Objective Study the effects of early overfeeding in the adult offspring of mother with severely hyperglycaemia in pregnancy to islet development and insulin resistance. Methods Thirty healthy female Wistar rats were mated with 10 male Wistar rats and the morning on which sperm were found in three different visual fields of the vaginal smear was designated pregnancy day 1. The pregnant rats were intraperitoneally administered with Streptozotocin (STZ, 50 mg/L) on 5th day of pregnancy, and blood glucose exceeded 20 mmol/L to induce severely gestational diabetes mellitus (SDM) model. The pregnant Wistar rats were assigned to two experimental groups: SDM (n = 16) and control (n = 8). Litter size reduction in the lactation period induced early postnatal overfeeding model. Offspring were divided into three groups according to the level of blood glucose in pregnancy and feeding patterns in lactation: ( 1 ) control group (CG):euglycemia in pregnancy, eight pups in lactation;(2) severely gestational diabetes mellitusnormal feeding (SDM-N):severely gestational diabetes mellitus, eight pups in lactation; (3) severely gestational diabetes mellitus-overfeeding (SDM-O): severely gestational diabetes mellitus, four pups lactation. At the end of the lactation period, all pups were fed standard laboratory chow adlibitum until the date of the experiments. Offspring body weight was measured weekly after ablactation. Serum insulin was measured by enzyme-linked immunosorbent assay (ELISA) and pancreatic islet morphology was analyzed by immunohistochemistry (IHC) in all three groups at 26 weeks of age. Results (1) Blood glucose of pregnant Wistar rats: SDM (28.3 ±5.1 ) mmol/L was statistically higher than control (6.3 ± 1.4) mmol/L ( P ＜ 0.05 ). (2) Growth rates of body weight in 3 - 7 weeks and 3 - 9 weeks: SDM-N: (4. 6 ± 1.3) % and (6.8±2.5)%, SDM-O:(3.2±0.7)% and(4.6±1.2)%,CG:(2.9 ±0.6)% and(4.1 ±0.8)%.The growth rates of body weight in SDM-N and SDM-O were both significantly higher than those in CG ( P ＜0.05 ). (3) Body weight at 26 weeks: CG: (486 ± 132) g, SDM-N: ( 387 ± 115 ) g, SDM-O: ( 382 ± 122) g.There was no statistical difference among the three groups (P ＞0.05). (4) Fasting plasma glucose ( FPG),fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI): at 26 weeks, the SDM-offspring has nomal FPG, but more insulin was needed to keep it normal. The insulin level of SDM-O[ ( 12.6 ± 3.3) mU/L ] was statistically higher than those of SDM-N [ ( 10.9 ± 3.3 )mU/L] and CG [ ( 8.6 ± 0.8 ) mU/L ] ( P ＜ 0.05 ). The ISI of SDM-O ( 0.020 ± 0.006 ) was significantly smaller than its HOMA-IR(2.40 ±0.62,P ＜0.05). (5)The morphological change of pancreatic islet: The islets of CG and SDM-N were round or ellipse and have clear boundary between endocrine and exocrine parts and the β cells distributed equally. However, SDM-O islets were not of uniform size and most of islets were hyperplasia and hypertrophy. (6) Relative β cell area of pancreas, β-cell area and islet size: SDM-O:(1.81 ±0.31)%, (57.1 ±3.2)% and(39 067 ±3308)μm2; SDM-N:(1.34 ±0.43)%,(60.9 ±0.6)% and ( 30 570 ± 4824 ) μm2; CG: ( 1.11 ± 0.26 )%, ( 63.7 ± 2.7 )% and ( 26 443 ± 4431 ) μm2.SDM-O has significantly increasing β-cell mass, hypertrophic islet size and slightly decreasing β-cell percentage compared with other two groups (P ＜ 0.05 ). Conclusions The exposure of severely hyperglycemia in pregnancy induces low weight infant and postnatal catch-up growth leading to the possibility of insulin resislance (IR) in adult and early postnatal overfeeding will accelerate such course. Islet morphology of SDM-N has no significant change, indicating that maternal diabetes mainly affected β-cell function but not islet morphological features. SDM overfeeding results in early impairment of islet morphology and function, indicating that the compensation ability of islets has already been impaired and the risk of further development of impaired glucose tolerance (IGT) and diabetes. In conclusion, the nutritonal environment in early life ( duration of pregnancy and lactation) participate in the metabolic programming in adulthood.

