Clinicopathological characteristics of metastatic ovarian tumor from digestive system / 中国医师进修杂志

Objective:To investigate the clinicopathological features of metastatic ovarian tumors from digestive system.Methods:The clinicopathological and follow-up data of 21 patients with metastatic ovarian tumor from digestive system were collected from April 2006 to January 2020 in the Maternity Hospital of Dalian Women and Children′s Medical Group. The pathological slides were reviewed, immunostained by EnVision method, and the clinicopathological features were summarized.Results:Twenty-one cases, aging from 26 to 66 years (average 41.5 years), were treated with chief complaint of abdominal pain, menstrual disorder or pelvic mass. The incidence of bilateral ovarian tumor was 81.0% (17/21), with a diameter of 0.2 to 20.0 cm. Most of tumors were solid and cystic, nodular or lobulated. Microscopically, tumor cells diffusely infiltrated ovarian stroma, accompanied with stromal proliferation and luteinization obviously. Metastatic gastric cancers were mainly signet-ring cell carcinomas, with cytokeratin 7 (CK7) positive, tail homeobox transcription factor 2 (CDX2) and cytokeratin 20 (CK20) partially positive, paired-box gene 8 (PAX8) and special AT-rich sequence binding protein 2 (SATB2) negative; metastatic colorectal cancers were mainly characterized by atypical glands, forming single cells or cribriform structure; metastatic appendix tumors were mostly low-grade tumor cells similar to ovarian borderline tumors and abundant extracellular mucinous, accompanied by peritoneal pseudomyxoma. The CK7 and PAX8 were negative, while the CK20, CDX2 and SATB2 were positive in patients with metastatic ovarian tumor from colorectal cancer and appendix tumor. The average follow-up time was 36 months, 18 patients relapsed within 5 years, 15 patients died; 3 patients were lost to follow-up.Conclusions:The ovarian metastatic tumors from digestive system are mostly bilateral, mainly solid and cystic. Microscopically, they show diffuse interstitial infiltration of tumor cells. The diagnosis should be combined with medical history, clinical symptoms, gross and histological features of tumor and immunohistochemistry, which should be mainly differentiated from primary mucinous ovarian tumor. The overall prognosis is poor.

Clinicopathological characteristics of primary ovarian mucinous adenocarcinoma / 中国医师进修杂志

Objective To investigate the clinicopathological characteristics of primary ovarian mucinous adenocarcinoma.Methods The clinical data of 28 patients with primary ovarian mucinous adenocarcinoma from April 2006 to December 2018 in Dalian Maternity Hospital Affiliated to Dalian Medical University were retrospectively analyzed.The pathological sections were reviewed,and the clinicopathological characteristics were analyzed by immunohistochemical staining.Results Among 28 patients,the average age of patients was 46.5 (22 to 64) years.Ten cases were found by health examination,15 cases showed lower abdominal discomfort,and 3 cases had irregular vaginal bleeding.Pelvic ultrasound examination showed heterogeneous internal echoes in adnexal region,and serum tumor marker levels did not significantly increase.The diameters of tumors were 8 to 32 cm,with an average of 16.5 cm.The unilateral ovarian tumor was in 26 cases,and bilateral ovarian tumor was in 2 cases.Most of tumors were solid-cystic with viscous liquid or jelly-like substance inside the cystic,accompanied with solid papillae or nodules.Microscopically,tumors were composed with gastrointestinal epithelium.Eighteen cases had borderline mucinous tumors with focal fusion infiltrating carcinoma;10 cases had fusion infiltrating carcinoma dominant,while there were 2 cases whose tumor exhibited focal invasive infiltration.Immunohistochemical result showed that the positive rates of cytokeratin (CK) 7,CK20 and tail-type homeobox gene (CDX) 2 were 100.0％ (28/28),71.4％ (20/28) and 53.6％ (15/28);the positive rates of paired box gene (PAX) 8 and special AT-rich sequence-binding protein (SATB) 2 were 14.3％ (4/28) and 10.7％ (3/28).According to the ovarian carcinoma stage standard of International Federation of Gynecology and Obstetrics (FIGO) 2014,Ⅰ stage was in 21 cases,Ⅱ stage in 4 cases,Ⅲ stage in 2 cases,and Ⅳ stage in 1 case.The patients were followed up for 3 to 120 months,with an average of 55 months.No recurrence or metastasis was in 17 cases (FIGO Ⅰ stage 16 cases,FIGO Ⅱ stage 1 case);recurrent within 2 years was in 5 cases (FIGO Ⅱ stage 2 cases,Ⅲ stage 2 cases,Ⅳ stage 1 case),of which 4 cases died within 5 years (FIGO Ⅱ stage 1 case,Ⅲ stage 2 cases,Ⅳ stage 1 case);lost to follow-up was in 6 cases (FIGO Ⅰ stage 5 cases,FIGO Ⅱ stage 1 case).Conclusions Primary ovarian mucinous adenocarcinoma is rare,and it has no specific clinical symptoms.It is mainly characterized by fusion infiltration.Immunohistochemical result shows that CK7 is always positive,the expressions of CK20 and CDX2 are different degree,and SATB2 and PAX-8 are mostly negative.Prognosis is closely related with FIGO stage,and the patients with FIGO Ⅰ stage have good prognoses,Ⅲ and Ⅳ stage have poor prognoses.It should be distinguished from ovarian metastatic mucinous tumor.

