Carcinoma, Papillary ; genetics ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics

[Objective] To investigate the effects of platycodin D(PD) on the proliferation and apoptosis of human stomach cancer SGC7901 and the related mechanism.[Methods] SGC7901 was cultured in virto and was treated with 5～20μm·L-1 concentrations of PD.Cell proliferation was examined by MTT assay.Cell apoptosis was detected by Annexin V FITC/PI double staining.The change of mitochondrial trans-membrane potential was measured by JC-1 staining.The potein expression of cleaved caspase-3,cleaved caspase-9,cleaved PARP,bcl-2,bax,p-ERK,ERK,p-JNK,JNK,p-p38 and p38 detected by Western blot.[Results] MTT results showed that PD inhibited the growth of SGC7901 cells in a dose-dependent manner at 24h and 48h.SGC7901 cells treated with PD for 24h showed significantly enhanced apoptosis and weakened mitochondrial membrane potential compared with the control cells.Western blot results showed that PD could up-regulate expression of cleaved PARP,cleaved caspase-3,cleaved caspase-9,bax,p-JNK,p-p38 protein,decreased bcl-2,p-ERK protein,the expression of ERK,JNK,p38 protein did not change significantly.[Conclusion] PD may inhibit the proliferation and induce the apoptosis of SGC7901 cells.These findings indicated that PD inhibited cell proliferation by inhibiting the ERK signaling.PD effect on bax and bcl-2 by activation of JNK and p38 signaling pathway resulted in the decrease of mitochondrial membrane potential and activation of caspase,which induced the apoptosis of cancer cells.

The association of serum nesfatin-1 levels with insulin resistance and pancreatic β-cell function in gestational diabetes mellitus was investigated.Oral glucose tolerance test(OGTT) was performed in ninety pregnant women from 24,to 28 gestational weeks.They were divided into three groups according to OGTT:45 nomal controls,27 gestational diabetes mellitus with fasting plasma glucose (FPG) of 5.1 mmol/L to 7.0 mmol/L (GDM1),18 gestational diabetes mellitus with FPG more than 7.0 mmol/L (GDM2).Serum nesfatin-1 levels were significantly higher in patients with GDM1 and GDM2 than in controls (P＜0.01),and in GDM2 group it was also higher than GDM1 group(P＜0.05).Fasting serum nesfatin-1 was positively correlated with FPG,30 min plasma glucose,1 h plasma glucose,2 h plasma glucose,homeostasis model assessment for insulin resistance,and PGAUC,but negatively correlated with homeostasis model assessment for β-cell function.Furthermore,multiple stepwise regression analysis showed that FPG was the independent influencing factor of serum nesfatin-1 level.Nesfatin-1 was positively correlated with insulin resistance,while negatively correlated with pancreatic β-cell function.Nesfatin-1 may play a role in the pathogenesis of gestational diabetes mellitus.

Objective To observe the expression of novel URB gene in the differentiation display of 3T3-L1 preadipocytes and the effects of interleukin-6 (IL-6) and pioglitazone (PIO) on URB mRNA expression in 3T3-L1 adipocytes at different times. Method The 3T3-L1 adipocytes were treated with IL-6 and PIO under different concentration and different time phase, and real-time fluorescence monitoring RT-PCR was conducted to measure the URB mRNA level. Fat droplets were verified by oil red O staining. Results 1. URB mRNA level was increased gradually in the whole differentiation process. 2. The expression levels of URB mRNA was decreased along with the treatment of IL-6 in a dose-dependent manner in 3T3-L1 preadipocytes and adipocytes. 3. PIO increased the level of URB mRNA in 3T3-L1 adipocytes, and the reducing effect of IL-6 on URB mRNA could be corrected by PIO. Conclusion URB may be an important adipocytokin which affects energy metabolism and may work as a pharmacological gene target in the future.

Objective To study the clinical features and treatment results of hepatic epithelioid hemangioendothelioma (HEHE).Methods A retrospective study was conducted on 26 patients with HEHE who were diagnosed and treated at the Eastern Hepatobiliary Surgical Hospital in Shanghai from November 2003 to December 2015.Results The main clinical manifestations of these 26 patients included abdominal pain (13),dizziness (1),anorexia (1),the other 11 patients were asymptomatic.Ultrasound test revealed mixed echogenicity in 17 patients (17/25,68.0％).CT study showed hypointensity lesions in 10 patients (10/12,83.3％).MRI scans identified T1WI hypointense signals in 12 patients (12/14,85.7％) and T2WI hyperintense signals in 11 patients (11/14,78.6％).Platelet distribution width (PDW) assay indicated 18 patients ＜ 15.5 fl (18/22,81.8％),P ＜0.05.all the patients performed tumor makers test,including AFP,CEA,CA19-9.Slightly elevation of CA19-9 was merely identified in one patient.All the patients were confirmed CD34 positive through immunohistochemistry stains.The 1,3,5-year survival rates of these patients were 87.7％,57.0％,43.4％,respectively.Median survival was 61 months.Conclusions HEHE should be considered based on the suggestive imaging findings for the patients with negative tumor markers after exclusion of hemangioma.PDW assay may have a key role in HEHE diagnosis.

