Objective To investigate the influence of the chronic mountain sickness (chronic mountain sickness, CMS) on Cerebrovascular reactivity (CVR) and regulators of cerebrovascular responses. Methods Twenty-six CMS pa?tients and 23 healthy control group using transcranial Doppler ultrasound (Transcranial Doppler Ultrasoiund, TCD) as?sessment of CVR, enzyme-linked immunosorbent assay were applied to measure the serum levels of the endothelin (endo?thelin 1 , ET-1) and its receptor (endothelin receptor B, ETBR), endothelial nitric oxide synthase (endothelial nitric oxide synthase, eNOS) in CMS patients and healthy control. Results CVR (3.84 ± 3.01) was significantly lower in CMS patients than in the healthy control CVR (6.39 ± 6.87) (P <0.05); the serum concentration of ETBR in CMS patients was higher than in control [(386.07±281.57)μg/μL vs.(312.30±238.07)μg/μL] (P<0.05). Conclusions The cerebral circulation re?serve in CMS patients is significantly lower compared with healthy people. The regulation of vascular capacity by serum ET-1 and eNOS is similar between CMS patients and healthy control. The hypoxic vasodilatation in CMS patients is close?ly associated with cerebrovascular high expression of ETBR. This study may provide a scientific basis for the prevention and treatment of cerebral infarction in the patients with chronic mountain sicknes.

Objective To investigate the roles of phosphorylated glycogen synthase kinase 3β (pGSK3β) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in hypoxic preconditioning-induced neuroprotection against ischemic brain injury in rats.Methods Sixty SD rats were randomly divided into a sham operation group,a cerebral ischemia group,and a hypoxia preconditioning group (n =20 in each group).A model of middle cerebral artery occlusion (MCAO) was induced by the modified suture method.Before the preparation of MCAO model,the rats in the hypoxia preconditioning group were put into a hypobaric oxygen chamber at a simulated altitude of 5 000 m (pressure:0.53 × 105 kPa;partial pressure of oxygen:81 mmHg;1 mmHg =0.133 kPa),3 h a day for 5 days.At 24 h after MCAO modeling,the rats were subjected to neurobehavioral score (n =6) and cerebral infarction volume measurement (n =6).Immunohistochemical staining was used to detect the expression levels of neuronal nuclei (NeuN) and pGSK3β (Ser9) (n=7).Western blot was used to detect the expression levels of pGSK3 β (Ser9) and pSTAT3 (Tyr705) in the ischemic cortex (n =7).Results The neurological deficit score (1.833 ±0.408 vs.2.667 ± 0.516;t =3.101,P=0.011) and cerebral infarction volume (18.137％ ± 0.801％ vs.24.125％ ± 0.694％;t =13.840,P＜ 0.001) in the hypoxia preconditioning group were significantly lower or smaller than those in the cerebral ischemia group.Immunohistochemical staining showed that the numbers of NeuN positive cells in the cerebral ischemia group and the hypoxia preconditioning group were significantly less than that in the sham operation group (48.000 ± 1.414/high power field [HPF],124.833 ± 3.061/HPF,and 213.500 ± 2.429/HPF;F =7 150.550,P ＜ 0.001),the hypoxia preconditioning group was significantly more than the ischemia group (P ＜0.001);the numbers of pSTAT3 positive cells in the cerebral ischemia group and the hypoxia preconditioning group were significantly higher than that in the sham operation group (57.667 ± 1.366/HPF,29.167 ± 1.941/HPF and 3.500 ± 1.049/HPF;F =1 962.649,P ＜0.001),and the hypoxia preconditioning group was significantly less than the ischemia group (P ＜0.001).Western blot analysis showed that the expression levels of ischemic cortical pGSK3β and pSTAT3 in the cerebral ischemia group and the hypoxia preconditioning group were significantly higher than those of the sham operation group (pGSK3 β:2.336 ± 0.102,0.876 ± 0.196 and 0.440 ± 0.012;F =1 610.826,P ＜ 0.001;pSTAT3:8.368± 0.230,4.883± 0.123 and 0.595± 0.138;F=4018.051,P＜0.001),the hypoxia preconditioning group were significantly lower than the ischemia group (all P ＜0.001).Conclusions Hypoxia preconditioning has neuroprotective effect for ischemic brain injury in rats.It may be associated with the down-regulation of the expressions of pGSK3 and pSTAT3.