Metformin promotes autophagy in muscle cells exposed to palmitic acid through AMPK/SIRT3 pathway / 中华内分泌代谢杂志

Objective@#To investigate the effect of metformin on autophagy in muscle cells exposed to palmitic acid, and to explore its mechanism.@*Methods@#L6 rat myoblasts were incubated with palmitic acid at various concentrations(0.1, 0.2, 0.4, 0.6 mmol/L) and metformin(0.5, 1, 2, 5, 10 mmol/L) for 24 h. CCK8 method was used to detect the survival rate of muscle cells. After muscle cells were treated with palmitic acid and metformin for 24 h, mRNA and protein expressions of microtubule-associated protein11ight chain3(LC3Ⅱ), Beclin 1, p62, and silent mating type information regulation2 homolog-3(SIRT3) were detected by RT-PCR and Western blot, respectively. AMP-activated protein kinase(AMPK) phosphorylation level was detected by Western blot.@*Results@#Palmitic acid dose-dependently decreased the survival rate of muscle cells, which was attenuated by metformin at the concentration of 2 mmol/L. After muscle cells were incubated with 0.4 mmol/L palmitic acid and 2 mmol/L metformin for 24 h, palmitic acid significantly reduced the mRNA and protein expressions of LC3Ⅱ, Beclin1, and SIRT3 as well as phosphorylation level of AMPK(all P<0.05), and increased p62 mRNA and protein expressions(P<0.05). Those effects were all antagonized by metformin(all P<0.05).@*Conclusions@#Metformin treatment may promote the autophagy of muscle cells exposed to palmitic acid through AMPK/STRT3 pathway.

Clinicopathological characteristics of primary ovarian mucinous adenocarcinoma / 中国医师进修杂志

