Forty-two hyperthyroid patients with mild hepatic dysfunction were treated with 131I once orally and followed up for 6 months. The changes of hepatic functions (ALT, AST, ALP, A/G) were determined before and after treatment, hepatic function was ameliorated in these patients. The results indicate that 131I-iodine is safe and effective in treating hyperthyroidism with mild hepatic dysfunction.

Objective To explore the correlation between quantitative value of joint bone scan by single photon emission computed tomography (SPECT) and serum bone metabolic markers in patients with active rheumatoid arthritis (RA).Method Clinical data of 60 newly diagnosed RA patients were retrospectively collected in Department of Rheumatology and Immunology from May 2013 to December 2014,including 28 cases with medical history less than 6 months and 32 from 6 months to 2 years.Serum Cterminal telopeptide of type Ⅰ collgen(CTX-Ⅰ)and N-terminal propeptide of type Ⅰ collagen(PINP) were tested by chemiluminesence.SPECT whole body bone and target joint scan before treatment was done.Thirty-nine healthy subjects as control group received ultrasound,electrocardiogram,X-ray,and whole body bone imaging examination.Quantitative values of joint imaging were calculated for the statistical analysis.Result Demographic data between RA group and control group were comparable (P ＞ 0.05),including sample,sex,age and BMI.The joint SPECT value,CTX-Ⅰ and PINP levels were all significantly higher than those of control group (P ＜ 0.01),which were 6.48 ± 1.98 versus 3.73 ± 1.t6;(0.66 ± 0.37) mg/L versus (0.58 ±0.21) mg/L;(46.35 ±28.15) mg/L versus (30.47 ± 13.75) mg/L respectively.Joint SPECT values had positive correlations with serum CTX-Ⅰ levels in all RA patients,as well as PINP in patients with disease duration 6mon-2years.And the according correlation coefficients were 0.513,0.495,0.402 (P ＜ 0.05).But SPECT value had no correlation with CTX-Ⅰ (P =0.081) in patients with disease duration less than 6 mon.The correlation coefficient was 0.336.Conclusion SPECT imaging quantitative values were positively correlated with serum bone metabolic parameters.Thus SPECT imaging alone or combined with bone markers are helpful in diagnosing active RA.

Objective To compare SPECT/CT fusion imaging and MRI in the diagnosis of benign hip lesions. Methods Twenty-two patients suspected avascular necrosis of femoral head with hip discomfort, pain or action limited were analyzed retrospectively. All patients underwent radionuclide bone scan and MR examination within 5 days, and the diagnosis was proved with clinical follow-up. Results Eighteen necrosis of the femoral head and 4 hip arthritis including 1 patient with ankylosing spondylitis were found in 44 hip joints of 22 patients. MRI detected 17 femoral head necrosis and 4 hip arthritis, while SPECT/CT fusion image found out 18 femoral head necrosis and 4 hip arthritis. There was corresponding relationship in signs of hip lesions between MRI and SPECT/CT fusion imaging. Conclusion SPECT/CT fusion imaging and MRI has no markedly difference in the diagnosis of hip benign lesions, and is complementary to each other. SPECT/CT fusion image can distinguish the hip lesions from the femoral head lesions, and has a higher accuracy of diagnosing hip lesions than whole body bone scanning.

