Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers.

Female ; Humans ; Infant ; Infant, Newborn ; Larynx ; abnormalities ; surgery ; Male ; Respiratory System Abnormalities ; surgery ; Vocal Cords ; abnormalities ; surgery

Objective To investigate the effect of 17β-estradiol on the proliferation of thyroid stem/ progenitor cells.Methods In thyroid stem/progenitor cells derived from nodular goiters,the effects of 17 β-estradiol on thyrosphere formation,estrogen receptor (ER) expression,cyclin D1 expression,and mitogen activated protein kinase (MPAK) pathway were analysed by BrdU ELISA,conventional and realtime PCR,immunofluorensence staining,and Western blot.Results 17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/ progenitor cells.ER-α and ER-β were expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-α compared to differentiated thyrocytes (8.85-±0.81 vs 1.10 ±0.35,P＜0.01).Stimulation by 1 mmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels,which was blocked by an ER antagonist,ICI 182780.Conclusion Estrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor,suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.

Objective:To detect the change of composition of immune cells in the spleen of miR-126 knockdown(miR-126KD) mice and preliminarily explore its significance .Methods: The expression level of miR-126 in spleens of miR-126KD mice was deter-mined by Realtime PCR.And the total number of splenocytes was calculated.The pathologic morphology change of the spleen was observed by HE staining.And the changes on proportion of DCs ,macrophages cells ,γδ T cells and NK T cells,CD3+T cells and its subgroup ,as well as CD19+B cells in spleens of miR-126KD mice were analyzed by Flow cytometry and calculated respectively.The level of phosphorylated AKt and NF-κB was analyzed by Western blot assay.Results:Compared with those of WT mice ,the expression level of miR-126 decreased obviously ( P<0.05 ) and the total number of cells increased obviously in spleen of miR-126 KD mice ( P<0.05).Moreover,the pathologic morphology of miR-126KD mice was significantly changed.The proportion and number of NK T cells in the inherent cells were significantly increased ( P<0.05 ) , but the proportion of Mφcells were significantly decreased ( P<0.05 ) . Meanwhile,the proportion and number of CD3+T cells and CD4+T cells in the adaptive immune cells were significantly increased (P<0.05),while the total number of CD19+B cells were significantly decreased (P<0.05).Last,the level of phosphorylation Akt and NF-κB increased obviously in spleen of miRNA-126 knockdown mice.Conclusion: Change obviously on the composition of immune cells subsets in the spleen of miRNA-126 knockdown mice ,which it may be related to the altered level of phosphorylated AKt and NF-κB and provides a preliminary experimental basis for the further exploring the roles of miR -126 in immune response.

Objective To study whether abnormalities can be detected by MR diffusion tensor imaging (DTI) technology in radiologically isolated syndrome (RIS) patients with normal-appearing white matter (NAWM).Methods Twenty-seven patients who met diagnostic criteria for RIS were collected.Sixteen age-and sex-matched healthy controls with normal neurologic examination findings and no history of neurologic or psychopathic disorders were included.All subjects were examined by both conventional scan and DTI scan on GE Signa 3.0 T MRI.All the images were transmitted to the Advantage Workstation 4.2P and postprocessed using functool software.Anisotropic maps and average diffusion coefficient (ADC) maps were reconstructed.Two ROIs were selected in the genu and splenium of the corpus callosum separately at the trigone of lateral ventricle level.Other 2 ROIs were selected in the anterior and posterior body of the corpus callosum separately at the level of the lateral ventricle body,and 1 ROI was selected in the white matter of bilateral frontal and occipital lobe separately,then the FA and MD values were measured.The diffusion indices (FA and MD)were analysed by SPSS 13.0.Independent-sample t test was performed to examine the group differences in each subregion.Intraclass correlation coefficient analysis was performed to assess the diffusion indices of two measurements in each subregion.Results The ICC of 2 measurements was 0.934-0.989 (P ＜ 0.01),which showed favorable consistency.The FA values were decreased obviously in the genu,anterior and posterior body of the corpus callosum of the RIS patients compared with controls (0.705 ±0.040 vs 0.738 ±0.045,0.632 ±0.043 vs 0.675 ±0.042,0.628 ±0.043 vs 0.666 ± 0.045,t =-3.526,-4.487,-3.890,P ＜0.01),but the FA values of the two groups did not show any significant difference in the splenium,the white matter of the frontal and occipital lobe respectively (t =-1.387,-0.683,-1.243,P ＞0.05).In comparison with controls,the RIS patients had increased MD values in the genu,anterior and posterior body of the corpus callosum.(0.891 ±0.038 vs 0.874 ±0.035,0.839 ± 0.047 vs 0.794 ± 0.031,0.833 ± 0.039 vs 0.792 ± 0.057,t =2.101,5.836,5.146,P ＜ 0.05),but the MD values of the two groups did not show any significant difference in the splenium,the white matter of the frontal and occipital lobe respectively (t =1.671,1.702,1.624,P ＞ 0.05).Conclusion The NAWM abnormalities in the patients with radiologically isolated syndrome could be detected by DTI.