Objective@#To investigate the clinicopathological characteristics of primary ovarian mucinous adenocarcinoma.@*Methods@#The clinical data of 28 patients with primary ovarian mucinous adenocarcinoma from April 2006 to December 2018 in Dalian Maternity Hospital Affiliated to Dalian Medical University were retrospectively analyzed. The pathological sections were reviewed, and the clinicopathological characteristics were analyzed by immunohistochemical staining.@*Results@#Among 28 patients, the average age of patients was 46.5 (22 to 64) years. Ten cases were found by health examination, 15 cases showed lower abdominal discomfort, and 3 cases had irregular vaginal bleeding. Pelvic ultrasound examination showed heterogeneous internal echoes in adnexal region, and serum tumor marker levels did not significantly increase. The diameters of tumors were 8 to 32 cm, with an average of 16.5 cm. The unilateral ovarian tumor was in 26 cases, and bilateral ovarian tumor was in 2 cases. Most of tumors were solid-cystic with viscous liquid or jelly-like substance inside the cystic, accompanied with solid papillae or nodules. Microscopically, tumors were composed with gastrointestinal epithelium. Eighteen cases had borderline mucinous tumors with focal fusion infiltrating carcinoma; 10 cases had fusion infiltrating carcinoma dominant, while there were 2 cases whose tumor exhibited focal invasive infiltration. Immunohistochemical result showed that the positive rates of cytokeratin (CK) 7, CK20 and tail-type homeobox gene (CDX) 2 were 100.0% (28/28), 71.4% (20/28) and 53.6% (15/28); the positive rates of paired box gene (PAX) 8 and special AT-rich sequence-binding protein (SATB) 2 were 14.3%(4/28) and 10.7% (3/28). According to the ovarian carcinoma stage standard of International Federation of Gynecology and Obstetrics (FIGO) 2014, Ⅰ stage was in 21 cases, Ⅱstage in 4 cases, Ⅲ stage in 2 cases, and Ⅳ stage in 1 case. The patients were followed up for 3 to 120 months, with an average of 55 months. No recurrence or metastasis was in 17 cases (FIGO Ⅰ stage 16 cases, FIGO Ⅱ stage 1 case); recurrent within 2 years was in 5 cases (FIGO Ⅱ stage 2 cases, Ⅲ stage 2 cases, Ⅳ stage 1 case), of which 4 cases died within 5 years (FIGO Ⅱ stage 1 case, Ⅲ stage 2 cases, Ⅳ stage 1 case); lost to follow-up was in 6 cases (FIGO Ⅰ stage 5 cases, FIGO Ⅱ stage 1 case).@*Conclusions@#Primary ovarian mucinous adenocarcinoma is rare, and it has no specific clinical symptoms. It is mainly characterized by fusion infiltration. Immunohistochemical result shows that CK7 is always positive, the expressions of CK20 and CDX2 are different degree, and SATB2 and PAX-8 are mostly negative. Prognosis is closely related with FIGO stage, and the patients with FIGO Ⅰ stage have good prognoses, Ⅲ and Ⅳ stage have poor prognoses. It should be distinguished from ovarian metastatic mucinous tumor.

Metformin promotes autophagy in muscle cells exposed to palmitic acid through AMPK/SIRT3 pathway / 中华内分泌代谢杂志

Objective:To investigate the effect of metformin on autophagy in muscle cells exposed to palmitic acid, and to explore its mechanism.Methods:L6 rat myoblasts were incubated with palmitic acid at various concentrations(0.1, 0.2, 0.4, 0.6 mmol/L) and metformin(0.5, 1, 2, 5, 10 mmol/L) for 24 h. CCK8 method was used to detect the survival rate of muscle cells. After muscle cells were treated with palmitic acid and metformin for 24 h, mRNA and protein expressions of microtubule-associated protein11ight chain3(LC3Ⅱ), Beclin 1, p62, and silent mating type information regulation2 homolog-3(SIRT3) were detected by RT-PCR and Western blot, respectively. AMP-activated protein kinase(AMPK) phosphorylation level was detected by Western blot.Results:Palmitic acid dose-dependently decreased the survival rate of muscle cells, which was attenuated by metformin at the concentration of 2 mmol/L. After muscle cells were incubated with 0.4 mmol/L palmitic acid and 2 mmol/L metformin for 24 h, palmitic acid significantly reduced the mRNA and protein expressions of LC3Ⅱ, Beclin1, and SIRT3 as well as phosphorylation level of AMPK(all P<0.05), and increased p62 mRNA and protein expressions( P<0.05). Those effects were all antagonized by metformin(all P<0.05). Conclusions:Metformin treatment may promote the autophagy of muscle cells exposed to palmitic acid through AMPK/STRT3 pathway.

