The aims of this paper were to define (1) criteria of cerebral palsy; (2) classification of cerebral palsy; (3) etiology, neuroimaging, and epidemiology of cerebral palsy; (4) different kinds of treatments of cerebral palsy. Data were drawn from an international survey of PUBMED (1994-2014) and CNKI (1994-2014). An expert panel used a consensus building technique. The10-point Jadad scale was used to assess the quality of the trials based on the following items, including allocation sequence generation, randomization concealment, methods of blinding, and descriptions of withdrawals and dropouts. Our clinical experience was also summarized. Below is a summary. (1) Further work is warranted to reach agreement for the classification of cerebral palsy. (2) A worldwide prevalence of 1.5-4.0 per 1 000 live births, with an average lifetime cost of 1 million dollars per person in the United States, while it is 1.8-6.0 per 1000 live births in China. (3) Comparison of clinical efficacy of different treatments. In this review, the current advances in different kind of treatments of brain injury are discussed with specific relevance to cerebral palsy.
Cerebral Palsy ; classification ; diagnosis ; therapy ; China ; Humans ; Prevalence ; United States

Objective To investigate the effect of insulin on D_5 dopamine receptor expression and function in renal proximal tubule (RPT).Methods Immortalized RPT cells and D_5 receptor transfected HEK293 (HEK-D_5) cells were used in the study to investigate the effect of insulin on D_5 receptor expression and function,and those effects were compared in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The function of D_5 receptor was determined by measurement of the Na~+-K~+-ATPase activity in HEK-D_5 cells. Results Insulin increased D_5 receptor protein expression in a concentration and time-dependent manner in WKY RPT cells,but not in SHR.The basal level of D_5 receptor expression was higher in WKY cells than that in SHR cells. Stimulation with fenoldopam(D_1-like dopamine receptor agonist) inhibited the Na~+-K~+-ATPase activity;pretreat- ment with insulin increased the inhibitory effect of fenoldopam on Na~+-K~+-ATPase activity in HEK-D_5 cells. Conclusion The abnormal regulation of insulin on D_5 receptor expression and function might be involved in the path- ogenesis of essential hypertension.

Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.
Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Drug Discovery ; methods ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; Linagliptin ; chemical synthesis ; chemistry ; Molecular Structure ; Piperidines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Uracil ; analogs & derivatives ; chemical synthesis ; chemistry

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

Objective To investigate the changes of the cervical spinal cord in patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing neuromyelitis optica (RNMO) using diffusion tensor imaging (DTI) and to analyze its correlations with clinical disability scores.Methods Thirty patients with MS (MS group),28 patients with NMO (NMO group) and 20 healthy volunteers were imaged using DTI on a 3.0 Tesla scanner.DTI indices of cervical spinal cord from all participants were measured,including mean diffusivity (MD) and fractional anisotropy (FA),and the correlations between the DTI metrics and the expanded disability status scale (EDSS) scores were assessed.One-way ANOVA,Dunnett-t test and Spearman correlation analysis were used for statistics.Results (1) The values of MD among three groups were different at C3 level for left lateral and dorsal columns,C4 level for the central gray substance and dorsal columns,and C5-C6 level for all structures.There were significant differences among them (F =4.006-36.814,P ＜ 0.05).The values of FA were significantly different at all levels (F =5.561-98.128,P ＜0.05).(2) Compared with the control group,the values of MD were increased and FA were decreased for both MS and NMO groups,there were significant differences among them (t =-0.320-3.138,P ＜0.05).In MS and NMO groups,there were no significant differences of MD (t =-1.183-0.069,P ＞0.05),while the FA at C4-C6 levels (including the central gray substance,dorsal columns,right lateral columns and left lateral columns) for NMO group were 0.57 ± 0.09,0.56 ± 0.11,0.54 ±0.10,0.57±0.09,0.55 ±0.11,0.52 ±0.13,0.55 ±0.11,0.54 ±0.13,0.54±0.10,0.54±0.11,0.53 ±0.13,0.52 ±0.11 ;and for MS group were 0.67 ±0.10,0.68 ±0.10,0.68 ±0.10,0.70 ±0.12,0.68 ±0.11,0.69±0.10,0.68 ±0.11,0.69 ±0.12,0.67 ±0.14,0.68 ±0.15,0.69 ±0.14,0.69 ±0.16,and there were significant differences between two groups (t =-0.011-0.169,P ＜ 0.05).(3)Univariate correlations between DTI measures and the average EDSS scores were assessed.The MD at all levels showed significant positive correlations with disability scores (r =0.324-0.541,P ＜ 0.05),and FA significant negative correlated with disability scores (r =-0.632--0.294,P ＜ 0.05),except C4 level for lateral columns and C2 level.Conclusions DTI metrics are sensitive to cervical spinal cord damage in demyelinating diseases,providing an important way of distinguishing MS from NMO,and can be potentially useful quantitative biomarkers for monitoring the evolution of demyelinating diseases.

