Background Inflammation and adipogenesis are two parallel processes with increasing activity in severe thyroid-associated ophthalmopathy(TAO),and mevastatin was proved to have the inhibiting effect on the differentiation of adipose.Objective The aim of this work was to investigate the effects of mevastatin on the expression of cyclooxygenase-2(COX-2)and peroxisome proliferator activated receptor-γ(PPAR-γ)and differentiation of TAO-derived orbital preadipocytes,and explore its modulation effects on lipopolysaccharide(LPS)induced inflammation and the differentiation of TAO-derived orbital preadipocytes in vitro.Methods The retroorbital adipose tissue was obtained from 4 TAO patients during the surgery.The orbital fibroblasts were cultured from orbital adipose tissues using explant culture method.To study the suppressing effect of mevastatin on inflammatory response,cultured cells were divided into 5 groups.The 1000 μg/L LPS orbital fibroblasts were stimulated for 8 hours in group A,and 1000 μg/L LPS combined with 5 μmol/L,10 μmoL/L or 20 μmoL/L mevastatin were used respectively for the substitute in the group B,group C and group D.The orbital fibroblasts in group E were cultured routinely without any intervention as control.To observe the inhibiting effect of mevastatin on the differentiation of adipose,the group A were then subdivided into group A1-A6.After 1000 μg/L LPS was used to treat the cells for 8 hours,the ceils were induced to differentiate into adipocytes.All orbital preadipocytes from A1 to A6 were stimulated to differentiate into mature adipocytes with cocktail differentiation medium for a 10-day duration.During the procedure,group A2,A3 and A4 were interfered with 5,10 or 20 μmol/L mevastatin,and in the group A5 and A6,10 μmol/L mevastatin were added at the fourth day or eighth day.Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining.The absorption(A492 nm)was measured in the ceils by enzyme-linked immunosorbent assay(ELISA).Expression of COX-2 and PPAR-γ mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR),and the expression of COX-2 and PPAR-γ protein was detected by Westernblot.The level of PGE2 in the supernatant was detected by ELISA.Results The expression of COX-2 protein and mRNA as well as the PGE2 levels in B,C,D group decreased markedly in comparison with those in A group(P＜0.05).With the increase of mevastatin concentration,the expression of COX-2 protein and mRNA as well as the PGE2 levels in B,C,D groups decreased successively(F =228.380,101.745,1586.881,P＜0.05).The expression of COX-2 protein and mRNA and PGE2 levels in E group were lower significantly than those in A,B and C groups(P＜0.05),but no significant differences were found between E group and D group(P＞0.05).The A492 value and the expressions of PPAR-γ protein and mRNA in differentiated cells showed the successively decrease in A1-A4 group with the elevation of mevastatin concentration(P＜0.05),and the evidently decreased A492 value and the expressions of PPAR-γ protein and mRNA also were seen in A1 and A5 groups compared with A3 group(P ＜ 0.05).Conclusions Mevastatin inhibits LPS-induced COX-2 expression,PPAR-γ expression,PGE2 secretion and differentiation of TAO-derived orbital fibroblasts in vitro in dose-dependent manner.Mevastatin plays these effect more prominently in early stage of adipocytes differentiation.

