by flow cytometry.

Results: Compared with normal control group, the splenetic T lymphocyte proliferation index, IL-2 and IL-2R expression levels, and CD8+ CD28(+) -T cell density in model and IS groups decreased significantly (P < 0.01). In comparison with model group, the abovementioned indexes in EA and EA + IS groups increased significantly (P < 0.01), and those indexes levels of EA + IS group were also significantly higher than those in IS group ( P < 0.05, P < 0.01). Comparison between EA and EA+ IS groups showed that CD8+ CD2+ T cell expression of the later group was significantly lower than that in EA group (P < 0 05). No significant differences were found between EA and EA + IS groups in T cell proliferation rate and IL-2 and IL-2R expression levels (P > 0.05)

Conclusion: EA of CV 4 and ST 36 induced upregulation of T cell proliferation and IL-2/IL-2R, and CD8+ CD(+)28 -T cell may contribute to its antiaging and immuno-enhancement effects in the aged rats.
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August 2009

[Effect of acupuncture on expression of neurology-related genes in the brain tissue of the rat].

Zhongguo Zhen Jiu 2005 Aug;25(8):573-6

Hubei TCM College, Wuhan, China.

Objective: To analyze and explore the molecular mechanism of acupuncture precondition (AP) in improving brain ischemia reperfusion injury.

Methods: Six male Wistar rats were divided into a normal group of 3 rats and an acupuncture group of 3 rats. In the acupuncture group, acupuncture precondition was first given at "Shenshu" (BL 23) and "Baihui" (GV 20). The brain of the rat was removed 0.5 hour after the needle was withdrawn, and then gene differential expression was analyzed by genechip method.

Results: After acupuncture precondition for 0.5 h, expression of 265 genes showed changes of more than 2 times, and that of 20 genes had a significant difference as compared with that of the normal rat (P<0.05). Among the genes, expression of 8 was upregulated and 12 downregulated; 11 were related with neuron signal conduction (ion channel, transmitter, receptor, second message), 5 with gene transcription and control, 2 with metabolism enzyme, 1 with heat shock reaction and 1 with cell skeleton.

Conclusion: Some gene expression substances induced by acupuncture play an important role in AP resisting brain ischemia reperfusion injury; and functional changes of neurons after AP are possibly the important basis of its subsequent action in resisting brain ischemia reperfusion injury.
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August 2005