Mechanisms of peroxisome proliferator-activated receptor gamma coactivator 1α in high-fat diet-induced skeletal muscle mitochondrial dysfunction in rats / 中华老年医学杂志

Objective To investigate the role of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) in high-fat diet-induced insulin resistance (IR) and mitochondrial degeneration in skeletal muscle.Methods Wistar rats were randomly divided into a normal chow (NC)group (n =10) and a high-fat diet(HFD)group (n =10).After eight weeks,fasting plasma glucose(FBG) levels,fasting insulin(FINS) levels and glucose infusion rates (GIR) in each group were measured (n=3).Samples of rat skeletal muscle were harvested.L6 myoblasts were divided into a control group,a PA group (cells were cultured in palmitic acid),a pcDNA3 group (cells were transfected by the plasmid pcDNA3)and a pcDNA3-PGC1α group (cells were transfected by the PGC1α-overexpressiorn plasmid).Expression levels of PGC1α,nuclear respiratory factor 1 (NRF1),uncoupling protein 3 (UCP3),and cytochrome C oxidase 1 (COX1) in skeletal muscle and L6 myoblasts were measured by real-time PCR and Western blotting.Results Levels of FBG and insulin were higher and those of GIR were lower in the HFD group than in the NC group,(6.0±0.7)mmol/L vs.(5.0±0.4)mmol/L、(23.3±3.0)mU/L vs.(12.9±1.8)mU/L、(14.2±1.8)％ vs.(22.6±2.4)％ (t =-3.578,-6.679,6.265,respectively,P ＜ 0.05).Expression levels of PGC1α,NRF1,UCP3,and COX1 were down in skeletal muscle in the HFD group compared with those in the NC group(P ＜0.05).In L6 myoblasts cultured with palmitic acid,the expression of PGC1 α,NRF1,UCP3,and COX1 were down compared with their expression in the NC group (P ＜ 0.05).However,the altered expression of PGC1α,NRF1,UCP3,and COX1 was reversed by transfecting with PGC1α-overexpression plasmids (F =30.079,96.883,226.772,respectively,P ＜ 0.001).Conclusions High-fat diets can lead to insulin resistance and decreased expression of mitochondrial energy metabolism-related genes,which can be reversed by PGC1α.The decreased expression of PGC1α may mediate the high-fat diet-induced mitochondrial dysfunction and IR.

Application and clinical significance of Silva pattern system in invasive endocervical adenocarcinoma / 中华妇产科杂志

Objective To investigate the significance of Silva pattern system about clinical application in invasive endocervical adenocarcinoma. Methods Data obtained from the Maternity Affiliated Hospital of Dalian Medical University was analyzed, 78 endocervical adenocarcinoma cases were included from December, 2006 to August, 2017. The average age of patients was (45.1 ± 9.1) years old (ranged 27-71 years old). Clinical stage: stageⅠa 26 cases and Ⅰb 49 cases and stage Ⅱa 3 cases. All pathological slides were reviewed, stratified cases into pattern A, B and C according to Silva system criteria.Clinicopathological parameters of three Silva subgroups were analyzed, χ2 test was used to investigate the correlation of Silva system and clinicopathological parameters. Follow-up data were collected until Jan. 3rd, 2018. The median follow-up time was 41 months (ranged 5-90 months). Kruskal-Wallis H test and Fisher test were used to analyze prognoses among different Silva subgroups. Results (1) Silva A cases accounted for 38％(30/78) of all patients, 24 cases were stageⅠa, 6 cases were stageⅠb. The median tumor thickness was 2.1 mm (ranged 1.0-10.0 mm). No lymph vascular space invasion (LVSI) and perineural invasion (PNI) was detected, and all lymph node (LN) were negative for metastatic carcinoma. All patients were alive and had no evidence of recurrence. About 21％(16/78) cases were classified as Silva B, including 2 stageⅠa and 14 stage Ⅰb. The median tumor thickness was 5.2 mm (ranged 2.0-11.0 mm). Several patients had LVSI (4/16), LN metastasis (1/10) or PNI (1/16), but there was no recurrence or death. Thirty two (41％,32/78) cases were Silva C, including 29 stageⅠb and 3 stageⅡa. The median tumor thickness was 11.5 mm (ranged 4.0-21.0 mm). The incidence of LVSI (53％, 17/32), LN metastasis (31％, 8/26) or PNI (16％, 5/32) was significantly increased. There were two recurrent cases and one death cases. (2) Statistical data demonstrated that Silva pattern system was closely correlated with clinicopathological parameters , such as clinical stage (r=0.754, P=0.000), tumor depth (P=0.000) and LVSI (r=0.534, P=0.000). But there was no correlation between Silva system and LN metastasis or PNI (all P>0.05). (3) Silva subgroups demonstrated no significant difference in recurrence and death (P>0.05). Conclusions The application of Silva pattern system could effectively predict the prognosis of patients. It may be helpful to select reasonable operation before surgery and to realize individualized treatment of cervical adenocarcinoma.

