Objective To study the changes of motor cortex in patients with amyotrophic lateral sclerosis(ALS)while executing sequential finger tapping movement by using blood oxygenation level dependent(BOLD)functional MRI.Methods Fifteen patients with definite or probable ALS and 15 age and gender matched normal controls were enrolled in the BOLD study,and all the subjects were right-handed with no other diseases or any recent medication history.A 3.0 T MR scanner was employed and gradient echo EPI(GRE-EPI)sequence was used to acquire the functional images.Subjects executed sequential finger tapping movement at a frequency of 1-2 Hz during a block design task.fMRI data were analyzed by using statistical parametric mapping(SPM)2.Volume of activated brain areas was compared with the use of a Student's t-test.Results Bilateral primary sensorimotor cortex(PSM),bilateral posterior aspect of premotor area(PA),bilateral supplementary motor area(SMA),contralateral inferior lateral premotor area (ILPA),bilateral parietal region(PAR),and ipsilateral cerebellum showed activation in both ALS patients and normal controls when executing the same motor task.The activation areas in bilateral PSM and bilateral posterior aspect of PA(right hand ipsilateral activation:ALS(924.5±141.1)mm3,control(829.9±98.4)mm3,P=0.05;right hand contralateral activation:ALS(9143.8±702.8)mm3,control(8638.8±506.4)mm3,P＜0.05;left hand ipsilateral activation:ALS(1162.5±357.4)mm3,control(902.5±184.2)mm3,P＜0.05;left hand contralateral activation:ALS(8255.2±870.2)mm3,control (5934.6±616.4)mm3,P＜0.05),bilateral SMA(right hand bilateral activation:ALS(6564.3±720.6)mm3,control(4710.7±416.3)mm3,P＜0.05;left hand bilateral activation:ALS(6970.5±961.8)mm3,control(3688.9±672.3)mm3,P＜0.05),and ipsilateral cerebellum(right hand ipsilateral activation:ALS(2720.0±1154.2)mm3,control(254.3±84.4)mm3,P＜0.05;left hand ipsilateral activation:ALS(4794.4±1237.0)mm3,control(1689.0±719.6)mm3,P＜0.05)were significantly larger in ALS patients than in normal controls.Extra activation areas including ipsilateral ILPA,contralateral cerebellum and bilateral posterior limb of internal capsule were only detected in ALS patients.Conclusions Similar activation areas were seen in both groups while executing the same motor task,but the activated areas were more prominent in ALS group.The increased activation areas in ALS patients may represent neural reorganization.while the extra activation areas in ALS patients may indicate functional compensation.

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.

BACKGROUND: Adriamycin is anthracycline-based drugs of anti-cancer and inhibits many malignant tumors. But due to the large toxicity, it will induce dose-dependent cardiac toxicity, resulting in heart failure in severe case. Compound huangjing oral lipid is against the injury of free radial and is expected to be applied as an assistant therapy for heart failure.OBJECTIVE: To probe into the therapeutic effect of compound huangjing oral lipid and its mechanism on heart failure.DESIGN: Randomized controlled observation was designed.SETTING: Department of Traditional Chinese Medicine , First Affiliated Hospital of Fujian University of Medical Science, Fujian College of Traditional Chinese Medicine.MATERIALS: The experiment was performed in Fujian Research Institute of Hypertension from August 2000 to May 2001, in which, 66 rats were employed and randomized into 6 groups, 11 rats in each one.METHODS: In normal group, physiological saline of equal volume was injected abdominally. In adriamycin group, adriamycin 1mg/kg was injected abdominally on the 2nd and 4th days after experiment, 2 mg/kg was injected on the 6th and 8th days, 3 mg/kg was on the 10th and 12th days and 4 mg/kg was on the 14th and 16th days. The dose was accumulated up to 20 mg/kg in 16 days. In adriamycin+compound huangjing oral liquid 2 mL (small-dose group), adriamycin +compound huangjing oral liquid 4 mL (moderate-dose group) and adriamycin+compound huangjing oral liquid 6ml (large-dose group), the oral lipid of various doses was applied for gastric perfusion everyday successively from the beginning of experiment, in which, the dose of adriamycin was same as adriamycin group. In adriamycin+tebonin group (tebonin group), tebonin 450 mg/kg was administrated once every two days, totally for 8 days, in which, the dose of adriamycin was same as adriamycin group.MAIN OUTCOME MEASURES: To observe the changes of Left ventricular weight and body weight (LVW/BW), α-MHC (myosin heavy-chain)and β-MHC.RESULTS: In the whole experiment, of 66 experimental animals, 5 rats in adriamycin group, 4 rats in small-dose group, 2 rats in moderate-dose group, 3 rats in large-dose group were died from obvious congestive heart failure, finally, 47 rats entered result analysis. Compared with normal group, in adriamycin group, α-MHC was reduced by 20.88% (P ＜ 0.01), β-MHC was increased by 50.93% (P ＜ 0.01) and LVW/BW was increased by 33.83% (P ＜ 0.01). After medication, myocardial β-MHC was transformed to α-MHC; compared with adriamycin group, α-MHC in every medical group was increased (P ＜ 0.01), β-MHC was decreased (P ＜ 0.01) and LVW/BW was decreased of different degrees (P ＜ 0.01 or P ＜ 0.05); among the above-changes, the results in moderate group were the best.CONCLUSION: Compound huangjing oral liquid alleviates toxicity of heart failure induced by adriamycin, probably due to the dose-dependence improvement of the oral liquid in myocardial α-MHC transformation.

