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.

ObjectiveTocomparethedifferencesoftwostocksofguineapigs,thealbinoguineapigsandpigment guinea pigs , in establishing dyslipidemic model , to evaluate their lipid-lowering action , and to compare their properties for development of hyperlipidemia .Methods Two stocks of the 5-week-old guinea pigs were randomly divided into two groups, normal group (NC) and model group (Model).For the NC group, 12 guinea pigs were fed with normal chew .For the model group , after fed with high-fat diet for four weeks , 24 male guinea pigs were randomly grouped and treated with vehicle (VC group) and pitavastatin (Pit group) calcium, respectively, by gavage as well as received high-fat diet.Before and after modeling and pitavastatin treatment , blood samples were collected and subjected to analysis of plasma TC , TG, HDL-C and LDL-C, respectively .Results In the normal group , the blood lipid levels of albino guinea pigs were more stable than that of the pigmented pigs with the increase of age .After fed with high-fat diet , the plasma lipid levels of TC , TG and LDL-C were significantly increased in the two strains of guinea pigs , while HDL-C showed a decrease to varying degrees .Interestingly , the lipid level in the albino guinea pigs was significantly higher than that of pigment guinea pigs . And also, after drug administration for four weeks , pitavastatin treatment significantly decreased the elevated lipid level of TC, TG and LDL-C in the albino guinea pigs compared with that in the pigment guinea pigs .Conclusions The albino guinea pigs and pigment guinea pigs demonstrate certain differences in establishing dyslipidemic model and evaluating lipid -lowering pharmacodynamics .However , compared with the pigment guinea pigs , the albino guinea pigs have obvious superiority because of easy establishment of hyperlipidemia model and are more sensitive to lipid -lowering drugs .

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry

Chromosomes, Human, Y ; DNA Fingerprinting ; Humans ; Male

Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.
Drugs, Chinese Herbal ; chemistry ; Humans ; Panax notoginseng ; chemistry ; Protein Interaction Maps ; drug effects ; Proteins ; chemistry ; Saponins ; chemistry

The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.
Autophagy ; Humans ; Medicine, Chinese Traditional ; Proteasome Endopeptidase Complex

OBJECTIVETo delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China.

METHODSClinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing.

RESULTSThe 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases.

CONCLUSIONSThe phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.

Alexander Disease ; diagnosis ; genetics ; pathology ; Brain ; pathology ; Child ; Child, Preschool ; China ; epidemiology ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; genetics ; Heredodegenerative Disorders, Nervous System ; diagnosis ; genetics ; pathology ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Mutation, Missense ; genetics ; Seizures ; epidemiology ; Severity of Illness Index