Clinicopathological features of ovarian borderline seromucinous tumor / 中国医师进修杂志

Objective To investigate the clinicopathological features of ovarian borderline seromucinous tumor. Methods The clinical data of 22 ovarian borderline seromucinous tumor from April 2015 to March 2018 were retrospectively analyzed. The clinicopathological features were summarized by immunohistochemical staining with EnVision method. Results The age of patients was 23 to 66 years, with an average age of 39.2 years and a median age of 36 years. In the 22 patients, 14 patients were found by physical examination, 7 patients had abdominal discomfort or irregular vaginal bleeding, 4 patients had a history of dysmenorrheal, and 5 patients had cancer antigen 125 and/ or carcinoembryonic antigen elevation. Ultrasonography revealed mass in the adnexal region. The average diameter of these tumors was 7.2 cm. The tumors were cystic or cystic solid property and contained viscid or hemorrhagic fluid, with endogenous or exogenous papilla. Microscopically, these tumors showed complex papillary architecture and the larger papillae tended to have edematous stroma containing neutrophils. The epithelium lining the papillae was typically stratified and mostly composed of endocervical-type mucinous or serous epithelium, but endometrioid epithelium was not unusual. Eleven patients had endometriosis, and 2 cases occurred peritoneal or omental tumor implantation respectively. Immunohistochemistry showed that the estrogen receptor (ER), progesterone receptor (PR), paired box gene (PAX) 8 and cytokeratin (CK) 7 were positive in different degrees, and the CK20 and tail-type homeobox gene (CDX) 2 were negative in all patients. Twenty patients were International Federation of Gynecology and Obstetrics (FIGO)Ⅰstage without recurrence or metastasis in 3 to 36 months (average 13.6 months)′ follow-up. Conclusions Most patients with the ovarian borderline seromucinous tumor are young without specific clinical symptoms. Tumor is associated with endometriosis and maybe has characteristic histological changes. Attention should be paid to the differentiation from borderline serous and mucinous tumor before the final diagnosis. Most patients with ovarian borderline seromucinous tumor are FIGO Ⅰ stage and have the good prognosis. The clinical treatment is referred to the treatment of borderline endometrioid tumors.

Five cases of ovarian malignant tumor with thyroid component and literature review / 中国医师进修杂志

Objective To investigate the clinicopathological features of ovarian malignant tumor with thyroid components. Methods The clinical and pathological data of ovarian malignant tumor withthyroid component were collected from May 2006 to March 2018, including four cases of stroumal carcinoid and one case of metastatic thyroid follicular carcinoma, and the related literature was also reviewed. Results Ages of 5 cases ranged from 25 to 65 years old, and pelvic mass or abdominal discomfort was presented in physical examination. Tumors were unilateral, and mainly on the left side. The diameter of tumors was 5 to 13 cm with cyst or solid mainly. The strumal and carcinoid components were seen in strumal carcinoid. The insular and trabecular carcinoid were the common types of carcinoid. The synaptophysin (Syn) and chromogranin (CgA) were positive by immunohistochemistry. The patient with metastatic thyroid follicular carcinoma of ovary had a history of thyroid nodules for 13 years and the tumor grew rapidly in a short time. Under the microscope, dense thyroid follicles were arranged in papillary or diffuse distribution. Tumor cells were rich in eosinophilic cytoplasm and accompanied by follicular cell tumor-like hyperplasia. Conclusions Papillary tumor and strumal carcinoid are the most common primary malignant tumors of ovary with thyroid component, which both presented low malignancy and good prognosis. Ovarian metastasis from thyroid cancer is extremely rare and needs to be differentiated from primary ovarian thyroid cancer.