Objective To investigate the role of the neuropsychological tests and functional imaging in differentiation between multiple system atrophy parkinsonism-predominant (MSA-P) and multiple system atrophy predominant cerebellar ataxia (MSA-C) or idiopathic Parkinson' s disease (PD).Methods We collected three groups of patients including MSA-P (n =8),MSA-C (n =13),idiopathic PD (n =13),and control group (n =13) between December 2012 and November 2013 in General Hospital of People's Liberation Army.We then compared the scores of neuropsychological assessment and parameters obtained from diffusion tensor imaging (DTI) examination among the four groups.Results (1) MSA-P group had longer time-consuming of trail-making test((103.7 ± 25.9) s) and lower graphic symbol test scores (20.9 ±6.1) than that of the MSA-P group ((80.9 ± 29.1) s ; 28.1 ± 7.4) and PD group ((72.0 ± 19.6) s ;29.0 ± 9.4 ; all P ＜ 0.05).(2) Mean diffusivity (MD) in both putamen (8.01 ± 0.76,7.91 ± 0.74) and the left substantia nigra (8.31 ± 0.43),thalamus (8.30 ± 0.69),external capsule (8.12 ± 0.32) of MSA-P group was significantly different from that of MSA-C group (7.27 ± 0.42,7.34 ± 0.3 1,7.58 ±0.81,7.81 ±0.34,7.70 ±0.44) and PD group (7.35 ±0.43,7.45 ±0.43,7.66 ±0.45,7.72 ±0.40,7.56 ± 0.37) ; Significantly higher MD in both middle cerebellar peduncle (8.54 ± 0.74,8.28 ± 0.71),medulla oblongata (8.32 ± 0.61) was demonstrated in MSA-C group than that of MSA-P group (8.54 ±0.74,8.28 ±0.71,8.32 ±0.61),PD group (7.25 ±0.70,7.30 ±0.66,7.65 ±0.50) and control group (6.94±0.39,7.08 ±0.32,7.44 ±0.41; all P＜0.01).(3) Fractional anisotropy (FA) in the left external capsule (0.45 ± 0.35) and right thalamus (0.28 ± 0.27),occipital lobe (0.47 ± 0.87) in MSA-P group was significantly different from that in MSA-C group (0.48 ± 0.36,0.23 ± 0.24,0.49 ± 0.49 ; P ＜0.05) ; FA in the left occipital lobe (0.46 ± 0.10) in PD group was significantly different from that in MSAP group (0.56 ± 0.82 ; P ＜ 0.01).Conclusion Trail-making test,graphic symbol test and DTI can be used to differentiate MSA-P type from MSA-C type or PD.

OBJECTIVETo investigate the magnetic resonance (MR) features of meningeal carcinomatosis, and to improve the ability in understanding and diagnosing meningeal carcinomatosis by MR findings.

METHODSEleven cases with proven meningeal carcinomatosis were studied by conventional and Gd-DTPA enhanced MR imaging. The enhancement patterns and features, as well as the types of meningeal involvement, were retrospectively analyzed.

RESULTSConventional MR imaging showed no evident meningeal abnormalities. After the administration of Gd-DTPA, abnormal pia mater enhancement was detected in 9 cases, demonstrating as the continuous, thin, and lineal high signal intensity on the brain surface that could descend into the sulci. The abnormal pial enhancement occurred on the cortical surfaces of cerebellum, brainstem, and cerebrum. No abnormal enhancement in the subarachnoid space was found. Abnormal dura-arachnoid enhancement was seen in 3 cases, showing as the continuous, thick, and curvilineal high signal intensity over the convexities or in the tentorium without extension into the cortical sulci. Cerebral dura-arachnoid involvement was found in all 3 cases and one of them also showed abnormal enhancement in cerebellar dura-arachnoid and tentorium. Of the 11 cases, 9 with pial involvement had abnormal cerebrospinal fluid (CSF) results, 2 involving only the dura-arachnoid had normal CSF results.

CONCLUSIONMeningeal carcinomatosis could be well demonstrated by Gd-DTPA enhanced MR imaging, and its type could be differentiated by the enhancement features. Combined with the clinical information, Gd-enhanced MR imaging may lead to the diagnosis and guide the therapy of meningeal carcinomatosis.