ObjectiveTo explore the values of 3D enhanced T2-star weighted angiography (ESWAN) in detecting iron deposition of the brain in patients with multiple sclerosis ( MS).Methods Conventional MRI and 3D ESWAN were performed in 22 patients with released-remitting MS(RR-MS) and in 22 age- and gender-matched normal controls.Both the magnitude images and phase images were available after post processing of the original ESWAN data post processing.The expanded disability status scale (EDSS) scores of the patients were from 0 to 8.5,and the course of disease were between 0.5 year and 15 years.The manifestation of MS lesions was evaluated on conventional MR images and ESWAN images by two experienced radiologists with blind methods.The phase values were measured for MS lesions between the semioval center and periventricular white matter and the corresponding regions in the normal control group were measured as well The Wilcoxon rank test was used to compare the differences of phase values between MS patients and normal controls,and the Spearman rank correlation analysis were used to analyze the correlations among the phase values of MS lesions,EDSS scores and course of disease of MS patients.Results( 1 ) MS lesions were observed on magnitude images and phase images,respectively and together.Two hundred and thirteen(32.8％ )lesions were detected on both the magnitude images and phase images,164 (25.2％)lesions were detected on the magnitude images only,and 273 (42.0％) lesions were detected on the phase images only.A total of 650 lesions were observed on the ESWAN,which showed more 42 lesions than conventional images(608).Among 486(273 + 213 )lesions observed on the phase images,205 (31.5％) lesions were homogeneously hypointense,45 (6.9％ ) lesions showed hypointense ring,and 236 (36.4％ ) lesions were inhomogeneously hypointense.(2) “ Penetrating veins” were showed in 424 (65.2％ ) periventricular lesions.The “penetrating veins” showed dilated and prolonged in 198 (30.5％ ) acute lesions,thin and short in 208 (32.9％ ) chronic lesions.However,the “penetrating veins” of 12 ( 1.8％ ) chronic lesions in 5 stable MS patients were expanded and prolonged slightly.( 3 ) The average phase value of the lesions ( - 0.05 ± 0.08) in patients with RR-MS was significantly lower than that of corresponding to regions (0.06 ± 0.05 ) in the normal control group( Z = 22.30,P ＜ 0.01 ).(4) The phase values of MS lesions were significantly correlated to the EDSS and course of disease of patients with RR-MS (r = -0.98,0.99 respectively,P ＜ 0.01 ).ConclusionESWAN can be helpful in the evaluation and quantification of abnormal iron deposition in MS lesions,which provides important values for the pathogenesis and pathological study for MS patients.

OBJECTIVE Study the kidney toxic effects caused by burning coal endemic arsenism in rats,application bench mark dose (BMD) method to investigate the bench mark dose of urinary arsenic (UAs)and the changes in bio markers of renal function.METHODS Wistar rats were fed for 90 d with arsenic 0,25,50,100 mg·kg -1 conta minated feed.Urinary arsenic,kidney arsenic and renal function indicators were determined,and routine pathological and fibrosis of kidney were exa mined.UAs as the exposure bio marker,Uβ2-MG,UNAG and UALB for the effect bio markers,application bench mark dose method to calculate the BMD and BMDL of UAs for each effect bio markers.RESULTS UAs,KAs, Uβ2-MG,UNAG,UALB levels of rats in arsenic 100 mg·kg -1 group were increased than normal group (P <0.05);In light microscope,the results of HE staining of rat kidney in all arsenic dose groups showed infla mmatory cell infiltration,renal tubular epithelial cell swelling,renal interstitial capillary dila-tion,congestion and other varying degrees pathological changes,and the results of masson staining showed varying degrees of tubulointerstitial fibrosis;UAs as the exposure bio marker,Uβ2-MG,UNAG, UALB for the effects of mark,the BMD and BMDL of UAs for Uβ2-MG,UNAG,UALB were calculated, the BMD values were 998.9,1213.5,1386.9 μg·g -1 Cr,the BMDL values were 660.5,803.6 and 909. 4 μg·g -1 Cr,respectively.CONCLUSION Burning coal arsenic pollution can cause kidney da mage in rats,mini mal change nephropathy may be the pri mary pathological in the coal arsenic conta mination of kidney da mage.The BMD and BMDL of UAs were 998.9,660.5 μg·g -1 Cr,the early changes of renal function of burning coal arsenism in rats;it is reco mmended to use the more sensitive bio markers Uβ2-MG to calculate the biological exposure li mits on renal injury caused by arsenic.