In this paper, Fourier transform infrared spectroscopy fingerprint analysis of Marsdenia tenacissima samples was used to develop a reliable method of tracing the geographical origins. Forty-eight samples from four provinces of China were analyzed by FTIR. We analyzed and characterized the fingerprints in both the full spectrum peaks and characteristic peaks, then the principal component analysis and the cluster analysis were carried out. The results of fingerprint analysis, correlation analysis, principal component analysis and cluster analysis can identify the geographic origins correctly, which verified and supplemented each other; the identification results and the actual location showed a high degree of consistency, namely the lower the space distance, the greater the similarity of different samples. These results revealed the obvious superiority and practical value in comparison to the more tedious and time-consuming wet chemistry method normally used. Using appropriate metrology methods can trace the geographical source correctly. The M. tenacissima materials from the region of Maguan should be considered as genuine medicinal materials taking into account the good quality.
China ; Cluster Analysis ; Drugs, Chinese Herbal ; analysis ; classification ; standards ; Geography ; Marsdenia ; chemistry ; classification ; Medicine, Chinese Traditional ; Principal Component Analysis ; Quality Control ; Reproducibility of Results ; Spectroscopy, Fourier Transform Infrared ; methods

[Summary] The aim of this study was to investigate the changes of sex hormone in male patients with type 2 diabetes and complicated with non-alcoholi fattty liver disease (NAFLD),and to detect the characteristics of the metablic indexs.A total of 112 patients were enrolled and divided into NAFLD group (n =54) and non-NAFLD group (n =58).All patients were measured for waist circumference,body mass index,metablic index,sex hormone,and serum transaminase.Compared with non-NAFLD group,the levels of fasting blood glucose,2 hour postprandial blood glucose,HbA1C in NAFLD group were significantly elevated [(8.75 ± 2.58 vs 7.79 ± 1.89) mmol/L,(18.12 ± 3.95 vs 15.63 ± 3.89) mmol/L,(11.96 ±4.85 vs 10.05 ±4.15)％,all P＜0.05].In addition,total cholesterol,triglyceride,body mass index,fasting insulin,and postprandial insulin in NAFLD group were significantly elevated [(4.97± 1.02 vs4.15±0.92) mmol/L,(2.74±2.25 vs 2.01± 1.45)mmol/L,(27.34±3.93 vs 22.38±3.39) kg/m2,(9.62 ± 5.80 vs 6.18 ± 4.21) μIU/ml,(72.71 ± 109.70 vs 31.72 ± 42.27) μIU/ml,all P＜0.05];while the total testosterone and free testosterone were lowered dramatically[(14.18 ±6.39 vs 18.21 ±6.14) nmol/L,(0.32 ± ± 0.03 vs 0.39 ± 0.08) ng/dl,both P＜0.05].Male patients with type 2 diabetes mellitus complicated with NAFLD are more prone to have disturbance in the lipid metabolism and had larger percentages of obesity and with lower level of testesterone.

