Objective To detect the change of cerebral perfusion in pediatric patients with Leigh's syndrome (LS)by using MR perfusion technique.Methods Twelve patients with Leigh's syndrome and thirteen normal children were scanned with the sequence of flow-sensitive alternating inversion recovery exempting separate T_1 measurement (FAIREST).Their relative cerebral blood flow(rCBF)values were obtained in regions of bilateral basilar nuclei and bilateral thalami.Student t-test was used to compare them between the two groups and receiver operating characteristic(ROC)curve analysis was carried out.Results Statistical analysis revealed significant difference between two groups in the regions of bilateral basilar nuclei and right thalamus(t =3.26,P =0.002;t =2.25 ,P =0.018 ;t =2.88 ,P =0.004,respectively).The rCBF values for LS group and control group were 0.432?0.158 and 0.619?0.125 for right basilar nuclear, 0.478?0.186 and 0.621?0.123 for left basilar nuclear,0.630?0.189 and 0.833?0.160 for right thalamus,respectively.The areas under the ROC curves were 0.833 and 0.756 for the rCBF of right and left basilar nuclear,respectively.Conclusion Relative CBF maps may reveal changes of cerebral blood flow in some specific brain regions in patients with Leigh's syndrome.It can provide additional information to the clinicians in the evaluation of the disease.

AIM: To assess the relative agreement of GAT and NCT in IOP measurement by comparing the differences between Goldmann applanation tonometer (GAT) and non-contact tonometer (NCT) in intraocular pressure (IOP) detection.METHODS: IOP of 529 eyes of 265 volunteers were measured with both NCT and GAT, respectively.RESULTS: The measurement results of NCT were lower than that of GAT, there was significant difference between the IOP measured with NCT and GAT (19.13 vs23.43, t=22.644, P＜0.05). With the increasing of IOP values, the difference magnitude was greater, especially in IOP group that was more than 30mmHg, but the correlation coefficient became lower.CONCLUSION: The measurement results with NCT are lower than that of GAT. When the IOP with the NCT is in borderline value, it need be corrected with GAT, in order to discover the pathologically elevated IOP and avoid the misdiagnosis and mistreatment of glaucoma.

This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
Animals ; Antihypertensive Agents ; chemistry ; pharmacology ; Calcium Channel Blockers ; chemistry ; pharmacology ; Calcium Channels, L-Type ; genetics ; metabolism ; Drug Repositioning ; methods ; Molecular Structure ; Myocardium ; metabolism ; Rabbits

OBJECTIVEThe aim of this investigation was to study the expression of collagen type II in the cartilage of mandibular condyle following asymmetric inter-maxillary traction.

METHODSTwo hundred and twenty SD rats were used in this study (one hundred and four rats loading 0.39 N elastic force, another one hundred and four rats loading 1.18 N elastic force, while twelve rats for control). The extra-joint device was fixed on the right side by surgery. Half of the experimental group was killed at 3, 7, 14, 28 days. The devices were removed at the 28th day in the rest rats, and the rats were sacrificed at 3, 7, 14, 28 days after removing the device. The type II collagen expression levels of all the joints were measured using immunohistochemical techniques.

RESULTSThe positive expression of the type II collagen was mainly observed in the cytoplasm of chondrocyte, especially in maturative and hypertrophic layer. The expression intensity was different in different stages and different sides. Both of the two experimental groups showed the same tendency, while the changes in the light force group were more obviously than the heavy force group. In the right side (force-loading side), the type II collagen expression decreased at the early force-loading period. After the device was removed, the expressions increased immediately but then reach the lowest level. The expression almost recovered to normal level at the end of experiment. In the left side (none force-loading side), the expression remained increasing after force-loading and reached the peak at the 14th day.

CONCLUSIONThese results suggest that even in the adult individuals, the chondrocyte showed reaction to the mechanical force by altering type II collagen expression patterns and it may be the cause of the cartilage remolding after asymmetric inter-maxillary traction. A forward elastic force showed a depressant effect in matrix synthesis, and heavy force had stronger effect. But the rotation of condyle accelerated the matrix synthesis.

Animals ; Cartilage ; Chondrocytes ; Collagen Type II ; Mandibular Condyle ; Rats ; Rats, Sprague-Dawley ; Traction