Objective To observe the expressions of bone morphogenetic protein-2(BMP-2)and bone morphogenetie protein-7(BMP-7)in the synovial tissue of fluorosis rats and its correlation with pathogenic mechanism of fluorosis arthritis.Methods Thirty-two SD rats were randomly divided into 4 groups:the control group,low,moderate and high-dose fluoride group.The control group ate commou fodder.The low,moderate and high dose fluoride group were fed with fodder composed of 25%.35%and 68%of corn(containing fluorine of 148.00 mg/kg)in chronic endemic fluorosis region in Guizhou Province.After 140 days,the expressions of BMP-2 and BMP-7 protein were determined by immunohistochemistry and assayed the absorbanee by computer image-pattern analysis system.Light microscope was used to observe the synovial tissue by Hematoxin Eosin,and calculated the pathological integral of synovium according to pathological grade standard.Results The expressions of BMP-2 (32.50±2.73)and BMP-7(38.90±2.56)in the control group was spare.Compared with the control group,the expressions of BMP-2(59.43±5.12,79.82±6.41,101.76±7.56)and BMP-7(55.10±4.82,78.42±5.61,98.46± 6.05)in the synovial tissue was up-regulated in each experimental groups(P＜0.05),especially in the moderate dose and the high-dose groups(P＜0.05).Compared with the control group(0.54±0.21).the pathological integral of synovium increased(P＜0.05)in each experimental groups(1.04±0.98,4.69±1.28,8.60±2.07).The expressions of BMP-2 and BMP-7 in the synovial tissue was found to be positively related with the pathological integral of synovium(r=0.98,0.99,P＜0.05).Conclusion The BMP-2 and BMP-7 play an important role in the development of fluorosis arthritis,probably by affecting osteogenesis.

ObjectiveTo investigate the variation of thalamus metabolism in patients with multiple sclerosis (MS) or neuronmyelitis optica (NMO) using 1H-MRS.Methods1H-MRS was performed to 32 MS patients (MS group),28 NMO patients (NMO group) and 35 healthy volunteers (normal control group).The ratios of metabolism in thalamus,including N-acetylaspartic acid/creatine (NAA/Cr),choline/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) were calculated and compared.ResultsThere was statistical difference of NAA/Cr in thalamus among the three groups (P＜0.05).NAA/Cr in thalamus of MS group was significantly lower than that of normal control group (t= -3.45,P＜0.05),while no statistical difference of Cho/Cr and mI/Cr was found (t=0.086,0.661,all P＞0.05).No statistical difference of NAA/Cr,Cho/Cr or ml/Cr was found between NMO group and normal control group (t=-0.792,1.408,1.735,all P＞0.05).Conclusion1H-MRS shows the decrease of thalamus NAA/Cr that suggesting axon damage in MS patients,but in NMO patients no same result is found.1 H-MRS can reflect the pathological changes of MS and NMO,and improve the differential diagnosis of the two diseases.

BACKGROUND:The researches about the effect of retinoic acid on the proliferation of adipose-derived stem cells are rare, and the researches on the testosterone are mainly on the inhibition of cellaging. OBJECTIVE: To study the effects of retinoic acid and testosterone or combination on the cellcycle of adipose derived stem cells. METHODS:Adipose derived stem cells were isolated from adult female Sprague Dawley rats with 2 months age and cultured in vitro til passage 3 adipose derived stem cells, and then the 3rd passage adipose-derived stem cells were performed with adipogenic induction, osteogenic induction and surface marker identification. The cells were divided into six groups:(1) Control group;(2) 10-5 mol/L retinoic acid group;(3) Retinoic acid group;(4) 10-5 mol/L retinoic acid+testosterone group;(5) 10-6 mol/L retinoic acid+testosterone group;(6) Testosterone group. The adipose-derived stem cells in the control group were cultured with Dulbecco’s modified Eagle’s medium+10%fetal bovine serum culture medium, and the adipose-derived stem cells in the other five groups were induced with corresponding dose of retinoic acid and testosterone on the basis of control group. After cultured for 36 hours, the flow cytometry was used to detect the changes of cellcycle. RESULTS AND CONCLUSION:Compared with the control group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group were increased significantly, and the cellproportions in phase S were decreased. Compared with control group, the cellproportion in phase G 1 of testosterone group was significantly reduced, and the cellproportion in phase S was increased. Compared with 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid+testosterone group and 10-6 mol/L retinoic acid+testosterone group were reduced significantly and the cellproportions in phase S were increased. Retinoic acid can inhibit the cellcycle of adipose-derived stem cells in phase G 1 , and delay the process of the cellcycle from phase G1 to phase S;while testosterone can promote the cellcycle of adipose-derived stem cells from phase G1 to phase S;the combination induction of retinoic acid and testosterone can accelerate the process of the cellcycle of adipose-derived stem cells from phase G 1 to phase S.