Objective To assess the feasibility of using PET molecular imaging to evaluate the therapeutic effects of traditional Chinese medicine FuZhiSan (FZS) on the model of aging Alzheimer's disease (AD) rats. Methods Twenty aged AD rats (Sparague-Dawley rats,male) were randomly divided into FZS treated group (n = 10) and control group (n = 10). Another 10 healthy adult rats were as blank controls. Morris water maze record system was used for cognitive function assessment. Before and after FZS treatment 18 F-fluorodeoxyglucose (FDG) and 11 C-2- [4'-(methylamino) phenyl] benzothiazol-6-ol ( PIB )PET imaging was undertaken. After post-treatment imaging procedures the brain tissues of all animals were taken for histochemical study,such as staining with HE,congo red,amyloid β (Aβ) immunofluorescence,5-bromo-2-deoxyuridine (BrdU) immunofluorescence and NeuN immunofluorescence. Paired t-test was performed with SPSS 13.0 software for the data analysis. Results The cognitive dysfunction of aging AD rats was improved after FZS treatment. The escape latency in FZS treated group was significantly shorter than that of control group ((32.5 ±10.8) s vs (102.6±8.8) s,t =15.7987,P=0. 0001). Diffuse neuronal loss and Aβ deposition were detected in the hippocampus and cortex in the aged AD rats. The imaging data showed that brain glucose metabolism was amended in FZS treated group while the abatement of amyloid deposition was not significant. Immunofluorescence results indicated that the neuronal proliferation was more remarkable in FZS treated group. Conclusions It may be feasible to use PET imaging as a method to evaluate the therapeutic effect in AD rats. FZS may ameliorate memory dysfunction of aged AD rats. Its mechanism may be partly contributed to the enhancement of the neuronal proliferation and survival.

Objective To observe the expressions of oxidized low density lipoprotein ( OxLDL ) receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index(STI)ofdiabetesgroupwashigherthanthatincontrolgroup(5.54±1.5vs0.65±0.15,P<0.05). OxLDL stimulated CD36 expression in NRK-52E cells in a dose-and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes.

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.

OBJECTIVE: To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). METHODS: Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. RESULTS: A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic". CONCLUSIONS Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.
Charcot-Marie-Tooth Disease ; Child ; Child, Preschool ; Female ; Genetic Testing ; Genotype ; Humans ; Male ; Mutation

OBJECTIVETo study the antioxidant constituents from the root of Rubus crataegifolius.

METHODThe constituents isolation and purification from the root of R. crataegifolius was carried by reported column chromatography including silica gel, toyopearl, and their structures were elucidated on the basis of spectral compounds. DPPH method was used to evaluate the free radical scavenging activity of the isolated compounds.

RESULTNine compounds were isolated from the root of R. crataegifolius, and their structures were identified as follow: euscaphic acid (1), kaempferol-3-O-beta-D-galactopyranoside (2), tormentic acid (3), 2alpha, 19alpha, 24-trihydroxyurs-12-ene-3-oxo-28-acid (4) , 2alpha-hydroxy-oleanolic acid (5), ursolic acid (6), daucosterol (7), beta-sitosterol (8) and polydatin (9). By experiment of antioxidant activity, the result showed compounds 2 and 9 revealed DPPH free radical scavenging rates were 95.60% and 75.23% at the concentration of 50 mg x L(-1).

CONCLUSIONCompounds 1-8 were isolated from this plant for the first time, and compounds 2 and 9 showed the significant antioxidant activity.

Antioxidants ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Rosaceae ; chemistry

OBJECTIVETo investigate the expression of HPA and HIF-1alpha in human esophageal squamous cell carcinoma and their relationship with cancer development, invasion and metastasis.

METHODSThe expression of HPA mRNA and HIF-1alpha protein in 23 mucosa specimens of incisal margin, 26 para-tumorous dysplastic tissues and 70 esophageal squamous cell carcinoma specimens were detected by in situ hybridization assay and immunohistochemical staining, respectively.

RESULTSThe positive expression of HPA mRNA and HIF-1alpha protein were significantly increased as the epithelial cells progressed into carcinoma (P < 0.05). The expression of HPA mRNA and HIF-1alpha protein in the esophageal squamous cell carcinoma were significantly correlated with the invasion depth, lymph node metastasis and clinical staging (P < 0.05), while it was not correlated with the differentiation of tumors (P > 0.05). There was a close correlation between the expression of HPA mRNA and HIF-1alpha protein in the carcinoma tissues (P < 0.01).

