Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical research. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel approach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (sodium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs. The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associated markers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcinogenicity and the use of exogenous reprogramming factors.

Objective To study the effect of topiramate(TPM) on serum level of leptin and the expression of neuropeptide Y(NPY) in arcuate nucleus and their relationship with weight changes in pentetruzole-induced epileptic rats,and to explore the mechanism that TPM could reduce the weight.Methods One hundred and fifteen Wistar rats were randomly divided into 4 groups:blank control group,TPM contrast group,pentylenetetrazol(PTZ) model group,and TPM group.Weight changes were measured every 3 days.Serum leptin level was detected with rodioimmunity method and hypothalamic arcuate nucleus NPY expression was measured by immunohistochemical ABC technique at the 2~(nd),4~(th),6~(th) weekend,respectively.Results In TPM control group and TPM group weight loss appeared in the 4~(th) week compared with other groups at the 3~(rd) weekend and fell to the lowest at 4~(th) weekend(P

OBJECTIVEParkinson's disease (PD), a neurodegenerative disorder, has been reported to be associated with brain neuroinflammation in its pathogenesis. Herein, changes in peripheral immune system were determined to better understand PD pathogenesis and provide possible target for treatment of PD through improvement of immune disorder.

METHODS1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into mice to prepare PD model. Expression levels of pro-inflammatory and anti-inflammatory cytokines and transcription factors of CD4+ T lymphocyte subsets in spleen and mesenteric lymph nodes and concentrations of the cytokines in serum were examined on day 7 after MPTP injection. Percentages of CD4+ T lymphocyte subsets were measured by flow cytometry.

RESULTSMPTP induced PD-like changes such as motor and behavioral deficits and nigrostriatal impairment. Expression levels of the pro-inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-17 and IL-22, in spleen and mesenteric lymph nodes were upregulated and their concentrations in serum were elevated in PD progression. But, the concentrations of the anti-inflammatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-β were not altered in the two lymphoid tissues or serum of PD mice. In addition, expression of T-box in T cells (T-bet), the specific transcription factor of helper T (Th) 1 cells, was downregulated, but expression of transcription factor forkhead box p3 (Foxp3), the transcription factor of regulatory T (Treg) cells, was upregulated. In support of the results, the numbers of IFN-γ-producing CD4+ cells (Th1 cells) were reduced but CD4+CD25+ cells (Treg cells) were elevated in both the lymphoid tissues of PD mice.

CONCLUSIONPD has a dysfunction of peripheral immune system. It manifests enhancement of proinflammatory response and CD4+ T cell differentiation bias towards Treg cells away from Th1 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; CD4-Positive T-Lymphocytes ; pathology ; Cell Differentiation ; Cytokines ; blood ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukins ; blood ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Parkinson Disease ; immunology ; physiopathology ; Spleen ; cytology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells ; Transforming Growth Factor beta ; blood

Castleman Disease ; complications ; metabolism ; pathology ; surgery ; Dendritic Cell Sarcoma, Follicular ; complications ; metabolism ; pathology ; surgery ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Receptors, Complement 3b ; metabolism ; Thoracic Diseases ; complications ; metabolism ; pathology ; surgery ; Thoracic Wall ; Vimentin ; metabolism

Total 967 patients with diabetes mellitus treated in Morindawa People's Hospital from June 2012 to June 2014 were included in the study,among them 425 (44.0％) were of Daur nationality and 542 (56.0％) were of Han nationality.The clinical data and laboratory tests were analyzed and compared between two groups.Compared with Han nationality,Daur patients presented a younger average age[(55 ± 1 1) y vs.(58 ± 1 0) y,P=0.000],an earlier age of onset[(50±10)y vs.(53 ± 1 1) y,P=0.000],a higher percentage of males (54.8％ vs.46.9％,P =0.008),a higher percentage of rural residents (42.1％ vs.36.2％,P =0.034),a lower level of fasting blood-glucose (FBG) [(9.25 ± 3.37) mmol/L vs.(10.28 ±4.33) mmol/L,P =0.000],higher levels of HbA1c [(7.61 ± 1.71)％ vs.(7.29 ± 1.63)％,P=0.008],triglyceride (TG) [(2.91 ±2.06) mmol/L vs.(2.36 ±2.13) mmol/L,P =0.008],low density lipoprotein cholesterol (LDL-C) [(3.22 ± 1.06) mmol/L vs.(3.01 ±0.92)mmol/L,P=0.020],systolic blood pressure (SBP) [(139.48 ± 21.58) mmHg (1 mmHg =0.133 kPa) vs.(136.37 ± 23.44) mmHg,P =0.002],diastolic blood pressure (DBP) [(87.23 ± 12.59) mmHg vs.(85.32 ± 12.52) mmHg,P =0.019],blood uric acid [(324.97 ± 106.45) μmol/L vs.(285.32 ± 98.69) μmol/L,P =0.000] and the ratio of urine microalbumin to urine creatinine [(2.29 ±5.57) mg/g vs.(0.12 ±0.98) mg/g,P =0.000].The results show that Daur diabetic patients are.younger in age,with more severe disorders in HbA1 c,blood pressure,blood uric acid and lipids levels,which increase the probability of renal damage or cardiovascular diseases in these patients.

