Objective:To investigate the neuroprotective effect of long-term prophylactic use of buphthalein on mice with permanent distal middle cerebral artery occlusion and its relationship with the nuclear factor erysid 2 related factor 2 (Nrf2) pathway.Methods:Nrf2 + /+ wild-type and Nrf2 -/- knockout mice were randomly divided into control group (equal volume vegetable oil), low-dose butylphthalide group (20 mg/kg) and high-dose butylphthalide group (60 mg/kg), with 6 mice in each group. The drug was administered once a day by gavage for 1 month, and then a permanent middle cerebral artery occlusion model was induced by electrocoagulation. After the model was made, the drug was continued and the mice were sacrificed on the 10 th day. The modified Longa grading scale and the rotating rod test were used to evaluate neurological deficits on the 3 rd and 10 th day after the model was made. After the mice were sacrificed, the cerebral infarct volume was measured by triphenyltetrazolium chloride staining. The brain water content was measured by dry and wet weight method. The expression of Nrf2 pathway related factors, including Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) were measured by quantitative real-time PCR and Western blotting. Results:On the 10 th day after modeling, compared with the Nrf2 -/- control group, the neurological deficit was significantly milder, the volume of cerebral infarction and brain water content were significantly smaller, and the mRNA and protein levels of Nrf2, HO-1 and NQO1 were significantly higher in the Nrf2 + /+ control group, and the differences were statistically significant ( P<0.05). For Nrf2 + /+ mice, compared with the control group, the cerebral infarct volume was significantly reduced ( P<0.05), the brain water content was significantly reduced ( P<0.05), and the neurological function recovery was significantly better ( P<0.05), and the levels of Nrf2, HO-1, and NQO1 mRNA and protein were significantly higher in the high-dose butylphthalide group (all P<0.05). For Nrf2 -/- mice, there were no significant differences in neurological function, cerebral infarction group volume, brain water content, Nrf2, HO-1, NQO1 mRNA and protein levels among the groups. Conclusion:Long-term butylphthalide pretreatment can significantly improve the neurological function, reduce cerebral infarction volume, reduce brain water content, and increase Nrf2, HO-1, NQO1 mRNA and protein expression levels in mice with permanent distal middle cerebral artery occlusion, suggesting butylphthalide may play a neuroprotective effect by up-regulating the expression of Nrf2 gene and its downstream antioxidant stress factors HO-1 and NQO1.

Objective To investigate the effect of high frequency (10 Hz),low frequency (1 Hz) and theta burst stimulation (TBS) mode of repetitive transcranial magnetic stimulation (rTMS) on the recovery of motor function in hemiplegic patients following acute ischemic stroke.Methods Seventy-two patients with hemiplegia after acute ischemic stroke were randomly grouped with the random number table.They were treated with low frequency (n=18),high frequency (n=18),and TBS (n=18) rTMS or sham stimulation (control group,n=18),once a day,for 2 weeks.Fugl-Meyer Assessment (FMA) and National Institutes of Health Stroke Scale (NIHSS) were used to evaluate neurological function in all patients before rTMS treatment (on the day before the first treatment) and after treatment (on the day after the last treatment).Results After treatment,the FMA and NIHSS scores in the 4 groups were significantly improved compared with before treatment (all P<0.05).After rTMS treatment,the FMA and NIHSS scores were improved significantly in the high frequency group,low frequency group and TBS group compare with the control group (all P<0.05).There were no significant differences among all the treatment groups.Conclusion sHigh frequency,low frequency and TBS rTMS can improve the recovery of motor function in hemiplegic patients following acute ischemic stroke.There were no significant differences among all the treatment modes.