The aim of the study is to establish a platform to deliver therapeutic proteins into target cells through a polyarginine-based cell penetrating peptide. To facilitate the expression of therapeutic proteins, a pSUMO (Small Ubiquitin-like Modifier)-R9-EGFP (enhanced green fluorescence protein) prokaryotic expression vector was constructed. After induction, the fusion protein SUMO-R9-EGFP was efficiently expressed. To validate the cell penetrating ability of the fusion protein, HepG2 cells were incubated with the purified R9-EGFP or EGFP protein as control, internalization of the fluorescent proteins was examined by either flow cytometry or confocal microscopy. The result obtained by flow cytometry showed that the R9-EGFP fusion protein could efficiently penetrate into the HepG2 cells in a dose and time-dependent manner. In contrast, the fluorescence was barely detected in the HepG2 cells incubated with EGFP control. The fluorescence intensity of the R9-EGFP treated cells reached plateau phase after 1.5 h. The result obtained by confocal microscopy shows that R9-EGFP efficiently entered into the HepG2 cells and was exclusively located in the cytoplasm, whereas, no fluorescence was detected in the cells incubated with the EGFP control. The heparin inhibition experiment showed that heparin could inhibit penetrating effect of the R9-EGFP protein by about 50%, suggesting that the penetrating ability of the fusion protein is heparin-dependent. In summary, the study has established a platform to deliver therapeutic proteins into target cells through a polyarginine-based penetrating peptide.
Cell-Penetrating Peptides ; biosynthesis ; genetics ; pharmacology ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Hep G2 Cells ; Humans ; Peptides ; genetics ; metabolism ; Protein Transport ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology

The changes of Fas.FasL and Bcl-2 expression in thyrocytes of patients with Graves'disease were investigated before and 2 weeks after 131Ⅰ administration. The results showed that 131Ⅰ couhl induce thyrocytes to express the apoptotic protein Fas, FasL and the anti-apoptotic protein Bet-2 in patients with Graves'disease. A statistically significant correlation was found between the dose of 131Ⅰ and the expression levels of Fas and FasL but not Bet-2 ,suggesting that early onset of hypothyroid after 131Ⅰ administration may be due to the increased expression of Fas and FasL in thyrocytes.

Objective To investigate the effect of the eye-acupuncture therapy on serum TNF-α levels in rats with cerebral ischemia-reperfusion injury and the related mechanism. Methods Healthy SD rats were randomly divided into four groups: normal group, sham-operated control group, ischemia-reperfusion model group and eye-acupuncture group according to body weight. Sham-operated control group, ischemia-reperfusion model group and eye-acupuncture group were divided into the 3h group, the 24h group and the 72h group, a total of 10 groups (n=8). To establish the rat model of cerebral ischemia-reperfusion by suture method in ischemia-reperfusion model group and eye-acupuncture group. Eye-acupuncture was separately started immediately after reperfusion and at 30 min before sampling in the 3h eye-acupuncture group, besides, eye-acupuncture was separately taken every 12h in the 24h eye-acupuncture group and in the 72h eye-acupuncture group. The rats in normal group were not treated, those in sham-operated control group were inserted the fishing thread 1cm, and the others were identical with those in ischemia-reperfusion model group. At 3h, 24h, 72h after reperfusion, the neurophysical behaviours were accessed by ZeaLonga neurophysical impairment marks in ischemia-reperfusion model group and eye-acupuncture group. The method of ELISA was taken to detect the change of serum TNF-α levels in rats after the eye-acupuncture therapy. Results Compared with the ischemia-reperfusion model group, the neurologic impairment score of the eye-acupuncture group decreased obviously; The levels of serum TNF-αin ischemia-reperfusion model group at 3 h, 24 h, 72 h respectively were(76.803±18.325)pg/ml、(85.511±13.334)pg/ml、(86.831±9.232)pg/ml. The level of serum TNF-α in normal group was(24.304±6.511)pg/ml. The level of serum TNF-α in Sham-operated control group at 3 h, 24 h, 72 h respectively were(24.928±3.792)pg/ml,(27.533±5.362)pg/ml,(29.366±5.874)pg/ml. Ischemia-reperfusion model group compare with normal group and sham-operated control group, the difference were significant(P＜0.01). The levels of serum TNF-α in rats after the eye-acupuncture therapy at 3 h, 24 h, 72 h respectively were(40.185±3.335)pg/ml, (48.523±7.687)pg/ml, (51.611± 6.403)pg/ml. Compared with ischemia-reperfusion model group, the levels of serum TNF-α were strongly reduced(P＜0.01). Conclusion The eye-acupuncture therapy could play a role in improving cerebral ischemia-reperfusion injury evidently and the mechanism was related to its reducing serum TNF-α levels.