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

Objective To study the mechanism of overexpression of retinoic acid receptor alpha( RARα)in attenuating renal interstitial fibrosis(RIP)in rats. Methods Porty 6_week_old male SD rats were randomly divided into 4 groups:sham operation group,model group,negative control group and transfection group,with 10 rats in each group. Rats in model group were separated and double ligated with left ureter;rats in sham operation group were not li_gated with ureter;rats in transfection group and negative control group were transfected with adeno_associated virus and negative control virus carrying RARα gene on the basis of model group,respectively. All rats were sacrificed 2 weeks later. Left kidney tissues were taken for pathological examination and RIP index was calculated. The expression of colla_genⅣ(Col_Ⅳ)and fibronectin(PN)in renal tissue was detected by using immunohistochemistry. The expressions of RARα,prohibitin(DHB)and transforming growth factor_beta 1(TGP_β1)in renal tissue were detected by using real_time fluorescence quantitative polymerase chain reaction( RT _qDCR)and Western blot. Results (1)Com_pared with sham operation group,the RIP index was significantly increased in model group(22. 81 ± 2. 43 vs. 2. 34 ± 0. 55,q﹦24. 94,P〈0. 05);compared with model group,the RIP index was not of significant difference in negative control group(22. 81 ± 0. 43 vs. 22. 26 ± 3. 43,q﹦0. 67,P〉0. 05),however it significantly decreased in transfection group(14. 06 ± 2. 99 vs. 22. 81 ± 2. 43,q﹦10. 66,P〈0. 05).(2)Compared with sham operation group,the mRNA and protein expressions of RARα,DHB significantly decreased in model group,but TGP_β1 mRNA and protein,Col_Ⅳand PN protein expression significantly increased in model group( mRNA:0. 43 ± 0. 17 vs. 1. 00 ± 0. 00,0. 34 ± 0. 08 vs. 1. 00 ± 0. 00,2. 97 ± 0. 54 vs. 1. 00 ± 0. 00,all P〈0. 05;protein:0. 25 ± 0. 10 vs. 0. 51 ± 0. 06,0. 24 ± 0. 07 vs. 0. 58 ± 0. 04,0. 59 ± 0. 09 vs. 0. 33 ± 0. 06,16. 01 ± 0. 87 vs. 8. 79 ± 0. 39,14. 64 ± 0. 32 vs. 9. 36 ± 0. 59,all P〈0. 05);com_pared with model group,the mRNA and protein expressions of RARα,DHB,TGP_β1 and Col_Ⅳand PN protein ex_pression had no significant difference in negative control group(all P〉0. 05);compared with model group,the mRNA and protein expression of RARα,DHB mRNA and protein expression significantly increased,but the TGP_β1 mRNA and protein,Col_Ⅳ and PN protein expression significantly decreased in transfected group( mRNA:0. 86 ± 0. 07 vs. 0. 43 ± 0. 17,0. 89 ± 0. 11 vs. 0. 34 ± 0. 08,1. 65 ± 0. 28 vs. 2. 97 ± 0. 54,all P〈0. 05;protein:0. 40 ± 0. 07 vs. 0. 25 ± 0. 10,0. 45 ± 0. 10 vs. 0. 24 ± 0. 07,0. 43 ± 0. 08 vs. 0. 59 ± 0. 09,11. 57 ± 0. 33 vs. 16. 01 ± 0. 87,11. 67 ± 0. 53 vs. 14. 64 ± 0. 32,all P〈0. 05).(3)Correlation analysis revealed that RARα protein expression was negatively correlated with RIP index,Col_Ⅳ,PN,TGP_β1(r﹦ _0. 78,_0. 78,_0. 76,_0. 76,all P〈0. 05);DHB protein expression was negatively correlated with RIP index,Col_Ⅳ,PN,TGP _β1( r ﹦ _0. 87,_0. 87,_0. 88,_0. 75,all P 〈0. 05);RARα protein was positively correlated with DHB(r﹦0. 85,P〈0. 05). Conclusion Overexpression of RARα could attenuate RIP by enhancing DHB expression in rats subjected to unilateral ureteral obstruction.

OBJECTIVETo investigate the effect of inhaled nitric oxide (NO) on surfactant protein A (SP-A) and mannose binding ability (MBA) in neonatal rats with hyperoxia-induced lung injury.

METHODSSixty-four neonatal rats were randomly exposed to room air (Control group), >95% oxygen for 6 days (Hyperoxia group), 10 ppm NO for 24 hrs (NO group), and >95% oxygen for 6 days along with 10 ppm NO for 24 hrs (Hyperoxia + NO group). After 2 and 6 days of exposure, the lung pathologic changes, gene and protein expressions of SP-A and MBA were measured.

RESULTSThe rats from the Hyperoxia group presented with obvious lung injuries. The SP-A expressions of mRNA (0.81 +/- 0.04 vs 1.53 +/- 0.25) and protein (59.45 +/- 18.37 vs 89.77 +/- 16.41) in the Hyperoxia group decreased significantly 2 days after exposure but increased significantly 6 days after exposure (SP-A mRNA 0.81 +/- 0.02 vs 0.63 +/- 0.03; SP-A protein 93.57 +/- 13.71 vs 47.73 +/- 21.69) compared with those of the Control group (P < 0.05). NO treatment alleviated the hyperoxia-induced pathologic injuries 2 days after exposure. The SP-A mRNA expression (0.55 +/- 0.91) in the Hyperoxia + NO group was significantly reduced as compared to both the Control and Hyperoxia groups (P < 0.05), and the SP-A protein expression (55.12 +/- 17.53) in the Hyperoxia + NO group was noticeably lower than that of the Control group (P < 0.01) 2 days after exposure. The SP-A protein expression in the Hyperoxia + NO group (67.33 +/- 18.59) was significantly lower than that of the Hyperoxia group 6 days after exposure (P < 0.05). Two days after exposure, the NO group had significantly higher MBA than the Control group (0.821 +/- 0.133 vs 0.58 +/- 0.158); the Hyperoxia + NO group had significantly higher MBA than the Hyperoxia group (0.43 +/- 0.175 vs 0.738 +/- 0.141) (P < 0.05).

CONCLUSIONSInhaled low dose NO may decrease SP-A protein expression and increase MBA of the lung tissue. This lessens the pathologic lung injury in neonatal rats with hyperoxia.

Administration, Inhalation ; Animals ; Animals, Newborn ; Hyperoxia ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Mannose ; metabolism ; Nitric Oxide ; administration & dosage ; Pulmonary Surfactant-Associated Protein A ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley