Inhibition of LncRNA Vof-16 expression promotes nerve regeneration and functional recovery after spinal cord injury.

Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16 (lncRNA Vof-16) was upregulated after spinal cord injury, but its precise role in spinal cord injury remains unclear. Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis. PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus. The overexpression of lncRNA Vof-16 inhibited PC12 cell survival, proliferation, migration, and neurite extension, whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells. Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6, tumor necrosis factor-α, and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells. Furthermore, we established rat models of spinal cord injury using the complete transection at T10. Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury. At 7 days after spinal cord injury, rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension. At 8 weeks after spinal cord injury, rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb. Notably, lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-α and Caspase-3 expression in treated animals. Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends. These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis. The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury. The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

Corrigendum: Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA-Analysis From a Nationwide, Multicenter Registry.

[This corrects the article DOI: 10.3389/fneur.2021.720664.].

Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA-Analysis From a Nationwide, Multicenter Registry.

Background: Dl-3-n-Butylphthalide (NBP) has the potential to improve clinical outcomes in acute ischemic stroke patients by improving collateral circulation. We aimed to evaluate the efficacy and safety of NBP in patients with non-disabling minor ischemic stroke and transient ischemic attack (TIA). Methods: The BRIDGE (the observation study on clinical effectiveness of NBP on patients with non-disabling ischemic cerebrovascular disease) is a prospective registry to monitor the efficacy and safety of NBP therapy in acute non-disabling ischemic stroke or high-risk TIA. Non-disabling minor ischemic stroke patients within 48 h were enrolled across 51 stroke centers in China. We divided patients into NBP compliance or non-compliance groups according to their adherence to NBP. The primary outcome was the favorable functional outcome at 90 days, defined as a modified Rankin scale (mRS) <2. Results: Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, after adjusting for common risk factors and demographic factors, NBP-compliance group has a higher proportion of favorable functional outcome (92.1 vs. 87.4%, adjusted odds ratio 2.00, 95% confidence interval, 1.50­2.65), and a higher stroke recurrence rate (2.40 vs. 0.31%, adjusted odds ratio 8.86, 95% confidence interval, 3.37­23.30) than the NBP-non-compliance group. There was no significant difference in death and intracranial hemorrhage rate between the two groups. In subgroup analysis, patients with National Institutes of Health Stroke Scale (NIHSS) scores from 3 to 5 who complied to NBP therapy had a higher rate of favorable functional outcomes than the NBP-non-compliance group. [88.82 vs. 76.21%, adjusted odds ratio 2.52 (1.81­3.50), adjusted interaction P = 0.00]. Conclusion: In non-disabling minor ischemic stroke or TIA patients, compliance with NBP therapy led to better 90-day functional outcomes despite a higher risk of recurrence, and this effect seems to be stronger in patients with NIHSS scores of 3-5. Further large randomized, double-blind controlled studies to analyse the association between NBP and functional outcome is warranted in the coming future.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

HDAC1-mediated deacetylation of HIF1α prevents atherosclerosis progression by promoting miR-224-3p-mediated inhibition of FOSL2.

We intended to characterize functional relevance of microRNA (miR)-224-3p in endothelial cell (EC) apoptosis and reactive oxygen species (ROS) accumulation in atherosclerosis, considering also the integral involvement of histone deacetylase 1 (HDAC1)-mediated hypoxia-inducible factor-1α (HIF1α) deacetylation. The binding affinity between miR-224-3p and Fos-like antigen 2 (FOSL2) was predicted and validated. Furthermore, we manipulated miR-224-3p, FOSL2, HDAC1, and HIF1α expression in oxidized low-density lipoprotein (ox-LDL)-induced ECs, aiming to clarify their effects on cell activities, inflammation, and ROS level. Additionally, we examined the impact of miR-224-3p on aortic atherosclerotic plaque and lesions in a high-fat-diet-induced atherosclerosis model in ApoE-/- mice. Clinical atherosclerotic samples and ox-LDL-induced human aortic ECs (HAECs) exhibited low HDAC1/miR-224-3p expression and high HIF1α/FOSL2 expression. miR-224-3p repressed EC cell apoptosis, inflammatory responses, and intracellular ROS levels through targeting FOSL2. HIF1α reduced miR-224-3p expression to accelerate EC apoptosis and ROS accumulation. Moreover, HDAC1 inhibited HIF1α expression by deacetylation, which in turn enhanced miR-224-3p expression to attenuate EC apoptosis and ROS accumulation. miR-224-3p overexpression reduced atherosclerotic lesions in vivo. In summary, HDAC1 overexpression may enhance the anti-atherosclerotic and endothelial-protective effects of miR-224-3p-mediated inhibition of FOSL2 by deacetylating HIF1α, underscoring a novel therapeutic insight against experimental atherosclerosis.

8-Chloro-Adenosine Inhibits Proliferation of MDA-MB-231 and SK-BR-3 Breast Cancer Cells by Regulating ADAR1/p53 Signaling Pathway.

8-Chloro-adenosine (8-Cl-Ado) has been shown to exhibit its antitumor activity by inducing apoptosis in human lung cancer A549 and H1299 cells or autophagy in chronic lymphocytic leukemia, and MDA-MB-231 and MCF-7 breast cancer cells. Adenosine deaminases acting on RNA 1 (ADAR1) is tightly associated with cancer development and progression. The aim of this study was to investigate the role of ADAR1 in the proliferation of MDA-MB-231 and SK-BR-3 breast cancer cell lines after 8-Cl-Ado exposure and its possible mechanisms. After 8-Cl-Ado exposure, CCK-8 assay was performed to determine the cell proliferation; flow cytometry was used to analyze the cell cycle profiles and apoptosis; and the protein levels of ADAR1, p53, p21, and cyclin D1 were measured by western blotting. The results showed that the cell proliferation was greatly inhibited, G1 cell cycle was arrested, and apoptosis was induced after 8-Cl-Ado exposure. ADAR1 and cyclin D1 protein levels were dramatically decreased, while p53 and p21 levels were increased after 8-Cl-Ado exposure. Moreover, the cell growth inhibition was rescued, apoptosis was reduced, and p53 and p21 protein levels were downregulated, while cyclin D1 was upregulated when cells were transfected with plasmids expressing ADAR1 proteins. More importantly, RNA-binding domain of ADAR1 is critical to the cell growth inhibition of breast cancer cells exposed to 8-Cl-Ado. Together, 8-Cl-Ado inhibits the cell proliferation, induces G1 phase arrest and apoptosis at least by targeting ADAR1/p53/p21 signaling pathway. The findings may provide us with insights into the role of ADAR1 in breast cancer progression and help us better understand the effects of 8-Cl-Ado in the treatment of breast cancer.

HMG-CoA Reductase Inhibitors Relieve Endoplasmic Reticulum Stress by Autophagy Inhibition in Rats With Permanent Brain Ischemia.

Exploring and expanding the indications of common clinical drugs, such as statins, is important to improve the prognosis of patients with permanent cerebral infarction. It has been suggested that reversing the defects in cellular autophagy and ER stress with statin therapy may be a potential treatment option for reducing ischemic damage. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (PMCAO) by electrocoagulation surgery. Atorvastatin (ATV, 10 mg/kg/day) or vehicle was administered intraperitoneally. Rats were divided into the vehicle-treated (SHAM), ATV pretreatment for MCAO (AMCAO), and 3-methyladenine (3MA) combined with ATV pretreatment (3MAMCAO) groups. Magnetic resonance imaging, as well as immunohistochemical and Western blot assessments, were performed 24 h after MCAO. Each ATV-treated group demonstrated significant reductions in infarct volume compared with that in the vehicle-treated group at 24 h after MCAO, which was associated with autophagy reduction and ER stress attenuation in neurons and neovascularization. Next, Western blotting was used to detect the levels of the autophagy-related proteins LC3B and P62 and of ER stress pathway proteins. However, 3MA significantly partially inhibited the ER stress pathway via limiting the autophagic flux in the AMCAO group. In conclusion, our results imply that the neuroprotective function of ATV depends on autophagic activity to diminish ER stress-related cell apoptosis in rats with PMCAO and suggest that compounds that inhibit autophagic activity might reduce the neuroprotective effect of ATV after brain ischemia.