Objective To compare of the effect of intravenous zoledronic acid and calcitonin on the elderly with osteoporotic intertrochanteric fractures.Methods From June 2009 to November 2012,610 patients with osteoporotic intertrochanteric fractures were treated with closed reduction and internal fixation.543 consecutive patients were grouped sequentially according to the admission time.From June 2009 to April 2011,control group (n=325)received calcitonin for osteoporosis (male 107,female 218,mean age 75.02±5.65 years).The number of Evans-Jensen type Ⅰ,Ⅱ,and Ⅲ type patients were 87,136,and 102,respectively.Average lumbar bone mineral density (BMD) and hip BMD were 0.737±0.08 g/cm2 and 0.725±0.05 g/cm2,respectively.From May 2011 to November 2012,218 patients (male 82,female 136,mean age 74.71±5.32 years) received zoledronic acid for osteoporosis.The number of Evans-Jensen type Ⅰ,Ⅱ,and Ⅲ type patient were 62,91 and 65,respectively.Average lumbar BMD and hip BMD were 0.738±0.05 g/cm2 and 0.722±0.06 g/cm2,respectively.All patients received once-yearly intravenous zoledronic acid in one week after operation.The BMD during hospitalization and one year after operation were compared between the two groups.Harris score and VAS score were applied to evaluate the function and pain degree of the operated hip joint.Results The average follow-up time were 12.8 months (range,5 to 22 months) in control group and 12.5 months (range,4 to 19 months) in treatment group.The average fracture union time,Harris score,VAS score were 14.25±1.38 weeks,68.88±5.71 points,and 0.36±0.55 points respectively in treatment group and 14.39± 1.12 weeks,69.47±4.60 points,and 0.33±0.48 points respectively in control group.There were no statistical differences between two groups in fracture union time,Harris score and VAS score.The average lumbar BMD and hip BMD were 0.76±0.06 g/cm2 and 0.75±0.04 g/cm2 in treatment group,which were 0.75±0.07 g/cm2 and 0.74± 0.07 g/cm2 in control group one year after operation,respectively.Compared with the baseline,the BMD of lumbar spine and hip one year after operation slightly increased without statistically significant difference in control group.The BMD increased significantly in treatment group.Conclusion Early administration of intravenous zoledronic acid does not influence bone healing and it could increase BMD one year after closed reduction and internal fixation.

Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P ＜ 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.

Objective To evaluate the effect of transcatheter arterial chemoembolization (TACE) and delayed surgery for infant hepatoblastoma.Methods TACE was performed with the initial digital subtractive angiography (DSA) under general anesthesia 1-3 times in 8 infants with huge hepatoblastoma, whose age was 2 to 12 months. DSA was done via arterials in hepatoblastoma each time before chemoembolization. The arterials were perfused with chemodrugs and suspensions in ultrasome iodized oil , and were blocked with spring rings. DSA findings indicated that the tumor shrank without new tumorous arterials after 1 month in 6 cases, and 4 of them showed no tumorous staining, and the delayed surgery was performed successfully 1 week later in 6 infants. One boy underwent systemic chemotherapy alone during 6 months after 3 times of TACE. Results TACE therapy did not encounter any major technical problem or toxic reaction caused by chemotherapy. The following DSA test 4 weeks later did not detect any new tumorous vessels in 6 cases. Six children received TACE and surgery had been followed-up with no tumor recurrence for months averagely. The boy underwent TACE and venous chemotherapy for 6 months , without surgery , had been followed-up for 48 months until the present report. CT, AFP and DSA did not show any hints of tumor recurrence. Six cases receiving 3 times TACE combined with surgery survived without tumor recurrence. Conclusions TACE is a very effective, safe and helpful therapy for hepatoblastoma, which stressed the repeated use of spring ring to block tumor vessels lastingly if necessary. If surgery is required, DSA test is needed beforehand to detect new tumorous vessels or neoplasm. If there is any , TACE is repeated. TACE combined with surgery may provide an additional promising choice in the treatment of hepatoblastoma, and repeated TACE alone may cure hepatoblastoma in infants.

Objective To explore the clinical significances of blood gas and dynamic monitor of respiratory mechanics in respiratory failure children with mechanical ventilation.Methods Sixty-four children who need mechanical ventilation over 24 hours were divided into pulmonary disease group(44 cases) and non-pulmonary disease group(20 cases) in pediatric intensive care unit(PICU),from Jan.2005 to May 2008.By Evita 4 ventilator,dynamic monitor of respiratory mechanics,such as respiratory system compliance(Crs),airway resistance(Raw),mean airway pressue(MAP),minute ventilation(MV),oxgen index(OI),Qs/Qt,respiratory index(RI) and blood gas in these children were determined.Their characteristics and clinical significance were analyzed.Results Many parameters such as Crs,Raw,MAP,MV,Qs/Qt,OI,RI were significantly different between 2 groups(Pa

