In recent years,many investigations manifested that cortical spreading depression was probably the physiologic foundation of migraine aura.The authors reviewd the relationship between migraine aura and cortical spreading depression.

Objective To explore the effects of flunarizine hydrochloride on plasma calcitonin gene-related pep-tide and substance P levels after CSD in a rat migraine model of cortical spreading depression (CSD). Methods Thirty adult rats were randomly and evenly divided into three groups:control Group, CSD group and flunarizine group. The CSD waves were evoked by application of potassium chloride on brain surface with filter paper. Funarizine hydrochloride was intravenously administered to rats five minutes prior to application of potassium chloride. The plasma levels of CGRP and SP were measured by using radioimmunity assay. Statistical analyses were performed using two-sample t test and analy-sis of variance. Results CSD waves were absent in control group whereas CSD waves were induced in CSD and flunari-zine groups. The latency of the first CSD wave was longer in flunarizine group (167.90 ± 25.18 s) than in CSD group (130.90 ± 13.30 s) (P<0.01). The number of CSD waves was smaller in flunarizine group (4.50 ± 1.84) than in CSD group (8.50 ± 2.07) (P<0.01). The amplitude of CSD waves was lower in flunarizine group (11.40 ± 4.12 mv) than in CSD group (24.40±3.57 mv) (P<0.01). The levels of CGRP and SP in both CSD group (CGRP, 32.95±11.61 pg/mL;SP, 27.80±7.51 pg/mL) and flunarizine group (CGRP, 25.13 ± 5.67 pg/mL; SP, 19.45 ± 6.10 pg/mL) were higher than in control group (CGRP, 14.44 ± 6.39 pg/mL; SP, 12.36 ± 4.22 pg/mL) (P<0.01). The levels of CGRP and SP in flunarizine group (CGRP, 25.13±5.67 pg/mL;SP, 19.45±6.10 pg/mL) were lower than those in CSD group (CGRP, 32.95±11.61 pg/mL;SP, 27.80± 7.51 pg/mL) (P<0.05). Conclusions Flunarizine hydrochloride can inhibit CSD and reduce the plama levels of CGRP and SP in the rat model of CSD.

Objective To observe the clinical features of migraine based on out-patient clinic data and provide help for the diagnosis and treatment of migraine. Methods In a retrospective study of 309 patients with migraine, we investigated the clinical characteristics of migraine of both genders and different types, and the risk factors for MOH transformed from migraine. Results The female to male ratio was about 3:1,76.1% of the patients had triggering factors. The most common characteristics of headache were moderate to severe intensity of the pain (97.7%), aggravation by routine physical activity (75.1%), and association with nausea (90.9%) and/or vomiting (70.6%). There were significant differences in some clinical characteristics of migraine in females as compared with these in males and in patients with migraine without aura (MWOA) as compared with those with aura (MWA). The risk factors for MOH transformed from migraine were elder age of onset, high attack frequency and the analgesics frequently used (P < 0.05).Conclusion It is suggested that carefully collecting the characteristics of headache, triggering factors and therapeutic history is the foundation of correct diagnosis and effective treatment for migraine.

Objective To find the mutation of disease-causing genes of sudden unexplained death syn-drome (SU D S ) in the young by whole exome sequencing in one case. Methods O ne SU D S case was found no obvious fatal pathological changes after conventional autopsy and pathological examination. The whole exome sequencing was performed with the Ion Torrent PGMTM Systemwith hg19 as reference se-quence for sequencing data. The functions of mutations were analyzed by PhyloP, PolyPhen2 and SIFT. A three-step bioinformatics filtering procedure was carried out to identify possible significative single nu-cleotide variation (SN V ), which was missense mutation with allele frequency <1% of myocardial cell. Results Four rare suspicious pathogenic SN V were identified. C ombined with the analysis of convention-al autopsy and pathological examination, the mutation MYOM 2 (8_2054058_G/A ) was assessed as high-risk deleterious mutation by PolyPhen2 and SIFT, respectively. Conclusion Based on the second genera-tion sequencing technology, analysis of whole exome sequencing can be a newmethod for the death cause investigation of SU D S. The gene MYOM2 is a newcandidate SU D S pathogenic gene for mecha-nismresearch.