Objective To investigate the effect of arsenic trioxide (ATO) on the growth inhibition of bcr-abl mutant cell lines in vitro and to explore its potential mechanism. Methods The growth inhibition of ATO on bcr-abl wild type cell lines (K562, KBM5 and 32Dp210) and imatinib(IM)-resistant cell lines (K562R, KBM5R, 32Dp210T315I, 32Dp210Q252H, 32Dp210Y253H, 32Dp210M351T and 32Dp210E255K) were measured by trypan blue exclusion. Apoptosis was assayed by AnnexinV and PI staining. Glutathione (CSH) levels were detected by DTNB colorimetry of Glutathione Assay Kit. Results ATO inhibited cell growth in both bcr-abl wild type and IM-resistant mutant type cells in a dose dependent manner. ATO significantly inhibited growth of bcr-abl point mutant cells compared with the corresponding wild type cells, and the IC50 of ATO in mutant cells was lower than that in wild type, while the IC50 in no point mutant cells K562R was not different compared with that in wild type cells K562. The GSH levels in bcr-abl point mutant cells were lower than that in the corresponding wild type cells(P =0.00106-0.0358) , but that in K562 was quite similar with K562R cells(P = 0.315). After depletion of intracellular GSH by using BSO, the growth inhibition of ATO in both bcr-abl point mutant cells and wild type cells was significantly enhanced. Conclusion The growth inhibition of ATO on bcr-abl point mutant cells is remarkably more effective than that on wild type cells, which may be related with intracellular GSH. ATO would be a potential therapeutic select against CML with bcr-abl point mutation including the T315I mutation.

Insulin is the most common medicine used for diabetic patients, unfortunately, its effective time is short, even the long-acting insulin cannot obtain a satisfactory effect. Fibroblast growth factor (FGF)-21 is a recently discovered glucose mediator and expected to be a potential anti-diabetic drug that does not rely on insulin. In this study, db/db mice were used as the type 2 diabetic model to examine whether mFGF-21 has the long-term blood lowering effect on the animal model. The results showed that mFGF-21 could stably maintain the blood glucose at normal level for a long-term in a dose-dependent manner. Administration of mFGF-21 once a day with three doses (0.125, 0.25 and 0.5 mg x kg(-1)) could maintain blood glucose of the model animals at normal level for at least 24 h. Administration of mFGF-21 every two days with the same doses could maintain blood glucose of the model animals at normal level for at least 48 h, although it took longer time for blood glucose to reach to normal level depending on doses used (twenty injections for 0.125 mg x kg(-1) and 0.25 mg x kg(-1) doses, ten injections for 0.5 mg x kg(-1) dose). Surprisingly, the blood glucose of the treated model animals still maintained at normal level for 24 h after the experiment terminated. Glycosylated hemoglobin level of the animals treated with mFGF-21, which represented long-term glucose status, decreased significantly compared to the control group and the insulin group. The results suggest that FGF-21 has potential to become a long-acting and potent anti-diabetic drug.

Fibroblast growth factor 21 (FGF21) is a member of FGF family. It has been demonstrated that FGF21 is an independent, safe and effective regulator of blood glucose levels in vivo. In order to improve the activity of FGF21, we exchanged the beta10-beta12 domain of the human FGF21 with that of the mouse FGF21 to construct a novel FGF21 gene (named hmFGF21), and then subcloned hmFGF21 gene into the SUMO expression vector to create pSUMO-hmFGF21 and transformed it into E. coli Rosetta for expression of the fusion protein SUMO-hmFGF21. Both in vitro and in vivo glucose regulation activity of hmFGF21 was evaluated. The SDS-PAGE result showed that compared with wild-type hFGF21, the soluble expression of hmFGF21 increased about 2-fold. HmFGF21 was more potent in stimulation of glucose uptake in HepG2 cells in vitro. The results of anti-diabetic effect on db/db mice demonstrated that hmFGF21 had better efficacy on controlling the blood glucose of the db/db diabetic animals than wild-type hFGF21. These results suggest that the biological properties of FGF21 are significantly improved by optimization.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.