Objective To observe the effect of high iodine on mRNA expression of thyroid hormone receptor (TSHR),protein kinase A (PKA) and sodium iodide symporter (NIS) in peripheral blood of patients with thyroid diseases during lacatation.Methods A total of 99 breast-feeding women were selected as observation objects in Shanxi Province's sufficient iodine and high iodine areas,and they were divided into case group and control group according to whether suffer from thyroid disease.In high iodine areas,there were 21 patients and 19 healthy controls.In sufficient iodine areas,there were 30 patients and 29 healthy controls.Peripheral blood of all the observation objects was collected,and mRNA expression of TSHR,PKA and NIS was detected by real-time quantitative PCR.Results The case group [median (M):0.099,0.994] and the control group (M:0.240,0.738) in the high iodine areas were respectively compared with the case group (M:3.087,1.127) and the control group (M:1.823,0.842) in the sufficient iodine areas.The TSHR mRNA expression was significantly decreased (Z =-5.034,-4.010,all P ＜ 0.01);the PKA mRNA expression had a downward trend,and the difference was not statistically significant (Z =2.895,-0.343,all P＞ 0.05).The NIS mRNA expression of the case group in high iodine areas (M:0.485) was obviously lower than that of the the case group in sufficient iodine regions (M:2.680,Z=-3.311,P ＜ 0.01).The control group in high iodine areas (M:0.470) was compared with the control group in sufficient iodine areas (M:0.835),and the difference was not statistically significant (Z =-1.882,P ＞ 0.05).The NIS and the TSHR mRNA were positively correlated [correlation coefficient (r) =0.741,P ＜ 0.01];the NIS and the PKA mRNA was also positively correlated (r =0.293,P ＜ 0.01);but the TSHR mRNA was not significantly correlated with the PKA mRNA (r =-0.081,P ＞ 0.05).Conclusion Lactating women may have protected themselves and their babies through TSH-TSHR-cAMP-PKA signaling pathway that regulating iodine levels.

Analysis is made to the necessary of interdisciplinary,and point four sections should be concerned when begin to construct the interdisciplinary in general hospital which are short term profits and long term culture,personal development and team building,the passion of the young and the leadership of the old,the cooperation with the science and engineering and the communicate with the humanities.At last it also lists the steps and main points on how to begin the construction of interdisciplinary in general hospital.