Adolescent ; Adult ; Aged ; Breast Neoplasms ; pathology ; Child ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement ; Lung Neoplasms ; pathology ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms ; diagnosis ; secondary ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Retrospective Studies ; Spinal Cord Neoplasms ; diagnosis ; secondary

OBJECTIVE: The periaqueductal gray matter (PAG), a small midbrain structure, presents dysfunction in migraine. However, the precise neurological mechanism is still not well understood. Herein, the aim of this study was to investigate the texture characteristics of altered PAG in episodic migraine (EM) patients based on high resolution brain structural magnetic resonance (MR) images. MATERIALS AND METHODS: The brain structural MR images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) patients using a 3T MR system. A PAG template was created using the International Consortium Brain Mapping 152 gray matter model, and the individual PAG segment was developed by applying the deformation field from the structural image segment to the PAG template. A grey level co-occurrence matrix was used to calculate the texture parameters including the angular second moment (ASM), contrast, correlation, inverse difference moment (IDM) and entropy. RESULTS: There was a significant difference for ASM, IDM and entropy in the EM group (998.629 ± 0.162 × 10−3, 999.311 ± 0.073 × 10−3, 916.354 ± 0.947 × 10−5) compared to that found in the NC group (998.760 ± 0.110 × 10−3, 999.358 ± 0.037 × 10−3 and 841.198 ± 0.575 × 10−5) (p < 0.05). The entropy was significantly lower among the patients with CM (864.116 ± 0.571 × 10−5) than that found among patients with EM (p < 0.05). The area under the receiver operating characteristic curve was 0.776 and 0.750 for ASM and entropy in the distinction of the EM from NC groups, respectively. ASM was negatively related to disease duration (DD) and the Migraine Disability Assessment Scale (MIDAS) scores in the EM group, and entropy was positively related to DD and MIDAS in the EM group (p < 0.05). CONCLUSION: The present study identified altered MR image texture characteristics of the PAG in EM. The identified texture characteristics could be considered as imaging biomarkers for EM.
Biomarkers ; Brain ; Brain Mapping ; Entropy ; Gray Matter ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Migraine Disorders ; Periaqueductal Gray ; ROC Curve

BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

OBJECTIVE： To compare inhibitory effects of ethanol extract of different medicinal parts （root， stem， leaf， seed， flower and flesh） from Syzygium jambos on the activities of α-glycosidase and α-amylase. METHODS： Using half-inhibitory concentration value （IC50） as evaluation index， acarbose as positive control， inhibitory effects of ethanol extract of different medicinal parts from S. jambos on the activities of α-glycosidase （from yeast and small instestine in mice） and α-amylase were evaluated with in vitro inhibition model. The enzymatic dynamics and Lineweaver-Burk methods were used to analyze the inhibitory type of the best medicinal part on the activities of α-glycosidase and α-amylase. RESULTS： In the yeast α-glucosidase inhibitory activity test， the order of inhibitory activity was S. jambos seed＞S. jambos stem＞S. jambos leaf＞S. jambos root＞S. jambos flower＞S. jambos flesh＞acarbose. In the mice intestine α-glucosidase inhibitory activity test， the order of inhibitory activity was S. jambos seed＞S. jambos stem＞S. jambos root＞S. jambos leaf＞S. jambos flower＞S. jambos flesh＞acarbose. In the α-amylase inhibitory activity test， the order of inhibitory activity was acarbose＞S. jambos seed＞S. jambos stem＞S. jambos root＞S. jambos leaf＞S. jambos flesh＞S. jambos flower. Ethanol extract of S. jambos seed had the stronger inhibition activity against α-glucosidase from yeast，α-glucosidase from small intestine in mice and α-amylase than other medicinal parts [IC50 were（6.64±0.24）， （32.77±2.46） and （41.18±1.63） μg/mL]. Ethanol extract of S. jambos seed had the stronger inhibition activity against α-glucosidase than acarbose [IC50 to α-glucosidase from yeast and α-glucosidase from small intestine in mice were （2 833.33±5.48）， （1 304.21±6.45） μg/mL] （P＜0.05）. The inhibitory effect of ethanol extract from S. jambos on the activity of α-amylase was less than that of acarbose [IC50 was （27.27±1.24） μg/mL] （P＜0.05）. Enzymatic dynamics showed that the inhibitory type of ethanol extract from S. jambos seed on α-glucosidase and α-amylase were both reversible competitive inhibition. CONCLUSIONS： Among different parts of S. jambos such as root， stem， leaf， seed， flower and flesh， S. jambos seed shows the strongest inhibitory effects on the activities of α-glucosidase and α-amylase， which has the value of being developed for the treatment of diabetes or health food.