Background Cystoid macular edema(CME) is an important cause of visual impairment of central retinal vein occlusion(CRVO).Spectral-Domain optical coherence tomography(SD-OCT) has increased speed and higher resolution,offering a better chance of understanding the morphological changes and pathogenesis of CME. Objective This study was to survey the morphologic features of macular edema associated with CRVO by SD-OCT. Methods Clinical data of the patients with CRVO diagnosed in Department of Ophthalmology,Peking Union Medical College Hospital from March 2008 to August 2009 were retrospectively analyzed.SD-OCT features of macular edema induced by CRVO were analyzed and recorded.Results The average macular foveal thickness was(527.5±218.2) μm in macular edemas eyes.Main morphological changes included 55 cases(84.6%) of CME,15 cases of(23.1%) serous macular detachment(SMD),and 10 cases(15.4%) of simple macular edema,and these findings occurred at the same time in some eyes.Cystoid spaces in the parafoveal region were seen in the inner nuclear layer,outer plexiform layer and outer nuclear layer,and discontinuous or weak inner segment/outer segment(IS/OS) line was often seen in CME.The incidence of CME associated with incomplete posterior vitreous detachment(PVD) was 14.5%,and that of neural epithelial edema associated with incomplete PVD was 10.0%,showing an insignificant difference between them(χ2=0.000,P=1.000).The average area of SMD was 1838.4μm ×1428.1μm×190.1μm,and the incidence of partial PVD was higher(χ2=4.266,P=0.039).Conclusion SD-OCT can reveal the micro-morphological change of macular zone in macular edema eye.SD-OCT enabled visualization of its spatial extent in each retinal layer and the condition of IS/OS layer.Serous macular edema is related with partial PVD.

On the base of element and metabolism balancing,the mathematic model of the human-like collagen expression phase with recombinant Escherichia coli BL21 was developed and the unknown parameters in the model were estimated with the method of nonlinear optimization.The model was in agreement with the growth kinetics and the metabolic kinetics,and the key calculated parameters of ?h,?p and mx were 1.173 mol?C-mol-1,293.814 mol?C-mol-1 and 17.878 mol?C-mol-1?h-1 respectively.This model could preferably predict the macroscopic reaction rates,and in the synthesis phase of human-like collagen,the specific growth rate should be controlled at 0.04 h-1 with controlling glucose feeding rate to gain the highest specific production rate of human-like collagen.

Objective To explore the relationship between Stathmin-1 and human papilloma viruse (HPV) persistent infection after conization of uterine cervix, and to show the clinical significance to recurrent of cervical intraepithelial neoplasia (CIN). Methods One hundred and six patients who were treated with conization of uterine cervix for CIN 2-3 grades were enrolled. Thirty-six recurrent patients were enrolled in recurrence group, and the others were enrolled in control group. The expression of Stathmin-1 in primary CIN tissues in two groups was detected by immunohistochemistry. The HPV infection was detected by HPV-DNA test. The relationship of HPV persistent infection and recurrence was analyzed. Results The positive expression rate of HPV persistent infection and HPV persistent infection rate in recurrence group were 88.89%(32/36), 83.33%(30/36), in control group were 34.29%(24/70) and 22.86%(16/70), and there were significant difference (P <0.01). Forty-two patients had HPV persistent infection in 56 patients with stathmin-1 positive expression, and 4 patients had HPV persistent infection in 46 patients Stathmin-1 negative expression. There was positive correlation (r=0.97, P<0.01). The type of HPV persistent infection in two groups was no significant difference (P >0.05). Conclusions Stathmin-1 positive expression is related to HPV persistent infection. The two factors can affect the prognosis of high-grade CIN, and can provide new cues and theory basis for the prevention of recurrence.