Objective To analyze the clinical features of rectal and perianal inflammatory myofibroblastic tumor and evaluate its diagnosis and treatment.Method Clinicopathological data of 3 cases diagnosed as inflammatory myofibroblastic tumor from January,2005 to June,2011 were retrospectively reviewed.Results Inflammatory myofibroblastic tumor presents as infiltrative growth mass with rich vascularization on CT or MRI,and is difficult to distinguish from hemangioma and other rectal tumors.Preoperative biopsy usually fails to ascertain the entity of mass,and pathological examination of the whole resected specimen with immunohistochemical staining is needed to make final diagnosis.All 3 cases underwent sphincter preserving surgery.One case received a second radical operation 16 months after primary resection because of local recurrence.All patients are followed up to now,with a survival time of 67 months,55 months,and 35 months respectively.Conclusions Rectal and perianal inflammatory myofibroblastic tumor is difficult to diagnose on preoperative imaging examinations or biopsy.Immunohistochemical staining is needed to make final diagnosis.Sphincter preserving surgery with complete tumor removal could achieve long term survival.

Objective To report the experience and results in comparing laparoscopic radical nephrectomy (LRN) and open radical nephrectomy (ORN) in the treatment of clinical T_2 stage renal cell carcinomas. Methods Between Feb. 2004 and Jul. 2007, 30 patients (12 females and 18 males with average age of 58.0±8.5 years, range 42-68 years) received LRN and 36 patients (16 females and 20 males with average age of 60.0±9. 0 years, range 52-70 years) received ORN. The average tumor sizes in the LRN and ORN groups were (8. 5±2.2)cm (range 7-12 cm) and (8. 8±2.1)cm (range 7-14 cm) respectively. Renal cell carcinoma was histopatologically confirmed in all the patients of these 2 groups after surgery. Results The operative time in the ORN group (130±27 min) was significantly shorter than that in the LRN group (176±23 min), P<0. 01. The estimated blood loss in the LRN group (200±80 ml) was also significantly less than that in the ORN group (380±185 ml) , P<0. 01. Patients in LRN group experienced significantly earlier bowel function recovery (P<0. 01) and shorter duration of drainage (P<0. 01) than those in the ORN group after operation. No severe perioperative complications occurred in all patients. The follow-up range was 6-27 months (average 15±2 months). During the follow-up, 2 patients in the LRN group developed lung metastasis. In the ORN group, 2 patients developed liver metastasis and 1 developed lung metastasis. Conclusion LRN has the advantages of minimal invasiveness and rapid postoperative recovery comparable to those of ORN, and it might be an alternative treatment option for the clinical T_2 stage renal cell carcinomas.

[Summary] To determine how endocrinologists in China access and treat patients with Graves' orbitopathy (GO) and gain insight on how to make the management of this disease more uniform and standardized in the context that management of GO continues to be challenging.Based on the questionnaire used in the European survey on GO,a questionnaire in Chinese was drafted and circulated to the members of Chinese Society of Endocrinology (CSE).There were a total of 124 valid responders.The majority (94.4％) of the responders believe that a muhidisciplinary approaches for GO management is valuable.Over 80％ of the participants advocated the evaluation of exophthalmometry,vision,visual fields by perimetry,eye movements,fundoscopy,TSH receptor antibodies,thyroid function,and ultrasound.Steroids were preferred as the first-line therapy by 92.7％ of responders,among them,59.7％ choose intravenous route.The treatment strategy for GO with intravenous glucocorticoids therapy still remains debated.Antithyroid drugs were the most common choice (72.6％) for first-line therapy of thyrotoxicosis.Treatment options for GO were very similar among Chinese,Latin-American,and European responders,though radioactive iodine and surgical treatment were more often indicated in China.The appropriate treatment of the patient with GO is controversial even amongst thyroid specialists.Further training of clinicians,easier access of patients to specialist multidisciplinary centres,and the publication of practice guidelines may help improving the management of this condition in China.