OBJECTIVE: To assess the long-term clinical efficacy of endoscopic surgery of primary sinonasal malignant neoplasms and find out the potential postoperative prognostic factors. METHOD: Forty-three clinical cases of primary sinonasal malignant neoplasms treated under endoscopy were analyzed retrospectively. RESULT: Fifteen patients died. The 1-year, 2-year, 3-year and 5-year survival rates were 83. 7% (36/43), 74. 4% (32/43), 69. 8% (30/43) and 65. 1% (28/43), respectively. Kaplan-Meier single-variable analysis showed that gender, T grade, TNM stage and pathological types of olfactory neuroblastoma were statistically significant prognostic factors (P< 0. 05). COX Pro-Portional hazard models showed that TNM stage was an independent prognostic factors. CONCLUSION Endoscopic surgery for primary sinonasal malignant neoplasms is a safe and effective minimally invasive surgical treatment, and it is an important supplement to the traditional surgery. Gender, T grade, TNM stage and pathological types of olfactory neuroblastoma might be significant prognostic factors.
Endoscopy ; Esthesioneuroblastoma, Olfactory ; surgery ; Humans ; Nasal Cavity ; pathology ; surgery ; Nose Neoplasms ; surgery ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Objective To compare the differences of five diagnostic criteria used for metabolic syndrome (MS),issued by International Diabetes Federation (IDF),the National Cholesterol Education Program (ATPIII),America-Heart-Associatien (AHA),Chinese Medical Association Diabetes Branch (CDS) and The Taiwan Health Bureau (TAIWAN),during a physical check-up program among population aged 35-74 years,in Taiwan.Methods A total number of 28 408 people who had received physical checkup program first time at the MJ centers,were recruited from 2005 to 2007.The prevalence of MS and the degree of agreement were both calculated according to the five definitions and the results of MS components.Distributions and risk factor aggregation of the results were also analyzed.Results According to the five definitions (1)The range of age-adjusted prevalence of MS appeared to be 10.6%(CDS)23.6%(AHA),and were 13.4%(CDS)-27.6%(AliA)and 8.0%(CDS)-20.5%(IDF) for men and women respectively.(2) The range of five MS components were 22.5%(low-HDL-C)-39.7%(high FPG),with 22.3%of the total subjects presented at least 3 risk factors.In addition,0%(AHA),6.7%(TAIWAN),6.9%(ATP III),8.9%(IDF) and 14.9%(CDS) of the subjects diagnosed as MS-free,by the five criterions,also appeared of having≥3 risk factors.(3) Among all the MS subjects,the proportions of clinical symptom complex,having 5,4 and 3 MS components were 8.0%,29.5%and 62.5%respectively.The most common clinical symptoms complex of MS were obesity,hypertension and high FPG.(4) The MS diagnostic criteria of ATPIII,AHA and TAIWAN were in good accordance with Kappa index,showing 0.81-0.98 for the three criteria.CDS and IDF were in relatively weak agreementwhen comparing with other definitions with Kappa index showed as 0.35 and 0.62.Conclusion Our findings revealed big differences in the prevalence and aggregation of risk components on MS,when using the five definitions.We suggested that prospective cohort studies be planned to investigate the impact on cardiovascular disease morbidity and mortality so as to verify whies criterion might be suitable to the population in Taiwan,considering the possible bias.

Adenoids ; diagnostic imaging ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Hypertrophy ; Magnetic Resonance Imaging ; Male ; Radiographic Image Enhancement ; methods ; Tomography, Spiral Computed ; methods

Disease ; etiology ; Epidemiology ; Humans

OBJECTIVETo investigate the developmental profiles on surface expression and co-localization of NMDA receptor clusters and AMPA receptor clusters on dendrite in cultured hippocampal neurons of rats.

METHODSGreen fluorescent protein tagged GluR2 subunit (GFP-GluR2) and FLAG tagged NR2B subunit (FLAG-NR2B) were transfected into cultured hippocampal neurons at 5 days in vitro (DIV5). FLAG-NR2B containing NMDA receptor clusters and GFP-GluR2 containing AMPA receptor clusters expressed on membrane surface were then labeled in living neurons using anti FLAG mAb/Cy3-conjugated anti-mouse antibody and anti-GFP pAb/Alex488-conjugated anti-rabbit antibody.

RESULTThe numbers of receptor cluster per 100 microm dendrite in the neurons at DIV7 and DIV19 were 39.7+/-5.0 and 64.7+/-6.1 (P<0.01) for NR2B-NMDAR, 59.1+/-3.3 and 99.7+/-6.4 (P<0.01) for GluR2-AMPAR, and 29.9+/-4.5 and 37.5+/-2.5(P<0.05) for the co-localized, respectively. At DIV7 and DIV19, 75.4% and 57.9% NR2B-NMDAR clusters were co-localized with GluR2-AMPAR; and 50.6% and 37.6% GluR2-AMPAR clusters were co-localized with NR2B-NMDAR, respectively.

CONCLUSIONThe density of NR2B-NMDAR containing and GluR2-AMPAR containing receptor clusters increases during development of hippocampal neurons in culture. Although the co-localized clusters are increased as well in an unit length of dendrite, the extent to which the two receptor clusters are co-localized decreases. These data imply a possible change in the partnership of AMPA receptor subtype and NMDA receptor subtype at newly formed synapses during development.

Animals ; Cells, Cultured ; Dendrites ; chemistry ; Hippocampus ; chemistry ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; analysis ; Receptors, N-Methyl-D-Aspartate ; analysis