Objective To research the antiviral activity of artesunate (ART) in vitro fighting against both standard laboratory strains and ganciclovir(GCV)-resistance strains of human cytomegalovims(HCMV) and to explore whether fractionation dosage method can obviously enhance the antiviral effect of ART.Methods 1.Cytotoxicity assay to ART was performed by the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetry.The 0％ toxic concentration (TC0) were determined,and median cytotoxic concentration (TC50) was calculated with Probit regression method.2.Antiviral activity assays of ART against HCMV:human embryonic lung fibroblast cells (HELs) were infected with standard laboratory strains and GCV-resistance strains of HCMV,respectively,after which virus was removed and overlays of dulbecco's modified eagle medium(MEM) containing different antiviral drugs were added to the wells.All cells were cultured continuously at 37 ℃ in a 50 mL/L CO2 humidified atmosphere for 7-10 days and the cytopathic effect (CPE) was observed under a microscope.When the degree of CPE was clear (+ + +-+ + + +),the values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The cell survival rate (CSR)and drug inhibitory rate (IR) for HCMV were calculated.By Probit regression method,the median inhibitory concentration (IC50) of 2 drugs was calculated respectively.3.To explore whether fractionation dosage method could obviously enhance the antiviral effect of ART against HCMV,the experiment was divided into 3 groups and compared with GCV group,respectively:Group 1:ART antiviral compounds were added to cell layers by one dosage.Group 2:Total drug dosage was divided into 3 parts,and each part was added to cell layers once a day for 3 days.Group 3:Total antiviral compounds were divided into 6 and delivery 2 times a day.The values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The CSR and viral inhibitory rates were calculated.All data were statistically analyzed by One-Way ANOVA analyzing using SPSS 18.0 statistical software.P value of ＜0.05 was considered to indicate statistical significance.Results 1.Cytotoxicity assay showed that cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.TC0 and TC50 value of ART were 62.5 μmol/L and 171.7 μmol/L.2.In concentration of 5 μmol/L,15 μmol/L and 30 μmol/L,ART and GCV could obviously inhibit growth of HCMV AD169 strains.There was no significant difference between them.The value of GCV IC50 was 3.49μmol/L,and the value of ART IC50 was 2.17 μmol/L.Treatment index (TI) of ART was 28.8,and GCV was 716.3.ART could still obviously inhibit growth of HCMV resistant strains,but GCV couldn't.Differences between them were statistically significant.The value of GCV IC50 to HCMV resistant strains was 44.4 μmol/L,and the value of ART IC50 was 2.5 μmol/L.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.Difference was statistically significant(P ＜ 0.01).GCV delivered as the same method had little different changes in virus suppression ratio(P ＞ 0.05).Conclusions 1.Cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.2.ART could obviously inhibit growth of HCMV resistant strains and standard laboratory strains.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.4.Because the action mode of ART is different from other anti-HCMV drugs,and ART has a high biological activity and fewer side effects,it is expected to become a kind of new antiviral drugs for HCMV infections.

Objective To investigate whether Ulinastatin (UTI) would minimize the systemic inflammatory response,lessen cardiac dysfunction and protect neurons against injury in hippocampus CA1area after restoration of spontaneous circulation (ROSC). Methods Animal models of cardiac arrest were established in 24 New Zealand rabbits,and those animals were randomly (random number) divided into control group and UTI treated group after ROSC.Changes in the levels of plasma inflammatory cytokines TNF-α and IL-6 were assayed before cardiac arrest and 4,8,12 and 16 hours after ROSC.Cardiac function including FS,EF and E/A were observed with ultrasonography before cardiac arrest and 4,8,12 and 16hours after ROSC,and viable and apoptotic neurons in hippocampus CA1 area and infiltrations of MPO positive cells in myocardium,cerebrum,liver,kidney and intestine were counted 72 hours after ROSC.The t-test or Mann-Whitney rank sum test was used to verify the specified theoretical distribution functions of the biomarkers tested by Kolmogorov-Smirnov test,POST HOC test was used for the multiple comparisons,and Pearson correlation analysis was used to investigate the correlation between inflammatory cytokines and cardiac function. Results The levels of TNF-α and IL-6 in UTI group were lower than those in control group as those data got 4,8,12 and 16 hours after ROSC (P ＜0.05).EF and E/A in UTI treated group were higher than those in the control group as those data got 4,8,12 hours after ROSC.FS values obtained 4 h and 8 hours after ROSC were higher in UTI group than those in control group ( P ＜ 0.05 ).The Pearson correlation analysis showed that the levels of TNF-α and IL-6 significantly correlated with EF after ROSC.The number of viable neurons in CA1 area of control group was ( 13.22 ± 0.97) which was lower than that in UTI group ( 16.89 ± 1.45 ) ( P =0.003 ),while the number of apoptotic neurons in hippocampus CA1 area was higher in control group than that in UTI group (15.67 ± 1.37) vs.(13.67 ± 1.03 ) (P =0.019).The numbers of MPO positive cells were significantly lower in liver,kidney and intestine in group UTI than those in control group. Conclusions UTI could inhibit the infiltration of MPO positive cells in liver,kidney and intestine,decreasing the levels of TNF-α and IL-6 in plasma,in turn lessening cardiac dysfunction and protecting neurons from injury in hippocampus CA1 area after ROSC of New Zealand rabbits.