Objective To investigate whether repeated low-frequency transcranial magnetic stimulation (rTMS) can affect the expression of Kca1.1,Nav1.6,NMDAR1 and/or GAD65 protein in the pyramid layer of the CA3 region of the hippocampus.Methods Fifty rats were randomly divided into an experimental group and a sham group.The former was administered low-frequency rTMS on 14 consecutive days ; the latter were given sham stimulation for 14 days.After the protocols were completed,each group was sub-divided into 6 h,24 h,1 week,3 week and 6 week sub-groups.The rats of each sub-group were sacrificed at the corresponding time points and the expression of KCa1.1,Nav1.6,NMDAR1 and GAD65 in the CA3 region of the hippocampus was examined using immunohistochemical techniques.Results Compared with the sham group,KCa1.1-positive neuron densities increased significantly in the period 6 h to 3 weeks after rTMS.GAD65-positive neuron densities were also elevated significantly from 6 h to 3 weeks.NaV1.6-and NMDAR1-positive neuron densities decreased transiently at 6 h after the completion of the rTMS protocol.Conclusions These results show that low-frequency rTMS can upregulate the expression of KCa1.1 and GAD65,and that the effect lasts for at least 3 weeks.It transiently downregulates the expression of NaV 1.6 and NMDAR1 in the hippocampal CA3 region,at least in rats.These changes may be one of its anti-epileptic mechanisms.

Objective To investigate the effects of rhein on insulin sensitivity of diabetic rats induced by high fat feeding and low dose streptozotocin (STZ), and the possible mechanisms. Methods (1) Fifty-five Wistar rats were randomly divided into normal control group (NC,n=15) and diabetes group (DM, n=40). The NC rats were fed with regular chow and DM rats were fed with high fat diet. Five weeks later, the DM rats were injected with STZ 30 mg/kg once. The 30 diabetic rats were randomly divided into two subgroups, diabetic control group (DM-C) and diabetic group treated with rhein (DM-T). DM-T rats received intragastric administration of rhein and DM-C rats were given equal doses of solvent. All rats were sacrificed eleven weeks later, the blood sample was collected. The body weight, fasting blood glucose (FBG), HbA1C, triglycerides (TG), tolal cholesterol (TC), glycosylated serum protein (GSP) and Fasting insulin (FINS) concentrations were examined.The insulin sensitive index (ISI) and homeostasis model assessment for insulin resistance (HOMA-IR) werecalculated. (2) The PPART and GLUT-2 expression in hepatic tissue were detected by immunohistoehemistry and Western-blot. Results At the end of experiment the FBG [(22.57±3.23 vs 7.11±1.44) mmol/L,P<0.01],HbA1C[(12.49±1.96 vs 8.36±0.84)%, P<0.01], TG [(0.89±0.29 vs 0.58±0.17)nunoL/L,P<0.01],GSP [(57.29±4.14 vs 13.43±2.70)μmoL/L, P<0.01] and tumor necrosis factor-α [TNF-α,(1.365±0.133 vs 1.233±0.159) μg/L, P<0.05] and the liver weight index (0.032±0.004 vs 0.024±0.002, P<0.01) in DM-C rats were higher than those in NC rats. Besides, the ISI of DM-C rats decreased [In(ISI),-5.46±0.61 vs -4.81±0.75, P<0.05] and HOMA-IR elevated [In(HOMA-IR),2.34±0.64 vs 1.70±0.78,P<0.05]. The expression of PPARγ [11 131.7(5 723.1-18 979.4) vs 48 782.1(21 576.7-108 829.5), P<0.01] and GLUT-2 (0.98±0.35 vs 1.29±0.27, P<0.05) of DM-C rats decreased markedly compared with NC rats. Compared with DM-C rats, FBG [(15.94±3.16) mmol/L], HbA1C[(10.51±1.74)%], GSP[(47-31±6.09) μmol/L] in DM-T and the In (HOMA-IR), (1.86±0.30) rats decreased (P<0.05 or P<0.01), and In (ISI), of DM-T rats increased (-4.97±0.29, P<0.05). The expressions of PPARγ [35 156.3(24 554.3-86 660.9)] and GLUT-2 (1.55±0.55) of DM-T rats were up-regulated markedly compared with DM-C rats (P<0.05 or P<0.01). Conclusion Rhein decreased FBG, HbA1C and GSP, and improved the insulin sensitivity in diabetic rats, which might be related to the up-regulated expressions of PPARγ and GLUT-2 in hepatic tissue.

ObjectiveTo evaluate the safety and efficacy of 30 mg pioglitazone hydrochloride combined with sulphonyurea in the treatment of type 2 diabetic patients.MethodsA randomized, double blind, placebo-controlled, parallel group, multicenter study was performed.A total of 236 patients, who had fasting plasma glucose(FPG) 7.5-13.0 mmol/L and glycosylated hemoglobin A1c(HbA1 c) 7.0％ -12.0％,treated with stable dosage of a sulphonyurea for at least 30 days previously, were randomized to receive placebo or pioglitazone 30 mg once daily for 16 weeks.The sulphonyurea and dosage remained unchanged.ResultsThe patients who had been treated with pioglitazone 30 mg showed significant decrease than that in the placebo group on the average from baseline in FPG [(1.48 ±2.08) mmol/L vs (-0.17 ± 1.92)mmol/L, P＜0.05], and in HbAlc [(0.92 ±0.10)％ vs (0.28 ±0.11)％, P＜0.05].Since fasting plasma insulin (Flns) levels decreased (0.24 ±0.04) mU/L and (0.09 ±0.04) mU/L in the two groups.The homeostatic model assessment insulin resistant (HOMA-IR) decreased 1.42 ± 2.90 and 0.46 ± 3.53 in two groups.The triglyceride level was decreased 0.36 mmol/L and 0.14 mmol/L, and the HDL-C level increased 0.17 mmol/L and 0.05 mmol/L in two groups.There were significant differences in two groups (all P ＜ 0.05).ConclusionsThe 16-week clinical study demonstrated that pioglitazone hydrochloride with a dosage of 30mg daily, could significantly improve the blood glucose control and enhance the insulin sensitivity, lower triglyceride and raise HDL-C level as an additional therapy to a stable-dose sulphonyurea in Chinese type 2 diabetic patients previously poorly controlled by single sulphonyurea therapy, and furthermore had good safety and compliance.

Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.