OBJECTIVE: To investigate the effects of different pattens of intermittent hypoxia on the activity and apoptosis of primary cultured rat embryonic cortical neurons, and to evaluate the role of intermittent hypoxia in the mechanism of obstructive sleep syndrom induced cognitive function loss. METHOD: The embryonic cerebral cortical neurons were cultured in vitro and were identified by immunofluorescence. Cultured neurons were randomly divided into intermittent hypoxia group, intermittent normal oxygen group, persistent hypoxia group and the control group, and intermittent hypoxia group was divided into five subgroups according to different frequency and time-bound. Neurons were exposed in different modes of hypoxia. MTT colorimetry was used to detect the viability of the neurons, and DAPI colorated measurement was used to calculate the percentages of neuron apoptosis. RESULT: There were significantly different effects between all subgroups of intermittent hypoxia and the continued hypoxia group on neuronal activity and apoptosis (P < 0.01); Intermittent hypoxia groups with different frequency and time had no difference in neuronal activity and apoptosis (P > 0.05). CONCLUSION The effect of intermittent hypoxia was more serious than that of continued hypoxia on neuronal activity and apoptosis; The impact of intermittent hypoxia on neuronal activity and apoptosis may be an important factor in obstructive sleep apnea related cognitive impairment.
Animals ; Apoptosis ; Cell Hypoxia ; Cells, Cultured ; Cognition Disorders ; Neurons ; cytology ; Oxygen ; Rats ; Sleep Apnea, Obstructive

Building a medical multimedia teaching resource library is beneficial to distance medical education and the efficiency of multimedia resource usage. Its construction depends on not only modern information technology and the network, but also a comprehensive design from the angle of resource integration.

Objective To investigate the relationship between cognitive impairment and the other clinical features of subcortical damage in patients with magnetic resonance imaging(MRI)-defined subcortical ischemic vascular disease(SIVD).Methods The cohort for this study included 110 SIVD patients who were divided into 3 groups according to cognitive status:patients with noncognition impairment(SIVD-NCI group,n=34),patients with mild cognitive impairment(SIVD-MCI group,n =47) and patients with vascular dementia (SIVD-VaD group,n =29).The cognitive functions were evaluated by the mini-mental state examination (MMSE) and Montreal cognitive assessment(MoCA),the Cambridge cognitive examination-Chinese version(CAMCOG-C),activity of daily living scale(ADL) and clock drawing task(CDT),etc.Depression symptoms were assessed by the geriatric depression scale (GDS),while the other clinical features of subcortical damage were assessed by the timedGet-Up and Go test,etc.Results There were statistically significant differences in the MMSE,MoCA,CAMCOG-C,CDT and ADL scores among the three groups(H=85.36,F=50.32,55.03,H=27.39,40.87,respectively,all P＜0.05).Gait disturbance,urinary disorder,pseudobulbar palsy,depression and falls were statistically significantly different among the threegroups(x2=21.69,21.41,25.51,6.91,21.87,all P＜0.05).In addition,gait disturbance was increasingly aggravated with the severity of cognitive impairment.In SIVD-MCI group,urinary disorder,pseudobulbar palsy and falls were significantly increased as compared with SIVD-NCI group (x2 =15.57,16.31,8.92,both P＜0.017).Depression was statistically significant different between SIVD-NCIandSIVD-VaD group(x2 =6.90,P＜0.017).Among the three groups,there was no significant difference in the feature of emotional incontinence.Conclusions With the decline in cognitive function,the patients with SIVD can present with different clinical features of subcortical damage.Gait disturbance is gradually aggravated with the decline in cognitive function.Urinary disorder,pseudobulbar palsy,and falls can reflect the cognitive impairment from normal to mild on the other hand.Depression can be used as one of the signs that show cognitive impairment reached to dementia.

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.

Testing of hypothesis was affected by statistical analysis set division which was an important data management work before data base lock-in. Objective division of statistical analysis set under blinding was the guarantee of scientific trial conclusion. All the subjects having accepted at least once trial treatment after randomization should be concluded in safety set. Full analysis set should be close to the intention-to-treat as far as possible. Per protocol set division was the most difficult to control in blinded examination because of more subjectivity than the other two. The objectivity of statistical analysis set division must be guaranteed by the accurate raw data, the comprehensive data check and the scientific discussion, all of which were the strict requirement of data management. Proper division of statistical analysis set objectively and scientifically is an important approach to improve the data management quality.

Objective To compare clinical effect and safety of left-double-lumen tube and bron-chial blocker in vedio-assisted atrial fibrillation ablation.Methods Forty-eight patients,26 males and 22 females,aged 45-65 years,ASA physical status Ⅰ or Ⅱ,who underwent vedio-assisted atrial fi-brillation ablation were randomly divided into double-lumen tube (group A)and bronchial blocker (group B),with 24 patients in each group.The tube type of group A was left-double-lumen tube. Bronchofiberscope was used for location in every patient.The mean artery pressure (MAP)and heart rate (HR)before intubation,intubation positioning time,peak airway pressure (Ppeak)after 5 min of one-lung ventilation,lung collapse,incidences of hoarseness,pharyngalgia and choke were ob-served.Results Intubation positioning time between two groups was not statistically significant. MAP and HR were significantly increased at intubation positioning time in both groups,to be specif-ic,they were significantly in group A than in group B (P <0.05 ).When left lungs blocked,Ppeak and qualities of lung collapse were not statistically different between the two groups.When right lungs blocked,group A was higher than that in group B (P < 0.05 ).Cough,hoarseness and sore throat were more frequently seen in group A than in group B.Conclusion Both double-lumen tube and bron-chial blocker can be used in video-assisted atrial fibrillation ablation with satisfying effects.As for the quality of lung isolation,double-lumen tube was better than bronchial blocker.However,compared with bronchial blocker,double-lumen tube results in more unstable hemodynamics and higher occur-rence of hoarseness,pharyngalgia and choke.