Objective To investigate the relationship between lipoprotein-related phospholipase A2(Lp-PLA2),homocysteine (Hcy),beta-N-1-deoxy fructosyl component of hemoglobin(HbAlc),low density lipoprotein cholesterol(LDL-C)and cere-bral microbleeds in patients.Methods Patients with CMBs were consecutively recruited from the Department of Neurology, in Shaanxi Provincial People's Hospital by using the diagnostic criteria according to the diagnosis and treatment of cerebral cerebrovascular disease in China in 2014.In addition,volunteers were included as normal controls.The demographic charac-teristics and the history of patients were collected.The level of Lp-PLA2,Hcy,HbA1c and LDL-C in each group was ana-lyzed.Results 62 patients with CMBs were included in this study,including 48 males and 14 females.30 patients were in-cluded into the normal control group,including 20 males and 10 females.The levels of Lp-PLA2,Hcy and HbA1c in the CMBs group were significantly higher than those in the control group(t=2.67,2.97,3.24,P<0.05).The level of HbA1c levels were correlated with the number of CMBs(r=0.287,P=0.024).The level of HbA1c was correlated with the num-ber of CMBs in deep white matter(r=0.304,P=0.016),while it was not correlated with the number of CMBs in the cortex (P>0.05).Conclusion The levels of Lp-PLA2,Hcy and HbA1c in CMBs were higher than those in normal control group. HbA1c levels were associated with the number of CMBs,especially in deep white matter.

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.
Child, Preschool ; Diagnosis, Differential ; Humans ; Leigh Disease ; diagnosis ; genetics ; therapy ; Male ; Mutation ; Pyruvate Dehydrogenase (Lipoamide) ; genetics

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.
Adolescent ; DNA, Mitochondrial ; genetics ; Electron Transport Complex I ; deficiency ; Humans ; Leigh Disease ; genetics ; Male ; Mutation

OBJECTIVETo analyze and review the characteristics of leukoencephalopathy with vanishing white matter (VWM).

METHODSThe clinical features including clinical manifestations, neurologic signs, cranial MRI and laboratory tests in 9 patients with the diagnosis of VWM were analyzed and the characteristics of the disease were reviewed.

RESULTS

CLINICAL MANIFESTATIONS8 cases had symptoms involving central nervous system, 1 case only showed abnormal cranial MRI findings. The onset of the disease occurred between 6 months to 3 years of age. Family history was positive in 5 cases. Almost all cases had normal psychomotor development before the onset of the disease. The initial symptom was usually movement disorder with predominant involvement of lower limbs. The onset or deterioration of the disease was followed by respiratory tract infection in 6 cases and minor head trauma preexisted in 3 cases. The course of the disease was progressive in 7 cases and there was episodic deterioration in 4 cases. Mental abilities were relatively better preserved. Head circumference was normal in 7 cases. Positive upper motor unit signs were found in 8 cases and ataxia in 4 cases. Bilateral optic nerve atrophy was found in 3 cases. Cranial MRI indicated diffuse and symmetrical involvement of deep white matter which showed long T(1) and T(2) signal. Subcortical white matter was also involved with predominance in frontal and parietal lobes. Flair image showed symmetrical high signal intensity in cerebral white matter with low signal intensity similar to that of CSF in partial area or low signal in most area of white matter with only meshwork of higher signal preserved. The results of all the laboratory tests including the enzyme and biochemical test specific for some well-known leukoencephalopathy were normal.

CONCLUSIONSThe clinical features of VWM include: 1. Initial symptom is usually movement disorder; 2. Movement disorder is more prominent compared to mental retardation; 3. Cranial MRI shows symmetrical abnormal T(1) and T(2) signal in deep white matter with signs of vanishing white matter. Exclusion of other hereditary and acquired leukoencephalopathy is necessary for diagnosis. Final diagnosis should be made on the basis of genetic evidence.

Adolescent ; Age of Onset ; Brain ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukoencephalopathies ; pathology ; Magnetic Resonance Imaging ; Male ; Movement Disorders ; physiopathology

Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.
Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Ethers ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Molecular Docking Simulation ; Molecular Structure ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; metabolism ; Pyrimidines ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the presence of Cosmc gene mutation in children with Henoch-Schönlein purpura (HSP) and the association between Cosmc gene mutation and the susceptibility to HSP.

MESULTSEighty-four children who were diagnosed with HSP between March 2014 and December 2015 were selected as the HSP group. Fifty-eight healthy volunteers matched for age and sex were enrolled as the control group. Fasting venous blood (5 mL) from the two groups was collected in EDTA anticoagulated tubes, followed by the isolation of peripheral blood mononuclear cells (PBMCs) through density gradient centrifugation. Genomic DNA was extracted from PBMCs according to the manufacturer's protocol, and the whole exon region of Cosmc gene was amplified by touch-down polymerase chain reaction (touch-down PCR). The PCR products were identified by 1% agarose gel and sequenced in order to further examine the association between Cosmc gene mutation and the susceptibility to HSP.

RESULTSSequencing results showed two mutations (c.393T>A and c.72A>G) of Cosmc gene in children with HSP. There were no significant differences in the genotype and allele frequencies at the two loci between the HSP and control groups, and this distribution was not associated with sex.

CONCLUSIONSThe mutations c.393T>A and c.72A>G in the exon region of Cosmc gene in children with HSP are not associated with the onset of HSP.

Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Molecular Chaperones ; genetics ; Mutation ; Purpura, Schoenlein-Henoch ; etiology ; genetics