Objective To study the role of gastric mitochondrial DNA cytochrome C oxidases (COX) subunit Ⅱ gene and its expression in diabetic gastric motility dysfunction. Methods Seventy Wister rats were randomly divided into 2 groups: diabetic group (STZ 60mg/Kg intraperitonealy) and control group. The changes in expressions of COX protein were assayed by Westernblot. Mitochondrial DNA COX mRNA was assayed with reverse-transcriptional polymerase chain reaction(RT-PCR). Cytochrome C oxidase activity was determined by ultraviolet spectrophotometer. Results Gastricelectric dysrythmia was more frequently delected in diabetic rats, and the COX activity in diabetic rats was 0.41?0.21/min, which was significantly lower than that in normal rats (0.78?0.37/min). The expression of gastrointestinal COX protein and COX gene in diabetic gastroparesis rats were markedly decreased compared with normal rats. Conclusion Cytochrome C oxidases activity was greatly reduced in diabetic rats. Diabetic gastroparesis was associated with down-regulation of the expression of gastrointestinal mtDNA encoding COX gene and protein. These changes might play a key role in pathogenesis of diabetic gastroparesis

Objective To investigate the relationship between mitochondrial membrane potential change and apoptosis of smooth muscle cells of the small intestine in diabetic rats. Methods Seventy Wistar rats were randomly divided into two groups: diabetic group(STZ60mg/kg intraperitonealy) and control group.The gastric empty time and intestinal transit were determined in diabetic rats 2 months after the reproduction of diabetes. Mitochondrial membrane potential in small intestinal smooth muscle cells was determined by the change in the intensity of labeling rhodamine 123 with lasor scanning confocal micrographs, and apoptosis index was assessed with the technique of terminal deoxynucleotidyl transferase mediated d-UTP nick end labeling(TUNEL) test and flow cytometry.The changes in expression of cytochrome C were determined by Western blotting. Results The mitochondrial membrane potential of small intestine smooth musele cells was significantly lowered in diabetic rats compared with normal rats. Apoptosis index in diabetic rats was significantly higher than that of normal as shown by TUNEL technic. Apoptosis rate in diabetic rats was 15%, and it was significantly higher than that of normal rat (P

Objective To study the change in cytosolic Ca 2+ in smooth muscle cells in gastric antrum of diabetic rat. Methods Rats were randomly divided into diabetic group and control group. Gastric empty time was determined 3 months after diabetes was reproduced in rats, the apoptosis rate of smooth muscle cells in the gastric antrum was assessed by flow cytometry, and the content of cytosolic Ca 2+ in smooth muscle cells was measured by laser scanning confocal microscopy. Results In diabetic rats, gastric emptying was significantly delayed. Compared the normal rats, the content of cytosolic Ca 2+ in smooth muscle cells from the antrum of diabetic rats was increased. The apoptosis rate of smooth muscle cells in the antrum of diabetic rats was 15%, and it was higher than that in normal rats. Conclusion With the increase in the content of cytosolic Ca 2+ in smooth muscle cells, smooth muscles were damaged and therefore their contraction was also impaired.

Objective To study the role of nitriergic nerves in the myenteric plexus of the gastric antrum in diabetic rats with motor disorder. Methods Rats were randomly divided into diabetic group and control group. Electrogastrogram was recorded, and the number of cholinergic nerves in the myenteric plexus of the gastric antrum was counted 3 months after reproducing diabetes in the model group. Results In the rats of diabetic group, gastro-electric dysrhythmia was observed more frequently, and the number of nitriergic cells in the myenteric nerves was significantly decreased compared with control group. Conclusion The changes in nitriergic nerves in the myenteric plexus of the gastric antrum might be one of the mechanisms of gastro-electric dysrhythmia and gastric motility disorders in diabetic rats.

Objective To study the effect of carbachol(CCH) on membrane potential of smooth muscle cells of gastric antrum of diabetic rats to verify the mechanism of gastric motility disturbance.Methods Fifty healthy Wistar rats of 2-month old,weighing 100-160 g,were divided into the control group(n=20) and diabetes mellitus group(n=30).Three months after the establishment of the rat model of diabetes by intraperitoneal injection of 60 mg/kg streptozotocin,gastric emptying time and gastric electrical activity were measured,and the resting membrane potentials of smooth muscle cells in antrum were measured by confocal laser scanning microscopy,then treated with carbachol of 10~(-9) mmol/L,10~(-8) mmol/L,10~(-7) mmol/L,the membrane potentials were measured.Results As compared with the normal rats,gastric emptying time in diabetic rats was significantly longer and abnormal gastric electric rhythm was significantly increased,the abnormal rhythm index(ARI) and the coefficient of variation(CV) of slow wave frequency in diabetic rats were significantly higher,but the resting membrane potentials remained unchanged and the sensitivity of CCH-induced membrane depolarization was increased.Conclusion The increase of sensitivity of CCH-induced membrane depolarization may be involved in the diabetes-induced gastric motor disorders.

Objective To clarify the changes of ultrastructure of interstitial cells of Cajal in the small intestine of diabetic rats. Methods Rats were randomly divided into diabetic group and control group. The rate of the small intestinal transit was measured and the tissues of the small intestine were observed by transmission electron microscopy at 3 months after the establishment of rat model of diabetics. Results In the diabetic rats, the rate of small intestinal transit was delayed as compared with that in the control group. The number of the gap junction of interstitial cells of Cajal in the small intestine of diabetic rats decreased significantly, and the rest structures were damaged. Damaged organelles and formation of vacuoles were also found. Conclusion The changes of ultrastructure of interstitial cells of Cajal in the small intestine may be one of the mechanisms resulting in slow rate of the small intestinal transit in diabetic rats.