Objective To study the best diagnostic imaging procedure after acute stroke.Methods 53 patients with acute stroke were recruited within 72 hours after symptom onset.CT was performed in all patients firstly, then T1 weighted-imaging( T1 WI), T2 weighted-imaging( T2WI ), gradient recalled echo T2 * weighted-imaging( GRE-T2 * WI) and diffusion-weighted imaging(DWI) were examined at 1.5T.Furthermore 15 patients with ischemic stroke received perfusion-weighted imaging(PWI) examination.Results 15 patients with acute cerebral hemorrhage and one patient of hemorrhagic brain tumor appeared clear on GRE-T2 * WI.3 patients with transient ischemic attack(TIA) were normal on T1WI ,T2WI ,GRE-T2* WI and DWI.18 cases with cerebral infarction appeared normal on GRE-T2 * WI within 6 hours after symptom onset, and 7 cases of them underwent PWI examination, the signal intensity of 3 cases were PWI ≥ DWI and of 4 cases were PWI = DWI.14 patients appeared hyperintense on GRE-T2 * WI within 6 ～72 hours after symptom onset.8 patients of them underwent PWI examination,the signal intensity of 6 cases were PWI≥DWI and of 2 cases were PWI = DWI.Of 14 patients,7 patients appeared as 1 ～ 18 dot or patchy hypointense whose diameter was about 2 ～ 5mm on GRE-T2 * WI.Another case of headache with hemiplegia and the side of the limb didnt show abnormalities on the CT, but showed a low signal in ambient cistern on T2 * WI and was proved to be subarachnoid hemorrhage.Conclusion After acute stroke,multi-sequence MRI enables the "one-stop shopping" imaging of cerebral hemorrhage,cerebral infarction and TIA in a shorter time,makes the state of micro-bleeding clear,determines ischemic penumbra,and even guides for thrombolytic treatment.

Objective To explore the mechanism of butylphthalide(NBP)in regulating microglia acti-vation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy af-ter carbon monoxide poisoning(DEACMP).Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized in-to three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegeta-ble oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-bind-ing adapter molecule 1(IBA1)was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA.Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency(P=0.001,P=0.029),reduced nerve cells(P=0.001,P=0.035),up-regulated expression of IBA1(P=0.001,P=0.042),increased mean fluorescence intensity of IBA1(P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α(TNF-α)(P=0.002,P=0.024),inter-leukin(IL)-6(P=0.001,P=0.015),and IL-1β(P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency(P=0.025),increased nerve cells(P=0.039),down-regulated expression of IBA1(P=0.035),decreased average fluorescence intensity of IBA1(P=0.031),and lowered levels of TNF-α(P=0.028),IL-6(P=0.037),and IL-1 β(P=0.034).Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cog-nitive dysfunction and brain tissue damage caused by DEACMP.

Objective To calculate the absorbed dose of ⁹⁰Y TheraSphere in the pancreas and the surrounding sensitive organs after the administration in the treatment of pancreatic cancer through the establishment of an individual voxel model, and to provide technical support for the clinical application of ⁹⁰Y TheraSphere in the treatment of pancreatic cancer. Methods An individualized voxel model was constructed in Geant4 software based on the CT images of the patient. 12 monoenergetic electron specific absorption fractions (SAFs) in the range of 0.01 to 1 MeV were calculated and validated against the ICRP data. The model and method were used to calculate the absorbed doses in the target organs under uniform and nonuniform distribution of ⁹⁰Y microspheres in the pancreas. Results The relative errors between the SAF values calculated based on the individualized voxel model and the ICRP data after mass calibration were less than 3.89%. When ⁹⁰Y was uniformly distributed in the pancreas, the absorbed dose in the pancreas was 4.69 × 10⁻⁷ Gy/Bq; the absorbed doses in the liver, kidneys, and spleen were 6.15 × 10⁻¹², 6 × 10⁻¹², and 1.65 × 10⁻¹¹ Gy/Bq, respectively. When ⁹⁰Y was distributed within the tumor, the absorbed dose in the tumor was 6.69 × 10⁻⁶ Gy/Bq and the absorbed dose in normal pancreas was 5.72 × 10⁻⁸ Gy/Bq. The fitted relationship between tumor volume V and administered activity A at the prescribed dose of 120 Gy was quadratic, with relatively low activity required for concentrated administration in the center of the tumor. Conclusion The Monte Carlo dose calculation method based on individual voxel model accurately predicted the absorbed doses in the surrounding sensitive organs (liver, kidneys, and spleen) when ⁹⁰Y TheraSphere was used to treat pancreatic cancer. These results and the analysis of the factors affecting the drug delivery activity will provide data support for the clinical research of ⁹⁰Y TheraSphere in pancreatic cancer.