Objective To investigate the changes of the serum levels of matrix metalloproteinase- 2 (MMP-2) and peripheral blood leukocytes content and its relationship with the severity of cerebral infarction in acute cerebral in-farction(ACI)patients at different altitudes (high, middle and low). Methods One hundred thirty-nine cases and 150 healthy controls were included in the present study. Enzyme linked immunosorbent method was used to detect MMP-2 and WBC levels. Results MMP-2 levels increased as the altitude increased in controls. The MMP-2 in a descending or-der was 1.41±0.39 in Haixi (high altitude), 1.37±0.27 in Xining (middle altitude) and 1.28±0.21 in Sichuan (low altitude) (P<0.05). The serum levels of MMP-2 were significantly increased at 7 d at different altitudes (5.75±1.19, 5.23±1.12 and 4.15 ± 0.97 in low, middle and high altitudes, respectively). The WBC were significantly increased at different alti-tudes (12.93±2.11, 12.11±1.74 and 11.15±1.68 in low, middle and high altitudes, respectively) within 48 h in severe ACI group (P<0.05). MMP-2 levels in different altitudes were positively associated with the infarction size and the degree of neurological deficit, while were negatively correlated with the prognosis. The WBC in large infarction group were positive-ly correlated with the infarct size. Conclusions The levels of MMP-2 and WBC in different altitudes may be helpful in determining the ACI lesion size and the severity of the illness as well as estimating the prognosis.

Objective To investigate the neuroprotective effect of miR-181c on hypoxia-preconditioned ischemia in rats and its mechanism.Methods Thirty-nine male SD rats were randomly divided into 5 groups of control group,sham-operated group,middle cerebral artery occlusion (MCAO)group,hypoxia-preconditioned group,hypoxia-preconditioned and MCAO group.Infarct volume and behavioral deficits were quantified.Real-time PCR was applied to detect the expression levels of miR-181c and Western blotting was used to verify the target protein of mt-cox1.Results Under the treatment of hypoxia-preconditioned,the neurological impairment was alleviated and the infarct volume was reduced significantly from 22.50％ ±2.96％ to 16.40％ ±3.13 ％ (t =5.26,P ＜0.01).The expression of miR-181c was decreased significantly in hypoxia-preconditioned and MCAO group than that in MCAO group (1.89 ± 0.14 vs 3.05 ± 0.26,t =6.10,P ＜ 0.01),and the expression of mt-cox1 protein was also significantly decreased (0.54 ± 0.07 vs 0.93 ± 0.04,t =8.01,P ＜ 0.01).Conclusion Hypoxia-preconditioned may attenuate the ischemic injury in SD rats,which may be related to the down-regulation of the expression of miR-181c,therefore increasing the expression of its targeted protein mt-cox1.

AIM: To investigate the short-term efficacy and safety of sulfasalazine (SASP) 3 g per day in the treatment of patients with mild and moderate ulcerative colitis (UC). METHODS: 122 patients were treated with SASP ( 1 g, t.i.d.) for 6 weeks. The data of clinical manifestations, colonoscopic and histological involvements were compared before and after the treatment of UC. The short-period efficacy and adverse reactions were evaluated in 110 patients. RESULTS: The therapeutic project was carried out in the 110 out of 122 patients. After 110 patients were treated for 6 weeks, the clinical, colonoscopic and histological remission were 71.8%, 21.8% and 16.4%, respectively. Among the 79 patients with clinical remission, 58.2% and 67.1% of them remained grade 1 in colonoscopic and histological findings, respectively. The curative rates and the effective rates were 63.9% and 82.0%, respectively. Among the 122 patients treated with SASP, 21 of them ( 17.2%) had adverse reactions. Except 4 patients suffered urticaria and leukopenia, no patients quitted the treatment because of obvious adverse reaction. CONCLUSION: SASP ( 3 g per day) can be an effective and safe medicine in treatment of patients with mild and moderate UC, but more than half of the patients in clinical remission still have light inflammation in colonoscopy and histology.

Objective To synthesize a novel vector of chitosan-particles loaded with gadolinium (Gd-CPs) and observe the adhesion and absorption of the particles in the colon wall of mice with MR imaging in-vivo.Methods Chitosan particles (CPs) with and without gadolinium loaded were synthesized with the emulsion-droplet coalescence method.Sixteen mice were randomly classified into two groups.The suspension with Gd-CPs or with CPs was infused into the rectum of the 8 mice of each group,respectively.MR scans were performed before,during and 40 minutes after infusion for each mouse.Samples of the colon correlated to the enhanced area were obtained for electron microscopy examination.Signal intensity (SI) of ROIs in the wall of rectum or colon,muscles of the pelvis near the rectum and background were measured and corresponding relative SIs were calculated.Relative SI values between the two groups and pre- and post- infusion were compared with pared t test.Results Dimension of the Gd-CPs was about 500 nm,and content rate was about 30%. Values of relative SI of the rectum for pre- and post- infusion in the Gd-CPs group were 0.84±0.06 and 0.98±0.09(t=4.327,P＜0.01),respectively,while those in CPs group were 0.83±0.04 and 0.84±0.05(t=0.658.P＞0.05). The medial value of signal increase rate for CPs group was 19.0%.Gd-CPs particles were found inside the mucosal cells under the electron microscopy.Conclusion MR imaging in-vivo can reveal the phenomenon of adhesion and absorption of mucosa targeted chitosan particle carriers. Clinical MR imaging based on small animal coil is a good method to monitor colon mucosa targeted particle vectors in-vivo.