Objective:To investigate the in vitro effect of arsenic trioxide (As2O3) alone and in combination with dexamethasone (DXM), etoposide (VP-16), methotrexate (MTX), bortezomib (BTZ), and suberoylanilide hydroxamic acid (SAHA) on the growth of human cutaneous T cell lymphoma (CTCL) cells Hut-78 and Hut-102. Methods:Hut-78 and Hut-102 cells were cultured with different concentrations of As2O3, DXM, VP-16, MTX, BTZ, and SAHA alone and As2O3 in combination with DXM, VP-16, MTX, BTZ, or SAHA for 48 h. The effects of the different samples on Hut-78 and Hut-102 cell proliferation were determined by MTT assay. Analyses using CalcuSyn software were performed to determine whether the combination of As2O3 with DXM, VP-16, MTX, BTZ, or SAHA in-duced synergistic cytoxicity. Results:As2O3, DXM, VP-16, MTX, BTZ, and SAHA alone significantly inhibited the growth of Hut-78 and Hut-102 cells in a dose-dependent manner, with a 50%inhibiting concentration of 5μmol/L, 500μg/mL, 2.5μg/mL, 1μg/mL, 10μmol/L, and 2.5μmol/L individually after 48 h of culture. As2O3 with DXM, VP-16, MTX, BTZ, or SAHA showed remarkable antitu-mor efficacy compared with that of individual applications. Conclusion:As2O3 alone or combined with DXM, VP-16, MTX, BTZ, or SAHA significantly inhibited Hut-78 and Hut-102 cell growth in vitro. This study demonstrated that As2O3 with DXM, VP-16, MTX, BTZ, or SAHA presents synergistic antitumor effects on CTCL cells and may be an optimal regimen in clinical trials of CTCL.

ABSTRACT:Objective To explore the effects of miRNA-1246 (miR-1246)on cell proliferation,invasion and migration in human cervical squamous cell carcinoma (CSCC)cell line SiHa.Methods SiHa cells were assigned into 3 groups:miR-1246 analog group,miR-1246 antagonist group and control group.Transfection efficiency was determined.The MTT assay,transwell assay and wound healing assay were performed respectively to evaluate the proliferation,invasion and migration abilities of SiHa cells.Western blot was carried out to detect the expression of thrombospondin-2 (THBS2)before and after transfection.A THBS2 3’-UTR-containing dual luciferase plasmid was synthesized and co-transfected with miR-1246 into SiHa cells to observe the luciferase enzyme activity.Results MTT assay,transwell assay and wound healing assay revealed that the abilities of proliferation,migration and invasion were significantly enhanced (P<0.01)in SiHa cells transfected with miR-1246 analog,but suppressed in SiHa cells transfected with miR-1246 antagonist.Western blot showed that SiHa cells transfected with miR-1246 analog had significantly decreased THBS2 expression (gray value = 6 .2 8 ± 1 0 .2 2 , P=0 .0 1 3 ) while those transfected with miR-1246 antagonist had significantly increased THBS2 expression (gray value = 12.90±19.81, P=0.037).After co-transfected with miR-1246 and THBS2 3’-UTR-containing plasmid,SiHa cells exhibited a decreased level of luciferase enzyme expression.Conclusion miR-1246 promoted the proliferation,invasion and migration of CSCC SiHa cell, and it might promote CSCC tumorigenesis and progression by suppressing the expression of its target gene THBS2 .

Objective To evaluate the clinical outcome of NB09 (China Pediatric Neuroblastoma cooperative group 09) protocol on children with high-risk and ultra-high risk neuroblastoma. Methods The clinical and follow-up data of pa?tients who suffered from high-risk (n=7) and ultra-high risk (n=31) neuroblastomas and admitted in Tumor hospital of Tian?jin Medical University between January 2009 to January 2013 were retrospectively reviewed (27 boys and 11 girls). The age at diagnosis was 19-160 months (median age was 36.5 months). In the high risk group, patients were evaluated and operated after 4 to 6 circles of neoadjuvant chemotherapy. In ultra-high risk group, patient received chemotherapy before and after op?eration, then autologous stem cell transplantation and tumor bed radiotherapy. After chemotherapy, retinoic acid treatment was given to patients in ultra high risk group as in high risk group. Results At the end of treatment, 25 patients achieved complete remission; 5 patients achieved partial remission; 3 patients were in stable disease;5 patients were deteriorating in their conditions which lead to 2 deaths. In total, the response rate reaches upto 86.8%. By the end of follow up, 15 patients had a disease-free-survival, 9 patients survived with tumor, 7 died from recurrence and 7 died from deteriorating conditions. Survival time ranged from 6 to 52 months (median survival 25.5 months). The 1-, 2- and 3-year overall survival were 91.7%, 64.5%and 57.3%respectively. Kaplan-Meier curve and Log-rank test showed no statistical significance between high risk and ultra-high risk neuroblastomas. Conclusion The outcome of NB09 protocol for high risk and ultra-high risk neuroblastoma was preliminary affirmed. It is worthy of further clinical verification.