Objective To determine whether rizatriptan has an effect on cortical spreading depression (CSD) and c-Fos expression within periaqueductal grey (PAG) induced by CSD in rats. Methods The experimental SD rats were randomly divided into group A injected with KCl, group B KCl plus rizatriptan and group C NaCL The number and amplitude of CSD were recorded after KCl or NaCl injection. C-Fos positive neurons of different layer were identified by the immunohistochemical technique 2 hours after the first injection of KCl or NaCl. Results There was no CSD in group C. The number of CSD in group A ( 10.70±3.23 ) was significantly more than that in group B (6.10±2.56, t = - 3.528, P < 0.01 ). The amplitude of CSD in group A ( 17.33 (95% CI 11.45--23.11 ) mV) was significantly greater than that in group B (11.82 (95%CI 9.24--14.70) mV, Z= -4.360, P< 0.01). There were more cFos-like immnoreactive neurons in every layer in group A than in group C (P < 0.01 ) and in group B (P < 0.05 ). Conclusion Rizatriptan has an inhibitory effect on CSD, which might induce the headache through exciting the neurons in PAG.

Objective To investigate the changes of extracellular regulated protein kinases (Erk)1/2,phospho-Erk1/2,matrix metalloproteinases (MMP)-2 and MMP-9 in rats with experimental chronic fluorosis and the role of chondroitin sulfate in treatment of rat with experimental chronic fluorosis.Methods Using a group design and cell culture methods,the SH-SY5Y cells were divided into control group (culture medium with 0.0 mmol/L fluoride ion),fluoride group (fluoride ion:4.0 mmol/L) and chondroitin sulfate group (fluoride ion:4.0 mmol/L,chondroitin sulfate:0.4 g/L).The ultrastructural changes of the SH-SY5Y cells were observed through electron microscope after 24 h treatment.The SH-SY5Y cells were cultured for 72 h,the number of cells survived in three groups.were detected after stained by trypan blue.Fifteen clean grade SD rats with body weight of 100-120 g were divided into control group (tap water:fluorine content less than 0.5 mg/L),fluoride group (fluoride ion:10.0 mg/L) and chondroitin sulfate group (fluoride ion:10.0 mg/L,the rats were performed intraperitoneal injection with 0.66 mg/kg chondroitin sulfate for 5 days after intaking fluoride for 90 days) on the basis of random number table.Five rats were in each group,and the experiment was carried out for 95 days.The capability of learning and memory of rats were tested by Morris water maze test;the expression of phospho-Erk1/2,Erk1/2,MMP-2 and MMP-9 protein in brain tissue was detected by Western blotting;the expression of phospho-Erk1/2,MMP-2 and MMP-9 in hippocampus CA2 area of brain was detected by immunohistochemistry.Results More vesicles and swelling of mitochondria or endoplasmic reticulum were observed in SH-SY5Y cell treated with fluoride through electron microscope,but relatively less in chondroitin sulfate group.Survival rate and amount of SH-SY5Y treated with chondroitin sulfate [(92 ± 23)％ and (7.83 ± 1.38) × 106/ml] were significantly higher than that of fluoride group [(55 ± 2)％,(2.19 ± 1.26) × 106/ml,P ＜ 0.05].Animal experiment results showed that most rats in control group and chondroitin sulfate group used spatial direct search strategy,and the amount of this search strategy (2.20 ± 1.09,3.40 ± 1.34) was more than that in fluoride group (0.40 ± 0.54,P ＜ 0.05).The expression of phospho-Erk1/2 in brain tissue of rats in fluoride group (3.26 ± 0.88) was significantly higher than that in control group (1.53 ± 0.28) and chondroitin sulfate group (2.36 ± 0.87,P ＜ 0.05).Immunohistochemistry results showed that average gray value of phospho-Erk1/2 in chondroitin sulfate group (220.20 ± 3.09) was significantly higher than that of the control group and the fluoride group (100.00 ± 0.00,130.98 ± 1.27,P ＜ 0.05).The average gray value of MMP-2 in the fluoride group (294.52 ± 5.18) was significantly higher than that in control group and chondroitin sulfate group (100.00 ± 0.00,117.95 ± 1.55,P ＜ 0.05).The average gray value of MMP-9 protein of the fluoride group (993.64 ± 3.66) and the chondroitin sulfate group (1 167.30 ± 239) was significantly higher than that of control group (100.00 ± 0.00,P ＜ 0.05).Conclusions Erk1/2 pathway possibly maintains the stability of cell survival by regulating the expression of MMP-2 and MMP-9.Chondroitin sulfate can protective nerve cells and reduce the nervous damage caused by fluorosis to some certain extent.