CONCLUSIONThe high expression of HPA mRNA and HIF-1alpha protein is correlated with carcinogenesis, progression, invasion and metastasis of esophageal squamous cell carcinoma. There may be a positive cooperation between two of them in the carcinogenesis and development of esophageal carcinoma. The determination of HPA mRNA and HIF-1 alpha will be useful in predicting tumor biological behavior.

Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Esophageal Neoplasms ; metabolism ; pathology ; Esophagus ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Glucuronidase ; genetics ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Immunohistochemistry ; In Situ Hybridization ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucous Membrane ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; metabolism

Objective To analyze the relationship between strain subtypes and transmission of HIV infection on marriage-based immigrant women,their spouses and children in rural area of Zhejiang province.Methods Marriage-based immigrant women with HIV infection,their HIV infected spouses and children in rural area in Zhejiang province,were selected as study objects.Analysis on genetic sequence and epidemiologic information was carried out.Subgenomic gag was amplified by nest-PCR analysis on the whole blood samples.Genetic subtype characterization and the source of HIV strains were analyzed.Relationships on sequences were also examined by phylogenetic tree analysis.Results Genetic sequences of 72 samples from HIV infected marriage-based immigrant women were obtained.The genetic subtypes comprised 21 CRF01_AE (29.2％),12CRF07 BC (16.7％),31 CRF08 BC (43.1％),6 B (8.3％),2 C (2.8％).HIV strains from 45 cases (62.5％) were similar to the prevalent HIV strains in the province where former census of marriagebased immigrant women were registered.In total,there were 26 (70.3％) cases from Yunnan province.84.7％ of the infected women had heterosexual behaviors before settling down in Zhejiang province.Genetic sequences of 17 pairs showed the same subtype between the couples and data from phylogenetic tree analysis supported the assumption of transmission linkage in the family.Conclusion The HIV subtype strains detected in those HIV infected marriage-based immigrant women in the rural area of Zhejiang province characterized with diversity,showing CRF08_BC and CRF01_AE were the main HIV strain subtypes.HIV infection originated mainly fiom Yunnan province and nearby regions.Heterosexual behaviors of the marriage-based immigrant women in the original region where they had their residence registration,seemed to be the primary high risk factors for these women.Surveillance and intervention programs on these marriage-based immigrant women and their family members should be improved.

OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia cambogia (Clusiaceae) are widely developed as health products for anti-obese purpose. 14-deoxygarcinol (DOG) is a polyisoprenylated benzophenone from the fruits of G. cambogia, which showed potent anti-inflammatory effect in our previous study. The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance. METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages. The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting, immunofluorescence staining and co-immu?noprecipitation. The pro-inflammatory cytokines levels were determined by ELISA kits. RESULTS DOG increased the expression of Sirtuin 2 (SIRT2) deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflamma?some activation and IL-1βsecretion in THP-1 macrophages. Moreover, DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes. CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition, which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.

OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania. METHODS: Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA. RESULTS: The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05). CONCLUSION Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.
Aggression/drug effects* ; Antipsychotic Agents/therapeutic use* ; Biomarkers/blood* ; Bipolar Disorder/drug therapy* ; Case-Control Studies ; Diagnostic and Statistical Manual of Mental Disorders ; Double-Blind Method ; Humans ; Interleukin-17/metabolism* ; Lithium Compounds/therapeutic use* ; Quetiapine Fumarate/therapeutic use* ; Treatment Outcome

OBJECTIVETo evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA).

METHODSThe clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)×10(6)/kg in allo-BMT and 2.95 (1.27 - 5.98)×10(6)/kg in allo-PBSCT, respectively.

RESULTSHematopoietic reconstitution was observed in all 41 patients (100%). The median time of neutrophils (ANC) reached to 0.5×10(9)/L and platelets (PLT) reached to 20×10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79) months. 36 patients survived. 5-year estimated overall survival (OS), disease free survival (DFS), and transplant-related mortality (TRM) was (81.1 ± 9.0)%, (68.4 ± 11.0)%, and (18.9 ± 9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34(+) cells no more than 2.5×10(6)/kg, the number of red blood cell (RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34(+) cells no more than 2.5× 10(6)/kg (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation (P = 0.038).

CONCLUSIONMSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34(+) cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.

Adolescent ; Adult ; Anemia, Aplastic ; therapy ; Child ; Child, Preschool ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Retrospective Studies ; Siblings ; Tissue Donors ; Treatment Outcome ; Young Adult