Liraglutide Ameliorates ß-Amyloid Deposits and Secondary Damage in the Ipsilateral Thalamus and Sensory Deficits After Focal Cerebral Infarction in Rats.

Focal cerebral infarction causes ß-amyloid (Aß) deposition and secondary neuronal degeneration in the ipsilateral thalamus. Thalamus is the subcortical center of sensory, the damage of thalamus could cause sensory deficits. The present study aimed to investigate the protective effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP)-1 receptor agonist, on Aß deposits and secondary damage in the ipsilateral thalamus after focal cerebral infarction. In addition, this study was conducted to investigate whether liraglutide could improve sensory function after focal cerebral infarction. Forty-two male Sprague-Dawley rats were subjected to distal middle cerebral artery occlusion (MCAO) and then randomly divided into liraglutide and vehicle groups, and 14 sham-operated rats as control. At 1 h after MCAO, rats in the liraglutide and vehicle groups were subcutaneously injected with liraglutide (100 µg/kg/d) and isopyknic vehicle, respectively, once a day for 7 days. Sensory function and secondary thalamic damage were assessed using adhesive-removal test and Nissl staining and immunostaining, respectively, at 7 days after MCAO. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling and Western blot were used to detect neuronal apoptosis. The results showed that liraglutide improved sensory deficit compared to the controls. Liraglutide treatment significantly reduced Aß deposition compared with the vehicle treatment. Liraglutide treatment decreased the neuronal loss, astroglial and microglial activation, and apoptosis compared with the vehicle treatment. Liraglutide significantly down-regulated the expression of Bcl-2 and up-regulated that of Bax in the ipsilateral thalamus compared with the vehicle group. These results suggest that liraglutide ameliorates the deposition of Aß and secondary damage in the ipsilateral thalamus, potentially contributing to improve sensory deficit after focal cerebral infarction.

Association of aquaporin­1 with tumor migration, invasion and vasculogenic mimicry in glioblastoma multiforme.

The present study aimed to assess the expression and functional role of aquaporin-1 (AQP1) in glioblastoma multiforme (GBM) migration, invasion and vasculogenic mimicry (VM). In the primary human gliomas and human glioma­derived cell lines tested, it was observed that the expression of AQP1 was upregulated. In addition, it was demonstrated that silencing of AQP1 expression resulted in decreased migration and invasion, in addition to vasculogenic mimicry in vitro. It was additionally observed that silencing of AQP1 expression resulted in in vivo inhibition of tumor growth, a decrease in the expression of invasion­associated protein, and suppression of VM formation. Based on these data, it was concluded that AQP1 may serve a role in GBM migration, invasion and VM formation, and that it may serve as a novel diagnostic/prognostic biomarker and a potential therapeutic target.

Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China): results from a prospective double-blind randomised clinical trial.

AIM: The role of clopidogrel in treating patients with acute ischaemic stroke is unclear. We have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non-cardiogenic acute ischaemic stroke. METHOD: Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China (CLASS-China) was a prospective, randomised, double-blind and placebo-controlled clinical trial in China. Patients with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were excluded. Enrolled patients were divided into two treatment groups: loading dose and routine dose. The primary outcome was the incidence of stroke recurrence or progression within 7 days. Primary safety outcome was measured by life-threatening haemorrhage. An intent-to-treat analysis was used for the statistical analysis. RESULTS: From March 2008 to March 2010, a total of 303 patients from 16 centres were recruited into this study; six were excluded because of lack of basic information. Since the enrolment was slow and the study drug expired in March 2010, this clinical trial was stopped earlier than planned. No significant baseline and demographic differences were seen between the two groups. There was no difference in primary outcome between the loading dosage group 16.1% (24/149) and control group 14.9% (22/148), respectively (p=0.782). The mortality and disability rate within 90 days in loading dose group (19.6%) was slightly lower than that in controlled group (23.4%), p=0.444. Loading dose group had two (1.3%) cases of fatal haemorrhage and control group had four (2.7%) within 90 days, p=0.674. No significant difference was detected in other adverse events between the groups. CONCLUSION: In our study stopped early due to slow enrolment, loading dose of clopidogrel does not reduce the risk of recurrent stroke. Future trials with sufficient number of patients enrolled are needed to re-examine this hypothesis.

Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.

OBJECTIVES: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1ß. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1ß, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1ß. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

MiR-223 targeting MAFB suppresses proliferation and migration of nasopharyngeal carcinoma cells.

BACKGROUND: Mounting evidence suggests that miRNAs have major functions in tumor pathogenesis, and this study aimed to identify the candidate miRNA and investigate its role in nasopharyngeal carcinoma (NPC). METHODS: MiRNA and mRNA expressions were screened by microarray assays. The cell proliferation, colony formation and migration ability were measured by MTT, soft agar and wound healing assays, respectively. The tumor growth suppression was evaluated by xenografting in nude mice. The plasma miR-223 levels in NPC patients were detected by TaqMan analysis. Real-time quantitative PCR and Western blotting were used to confirm miR-223 and MAFB expression levels. The targeting relationship between miR-223 and MAFB was verified using dual luciferase reporter assay. RESULTS: The miR-223 expression was decreased in CNE-1, CNE-2 cells as compared with NP69 cells, an immortalized human nasopharyngeal epithelial cell line, and its level also reduced in NPC patients' plasma as compared with healthy controls. Exogenous expression of miR-223 in CNE-2 cells could inhibit cell proliferation both in vitro and in vivo. Extrogenous miR-223 in CNE-2 cells would decrease the ability of colony formation and migration. MAFB, a transcription factor of Maf family members, was identified as a target gene of miR-223. We found that migration and invasion abilities were inhibited by MAFB silencing. CONCLUSIONS: MiR-223 negatively regulates the growth and migration of NPC cells via reducing MAFB expression, and this finding provides a novel insight into understanding miR-223 regulation mechanism in nasopharyngeal carcinoma tumorigenesis.

Hyperphosphorylation of tau protein in the ipsilateral thalamus after focal cortical infarction in rats.

Hyperphosphorylation of tau has been considered as an important risk factor for neurodegenerative diseases. It has been found also in the cortex after focal cerebral ischemia. The present study is aimed at investigating changes of tau protein expression in the ipsilateral thalamus remote from the primary ischemic lesion site after distal middle cerebral artery occlusion (MCAO). The number of neurons in the ventroposterior thalamic nucleus (VPN) was evaluated using Nissl staining and neuronal nuclei (NeuN) immunostaining. Total tau and phosphorylated tau at threonine 231 (p-T231-tau) and serine 199 (p-S199-tau) levels, respectively, in the thalamus were measured using immunostaining and immunoblotting. Moreover, apoptosis was detected with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay. It was found that the numbers of intact neurons and NeuN(+) cells within the ipsilateral VPN were reduced significantly compared with the sham-operated group, but the levels of p-T231-tau and p-S199-tau in the ipsilateral thalamus were increased significantly in rats subjected to ischemia for 3 days, 7 days and 28 days. Furthermore, the number of TUNEL-positive cells was increased in the ipsilateral VPN at 7 days and 28 days after MCAO. Thus, hyperphosphorylated tau protein is observed in ipsilateral thalamus after focal cerebral infarction in this study. Our findings suggest that the expression of hyperphosphorylated tau protein induced by ischemia may be associated with the secondary thalamic damage after focal cortical infarction via an apoptotic pathway.

Up-regulation of Tiam1 and Rac1 correlates with poor prognosis in hepatocellular carcinoma.