Objective To investigate the correlation between the apparent diffusion coefficient (ADC) and the expression of aquaporin-4 (AQP4) in brain tissue after ischemia/reperfusion in rats. Methods A model of right middle cerebral artery occlusion (MCAO) induced by suture method. Seventy Wistar rats were randomly divided into 7 groups: sham-operation (A), MCAO 30 min (B), MCAO 30 min and reperfusion 30 min (D), MCAO 30 minand reperfusion 60 min (E), MCAO 60 min (C); MCAO 60 min and reperfusion 30 min (F), and MCAO 60 min and reperfusion 60 min (G) groups (n=10 in each group). The rats in all groups underwent diffusion-weighted imaging (DWI). The relative apparent diffusion coefficient (rADC) was calculated. Triphenyltetrazolium chloride (TTC) staining was used to detect the ratio of ischemic area. Immunohistochemistry, in site hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expressions of AQP4. Results No abnormal intensity signals were observed on DWI in sham-operation group. The ranges of the high signal intensity lesions on diffusion-weighted imaging (DWI) were from small to large in groups B, C, D, E, F, and G. Then it reduced gradually, so did the ischemic area. The AQP4 expression was up-regulated significantly in groups B and E. The AQP4 expression was decreased significantly after the reperfusion in all groups. 1here was significant difference between ischemic groups and reperfusion groups (all P<0. 05). The expressions of rADC and AQP4 showed negative correlation (r=0. 72, P<0.01). Conclusions The AQP4 expression in brain tissue is closely associated with the changes of ADC after cerebral ischemia/reperfusion. DWI may indirectly reflect the levels of AQP4 expression.

Migraine is a common neurological disease.It involves complex neurological abnormalities.Recent advances in the neurophysiology of migraine have enabled us to explain some of the symptomatic problems and have contributed to the development of new targeted treatments that may change the way migraine treated in the future.Migraine treatment is individualized,in which preventive drug therapy also plays an important role.This article will discuss the new progress in the treatment of migraine,with emphasis on the new treatment of calcitonin gene-related peptide pathway.

Objective To explore glycogen synthase kinase -3β( GSK-3β) activity and Toll-like receptor 4 ( TLR4 ) proteins expression of microglia were tested in vitro experiments, and the possible mechanism of postoperative cognitive dysfunction(POCD).Methods The cell morphology of primary culture microglia was observed by inverted microscope;microglia were identified by glial fibrillary acidic protein ( GFAP ) immunofluorescence;the best POCD modeling conditions of microglia injury induced by lipopolysaccharides( LPS) were screened ; microglia vigor was assayed by MTT ; the proteins expressions of GSK-3βand TLR4 of microglia were detected by Western blot.Results GFAP immunofluorescence showed a positive result that primary culture of rat microglia was successful;MTT result showed that the best PODC modeling conditions of microglia injury induced by LPS (100 ng/mL) was 7h; Western blot results showed that the preotein expressions of GSK-3βand TLR4 of microglial cells were up-regulated by LPS compared with the control group,and there were significantly differences (P<0.01).Conclusion PODC pathogenesis may be associated with LPS that could up-regulat the protein expression of GSK-3βand TLR4 in microglial cells.

Objective To investigate the effect of seasonal and meteorological factors on the onset of stroke in Qinghai Plateau area.Methods Patients with stroke admitted to Qinghai Provincial People's Hospital from December 1,2011 to November 30,2016 were enrolled retrospectively.The meteorological data provided by Qinghai Meteorological Bureau were used to analyze the distribution of the number of cases in different seasons in Qinghai area and the relationship between the incidence of stroke and plateau meteorological factors.Results A total of 9 412 patients with acute ischemic stroke were enrolled,aged 15～95 years.There were significant statistical differences in the number of cases of ischemic stroke,cerebral hemorrhage,and subarachnoid hemorrhage in different seasons (all P ＜ 0.05).Among them,the number of cases with ischemic stroke increased first and then gradually decreased with the changes of spring,summer,fall and winter,while cerebral hemorrhage and subarachnoid hemorrhage showed a trend of decreasing first and then increasing gradually.There were significant differences in the number of cases in different relative humidity,temperature,and temperature differences (all P ＜ 0.05).Conclusion There are seasonal differences in the incidence of stroke in the plateau area,which may be associated with the influence of plateau meteorological factors.