Objective To observe the effect of acupuncture on ghrelin,estradiol (E2) and bone mineral density (BMD) in postmenopausal osteoporosis rats.Methods According to the random number table method,60 female Sprague-Dawley rats aged 3 months,were randomly divided into surgery group (40 rats) and sham group (20 rats).The osteoporosis model was established by bilateral ovariectomy.Three months after the operation,a significant decrease in BMD of lumbar vertebrae and femur of the model rats as measured by dual energy X-ray absorptionmetry against the sham group indicated successful establishment of the osteoporosis model.Then surgery group was randomly divided into a model subgroup,a acupuncture subgroup and an estrogen subgroup,with 10 rats in each subgroup.The acupuncture subgroup was treated with electroacupuncture,estrogen subgroup with subcutaneous injection of estradiol benzoate,sham group and model subgroup without any treatment.After 3 months of intervention all the rats were sacrificed,BMD of the lumbar vertebrae and femur was measured,ghrelin and E2 were determined.Results Serum ghrelin in acupuncture subgroup (399 pg/ml) and estrogen subgroup (276 pg/ml) were significantly lower (P ＜ 0.01) than that in model subgroup (546 pg/ml); serum E2 in acupuncture subgroup (128.02 pg/ml) and estrogen subgroup (182.89 pg/ml) increased significantly (P ＜ 0.05) than that in model subgroup (72.10 pg/ml) ;lumbar vertebrae BMD in acupuncture subgroup (0.212 g/cm2) and estrogen subgroup (0.231 g/cm2) increased significantly (P ＜ 0.05) than that in model subgroup (0.191 g/cm2),but in acupuncture subgroup the effect on improving the level of E2,ghrelin and lumbar vertebrae BMD was less than that in estrogen subgroup (P ＜ 0.05).Conclusions Acupuncture intervention can improve lumbar vertebrae BMD and serum E2 level of postmenopausal osteoporosis rat model,down regulate serum ghrelin level,but the overall effect of acupuncture is less than estrogen.

Background/Aims: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo. Results: TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage. Conclusions TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

Objective To investigate the association of distinct myositis specific autoantibodies (MSAs) with long-term survival of patients with polymyositis (PM) and dermatomyositis (DM).Methods We analyzed the clinical data and outcome of patients with PM and DM who were hospita-lized in the department of rheumatology of China-Japan Friendship hospital from 1994 to 2015,and evaluated the impact of MSAs on the prognosis of patients.Multivariate Cox regression analysis was used to identify the prognostic risk factors for PM/DM patients.Results A total of 383 PM/DM patients were followed up for 1-333 months.Cumulative survival and 10-year survival rate of all patients were 68.6％ and 76.2％,respectively.The survival rate of 80.4％ and 77.1％ at 3 and 5 years in patients with MSAs,which were lower than those of patients with-out MSAs,who had the survival rate of 90.1％ and 87.4％ at 3 and 5 years,respectively(x2=3.90 and 3.98,P＜0.05).There was significant difference for long-term survival in all MSAs positive groups (x2=40.654,P=0.000).Anti-MDA5 positive patients who had the 10-year survival rate of 28.7％ had the worst prognosis,while anti-HMGCR positive patients who had the l0-year survival rate of 100％ had the best outcome in all groups.Multivariate Cox regression analysis showed that independent risk factors associated with the long-term survival of patients were age of onset,complicated with malignancies,dysphagia,rapidly progress interstitial lung disease,antiMDA5 antibody positive,increased serum aspartate transferase and C reaction protein.Conclusion MSAs are strongly associated with the prognosis of patients with PM/DM.Patients with MSAs has worse 5-year overall survival than those without MSAs,which indicates that screening MSAs and aggressive treatment for PM/DM patients at very early stage of disease may improve the outcome.

Objective: To observe the efficacy and safety of CTD (cyclophosphamide, thalidomide, dexamethasone) and PCD (bortezomib, cyclophosphamide, dexamethasone) regimens in treatment of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A retrospective analysis was carried out on 88 cases of NDMM patients admitted to our hospital from July 2013 to January 2016, including 49 cases in CTD group and 39 cases in PCD group. The outcomes of two different regimens were analyzed, including response, prognosis, and adverse events. Results: The total overall remission rates (ORR, better than PR) of CTD and PCD were 65.3% (32/49) and 84.6% (33/39) , while very good partial response (VGPR) were 30.6% (15/49) and 53.8% (21/39) , and differences were statistically significant (P=0.041, P=0.028) . The median follow-up was 11.5 (3-33) months. The median progression-free survival (PFS) was (23.0±4.5) months in CTD groups, but it was not achieved in PCD group, with statistically significant differences (P=0.050) . Medial overall survival was not achieved in both two groups, without statistically significant difference (P=0.257) . There were statistical differences between patients with minor response (MR) and patients without MR in medium OS in CTD group (P=0.005) , and there were statistical difference between patients with VGPR and without VGPR in medium OS in CTD group (P=0.042) . Infection was a common adverse event in two groups. The incidences of peripheral neuropathy and herpes zoster were markedly higher in PCD group than CTD group, and the incidences of thrombus, palpation and rash, etc., were higher in CTD group. Conclusion Both CTD and PCD regimens were effective first-line induction chemotherapy choice for NDMM. PCD regimen is better than CTD in treatment power and deep remission.