OBJECTIVE: T-cell lymphoma invasion and metastasis 1 (Tiam1) specifically activates Rho-like GTPases (e.g. Rac1) and Tiam1-Rac1 pathway affects the migration and invasion of many tumors, such as nasopharyngeal carcinoma, breast cancer and retinoblastoma. However, no studies have yet comprehensively examined the involvement of Tiam1-Rac1 pathway in hepatocellular carcinoma. In this study, we examined the relationship of the up-regulation of Tiam1 and Rac1 with clinicopathological features in patients with hepatocellular carcinoma. METHODS: Expression of Tiam1 and Rac1 was assessed in 242 hepatocellular carcinoma tissues and their adjacent normal hepatic tissues by performing immunohistochemistry and was gauged regarding stage, grade and survival. RESULTS: Immunohistochemistry showed that patients with a high clinical stage hepatocellular carcinoma (III-IV) and α-fetoprotein levels had a higher tendency to express Tiam1 and Rac1 on tumor cells than the patients with low pathologic grade hepatocellular carcinoma (I-II) (P = 0.008 and 0.01, respectively) and low α-fetoprotein levels (P = 0.006 and 0.002, respectively). In addition, Tiam1 and Rac1 up-regulation was also significantly associated with vascular invasion status (both P = 0.02), intrahepatic metastasis status (P = 0.009 and 0.01, respectively) and histological differentiation (P = 0.008 and 0.009, respectively) of patients with hepatocellular carcinoma. Moreover, post-operative survival analysis indicated that hepatocellular carcinoma patients with strong Tiam1 (P = 0.01) and Rac1 (P = 0.02) expression had shorter disease-specific survival than those with weak expression. Multivariate analysis also showed that Tiam1 and Rac1 overexpression could be two predictors of poor prognosis (P = 0.02 and 0.03, respectively). CONCLUSIONS: The current study demonstrated for the first time that the Tiam1-Rac1 pathway may play a critical role in tumor progression of hepatocellular carcinoma. The expression of Tiam1 and Rac1 can be considered as the two useful indicators for predicting the prognosis of hepatocellular carcinoma.

[The statin dosage for achieving goal of cholesterol-lowering based on risk stratification in patients with ischemic cerebrovascular diseases].

OBJECTIVE: To explore statin dosages for targeting goal of LDL-C lowering on the basis of stroke risk stratification and the dosage-effective relation of statin and LDL-C lowering in Chinese patients with ischemic stroke and transient ischemic attack (TIA). METHODS: This is a prospective and open clinical trial patients with ischemic stroke/TIA within 6 months were enrolled and the dosages of atorvastatin were calculated based on risk stratification according to "Chinese Consensus for Prevention of Ischemic Stroke/TIA with Statin" (Chinese Consensus). A dose of 10 mg of atorvastatin daily to target LDL-C goal was taken as the standard dosage targeting goal (SDTG). Patients taking this dosage of atorvastatin constituted a SDTG group. Those who needed a daily dose of 20 mg or more of atorvastatin were randomized into an intensive dosage targeting goal (IDTG) group (atorvastatin 20 - 80 mg/d) and a standard dosage non-targeting goal (SDNTG) group (atorvastatin 10 mg/d without targeting goal). All patients took atorvastatin for 12 weeks. The primary outcome was the rate of targeting goal for LDL-C lowering at 2, 4 and 12 weeks, respectively and the secondary outcome was the occurence of recurrent stroke and other vascular events within 12 weeks. The main safety endpoint was serial adverse events including symptomatic intracranial hemorrhage. RESULTS: Altogether 102 cases were enrolled and 99 cases were followed up for 12 weeks. According to the Chinese Consensus, the rate of high risk, very high risk-I and very high risk-II was 44%, 28% and 28%, respectively. Targeting rate for LDL-C lowering was 77% - 85% at each time point in the SDTG and IDTG groups, being significantly higher than those in the SDNTG group (12% - 16%, P < 0.01). No significant difference was found concerning the occurrence of recurrent stroke, other vascular events and safety endpoints among the three groups. The amplitude of LDL-C lowering was 32% - 35%, 46% - 49%, 51% - 52% and 60% - 65% with corresponding to daily dosage of 10 mg, 20 mg, 40 mg and 80 mg atorvastatin. CONCLUSIONS: At least more than half of the patients after ischemic stroke/TIA need intensive statin therapy to target the LDL-C lowering goal. The dosage-effective relation of atorvastatin and LDL-C lowering in Chinese is similar to the reported data in other races.