Objective To observe the variation of phosphatidylinositol-3 kinase (PI3K),protein kinase B (AKT),sodium iodide symporter (NIS) mRNA and protein expression in rat mammary tissues and serum insulin growth factor Ⅰ (IGF-1) under different iodine nutrition levels,and to study the role of PI3K-AKT signaling pathway in the process of mammary gland intaking iodine during lactation period.Methods Totally 130 Wistar rats (100 female rats,30 male rats) were randomly divided into five groups with 20 female rats in each group:①control group (NI):was feed with normal diet and iodine content 50 μg/L in deionized water;②low iodine group 1 (LI1 group):was feed with low iodine diet and deionized water;③low iodine group 2 (LI2):was feed with low iodine diet and iodine content 5 μg/L in deionized water;④high iodine group 1 (HI1 group):was feed with normal diet and iodine content 3 000 μg/L in deionized water;⑤high iodine group 2 (HI2):was feed with normal diet and iodine content 10 000 μg/L in deionized water.After feeding for 3 months,females were mated with male rats,then male rats were taken out and every female rat was feed individually.Urinary iodine level of rats in lactation period 10 days after giving birth was tested.Blood and mammary tissue samples of rats in lactation period were taken after killing them.Enzyme linked immunosorbent assay (ELISA) was used to detect serum IGF-1 level,real-time fluorescence quantification PCR to detect the mRNA expression of mammary gland PI3K,AKT and NIS,Western blotting to detect mammary gland PI3K,total AKT,phosphorylation AKT (p-AKT) and NIS protein expression.Results The medians urinary iodine of lactation period rats in LI1 and LI2 (3.16,6.36 μg/L) were significantly lower than that in NI group (162.59 μg/L),and were significantly higher in HI1 and HI2 (2 356.27,11 507.29 μg/L) than that in NI group.The differences were statistically significant (all P ＜ 0.01).Compared with control group [(8.84 ± 2.12) μg/L],the content of serum IGF-1 increased significantly in lactation period rats in LI1 and LI2 groups [(13.30 ± 2.37) and (10.90 ± 1.92) μg/L,all P＜ 0.01].The real-time fluorescence quantification PCR detection results indicated that the differences were statistically significant by comparing NIS,AKT,PI3K mRNA expression of the mammary tissues of lactation period rats in the five groups (F=14.916,36.477,14.994,all P＜ 0.01).Among them,NIS mRNA expression quantities in LI1 and LI2 groups (0.75 ± 0.40,0.89 ± 0.51) were significantly higher than that in NI group (0.53 ± 0.31),and significantly lower in HI2 group (0.30 ± 0.24) than that in NI group (P ＜ 0.05 or ＜ 0.01).AKT mRNA expression quantities in LI1 and LI2 groups (0.90 ± 0.19,0.64 ± 0.22) were significantly higher than that in NI group (0.43 ± 0.22),and significantly lower in HI2 group (0.29 ± 0.15) than that in NI group (P ＜ 0.05 or ＜ 0.01).PI3K mRNA expression quantity in LI1 group (0.85 ± 0.42) was significantly higher than that in NI group (0.50 ± 0.24),and significantly lower in HI2 group (0.28 ± 0.10) than that in NI group (all P ＜ 0.01).Western blot detection results indicated that the differences were statistically significant by comparing mammary gland NIS protein expression of lactation period rats in the five groups (F=4.510,P＜ 0.01).Among them,LI1 group (1.67 ± 0.97) was significantly higher than NI group (0.87 ± 0.43,P ＜ 0.05).The differences were statistically significant by comparing the p-AKT protein expression among groups (F =3.528,P ＜ 0.05).Among them,HI2 group (1.10 ± 0.30) was significantly higher than NI group (0.75 ± 0.23,P ＜0.05).The differences were not statistically significant by comparing total AKT and PI3K protein expression among groups (F =0.558,1.319,all P ＞ 0.05).Conclusion The inhibitory effect of PI3K-AKT signaling pathways on NIS in the mammary gland was weaker than the effect of iodine intake.But the expression of functional p-AKT was gradually increased with the increment of iodine intake,which had been presented inhibit effect on NIS expression in lactating mammary gland.

Objective To analyze the influence of SH3 domain mutant (ABL SH3-T79Y) in BCR-ABL protein of chronic myeloid leukemia (CML) in combination with imatinib (IM) on the proliferation of CML cells in vivo and vitro, and to discuss the mechanism thereof. Methods Recombinant ABL SH3-T79Y mutant adenovirus vectors which were successfully constructed in previous work was used with IM to treat K562/G01 cells, then the cell-colony forming ability of K562/G01 cells was determined by clone formation assay, and cell cycle was assessed by flow cytometry. KCL22 cells were treated by recombinant SH3-T79Y and IM to construct subcutaneous solid tumor model in Balb/c nude mice, then the formation rate of subcutaneous tumor was estimated, the pathological examination was conducted, and the proliferation ability of KCL22 cells was assayed. K562/G01 cells were treated by SH3-T79Y and IM in combination, and the expression levels of p-BCR-ABL, BCR-ABL, p-CrkL, CrkL and Cyclin-D1 protein were determined by Western blotting. Cells treated with PBS, null recombinant adenovirus vectors or IM alone served as control groups. Results Compared to the 3 control groups, clone forming rate of K562/G01 cells decreased significantly (P<0.05) and cell cycles were arrested at S phase after being combined SH3-T79Y and IM treatment. The subcutaneous solid tumor formation rate in KCL22- Balb/c nude mice was 16.7% after combined SH3-T79Y and IM treatment, and large number of tumor cells were observed in tumor pathology examination. Western blotting revealed that the expression levels of p-BCR-ABL, p-CrkL, BCR-ABL, CrkL and Cyclin-D1 were decreased in K562/G01 cells. Conclusion Combined treatment of SH3-T79Y and imatinib may inhibit the proliferation of CML cells in vivo and in vitro by decreasing BCR-ABL and CrkL phosphorylation as well as Cyclin-D1 protein.

CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.
ADP-ribosyl Cyclase 1 ; antagonists & inhibitors ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; Humans ; Purines ; chemical synthesis ; chemistry