Objective To explore the diagnostic value of MR elastography and diffusion?weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty?four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference(F=61.690, P<0.01). The ADC values in three groups were (1.31 ± 0.14)×10-3, (1.23 ± 0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference(F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05),(9.56±0.57),(17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non?invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

OBJECTIVE： To investigate in vitro antibacterial activity of the extracts from the root， stem and leaves of Psychotria rubra， and to investigate its mechanism of antibacterial effects. METHODS： 95％ ethanol extracts from the root， stem and leaves of P. rubra were used to prepare solution with mass concentration of 100 mg/mL （calculated by extract）. Using as penicillin sodium （0.5 mg/mL） and streptomycin sulfate （128 mg/mL） as positive control， plat stiletto method was used to determine antibacterial effects of the extracts from different parts of Staphylococcus aureus， Escherichia coli， Pseudomonas aeruginosa， Bacillus subtilis， Micrococcus luteus and Enterococcus faecalis. Using systematic solvent extraction method， the petroleum ether， ethyl acetate and n-butyl alcohol were used to extract antibacterial activity parts from P. rubra as ad to obtain the extracts of corresponding polar parts. After preparing 100 mg/mL drug solution （calculated by extract）， antibacterial effects of above 6 kinds of bacteria were investigated. The micro-broth dilution method and agar culture medium plate method were used to determine minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC）， and screen polar parts with bacteriostasis and drug-sensitive strains. Under the concentration of 0.5MIC and MIC， the growth curves of sensitive bacteria were drawn （treated for 36 h， every 4 h）； the contents of alkaline phosphatase （AKP） and soluble protein were detected in suspension （treated for 10 h， every 2 h）； bouillon culture medium instead of the extract as blank control. RESULTS： 100 mg/mL ethanol extracts from the root， stem and leaves of P. rubra showed good antibacterial effect to above 6 kinds of bacteria， in descending order as stem＞leaves＞root. Among different polar parts from the stem of P. rubra， antibacterial effect of the ethyl acetate extract was best， especially for the S. aureus， the diameter of inhibition zone reached （38.93±0.12） mm， and both MIC and MBC were 0.39 mg/mL. The ethyl acetate extract could significantly inhibit the proliferation of S. aureus， and its alkaline phosphatase and protein content in suspension were increased significantly compared with blank control （P＜0.05）. CONCLUSIONS： The stem from P. rubra is effective antibacterial parts， and exhibit good antibacterial activity to 6 kinds of common pathogens. The ethyl acetate extract from the stem of P. rubra shows strongest antibacterial effect on S. aureus， and could gradually destroy the integrity of cell wall and cell membrane.

BACKGROUNDThe molecular and cellular origins of migraine headache are among the most complex problems in contemporary neurology. Up to now the pathogenesis of migraine still remains unclearly defined. The objective of this study was to explore new factors that may be related to the mechanism of migraine.

METHODSThe present study performed a comprehensive analysis of gene expression in the trigeminal nucleus caudalis induced by electrical stimulation of dura mater surrounding the superior sagittal sinus in conscious rats using microarray analysis followed by quantitative real-time reverse-transcribed polymerase chain reaction (qRT-PCR) verification. Student's two sample t-test was employed when two groups were compared. A P value <0.05 was considered to be statistically significant.

RESULTSComparing the placebo and the electrical stimulation groups, 40 genes were determined to be significantly differentially expressed. These significantly differentially expressed genes were involved in many pathways, including transporter activity, tryptophan metabolism, G protein signaling, kinase activity, actin binding, signal transducer activity, anion transport, protein folding, enzyme inhibitor activity, coenzyme metabolism, binding, ion transport, cell adhesion, metal ion transport, oxidoreductase activity, mitochondrion function, and others. Most of the genes were involved in more than 2 pathways. Of particular interest is the up-regulation of Phactr3 and Akap5 and the down-regulation of Kdr.

CONCLUSIONThese findings may provide important clues for a better understanding of the molecular mechanism of migraine.

Animals ; Dura Mater ; physiology ; Electric Stimulation ; Gene Expression ; physiology ; Male ; Microarray Analysis ; Migraine Disorders ; genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Superior Sagittal Sinus ; physiology