Application and clinical significance of human papilloma virus E6/E7 mRNA detection in cervical atypical glandular cells / 中国医师进修杂志

Objective To investigate the application and clinical significance of human papilloma virus (HPV) E6/E7 mRNA detection in cervical atypical glandular cells (AGC). Methods Four hundred and forty-five cervical AGC patients diagnosed by thin-layer liquid-based cytology in the Maternity Affiliated Hospital of Dalian Medical University from January 2014 to March 2018 were collected. Histological follow-up data and HPV E6/E7 mRNA detection results were analyzed, and histological differences in HPV E6/E7 mRNA positive and negative patients were compared. Results The histological result of 445 patients with cervical AGC showed that negative was in 306 cases (68.76%), and clinical significant lesion was in 129 cases (28.99%). In 445 patients with cervical AGC, HPV E6/E7 mRNA result was positive in 121 cases (27.19%), among whom the positive rate of HPV 16 and 18/45 type was 54.55% (66/121); HPV E6/E7 mRNA result was negative in 324 cases (72.81% ), including 13 non-cervical lesions. The negative rate of histological results in HPV E6/E7 mRNA negative patients was significantly higher than that in HPV E6/E7 mRNA positive patients: 91.05% (295/324) vs. 9.09% (11/121), and there was statistical difference (P＜0.01); the rates of adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesion (HSIL) and cervical adenocarcinoma of histological result in HPV E6/E7 mRNA positive patients were significantly higher than those in HPV E6/E7 mRNA negative patients: 40.50% (49/121) vs. 1.23% (4/324), 44.63% (54/121) vs. 1.23% (4/324), 3.31% (4/121) vs. 0.31% (1/324), and there were statistical differences (P＜0.01). The sensitivity of HPV E6/E7 mRNA in detecting clinical significant lesion of cervical AGC patients was 82.95% (107/129), the specificity was 95.57% (302/316), positive predictive value was 88.43% (107/121), and negative predictive value was 93.21% (302/324). Conclusions The histological result of cervical AGC shows that the amount of negative patients is significantly higher than clinical significant lesion. For cervical AGC patients with HPV E6/E7 mRNA negative results, conservative follow-up can be adopted after excluding extracervical lesions and fully assessing the risk of cervical lesions. However, the cervical AGC patients with HPV E6/E7 mRNA positive results need further examination to detect lesion and choose treatment earlier.

Protection effect of ATF-4 knockdown on fructose-induced steatosis in HepG2 cells / 实用医学杂志

Objective To investigate he intervention effect of knockdown of activating transcription factor 4(ATF-4)on fructose-induced lipid accumulation in liver cells. Methods HepG2 cells were divided into the control group(C),high fructose group(F),high-fructose+negative control group(F+NC)and high-fructose+ATF-4 siRNA group(F+ATF-4-). The mRNA level of gens of the upstream transcriptional factors and ERS markers was detected. The protein level of ACC,FAS and SCD-1 was also detected. Results Compared with group C,the mRNA expression of SREBP-1c,ChREBP,GRP78 and CHOP was increased(P < 0.01),while ATF-4 knock-down decreased the expression of the above genes(P < 0.01 ,respectively). Compared with group C ,the protein expression of ACC,FAS and SCD-1 was increased in group F(P<0.01,respectively). While ATF-4 knockdown decreased the protein expression of ACC ,FAS and SCD-1. Conclusions ATF-4 knockdown can improve the lipid steatosis induced by fructose through down-regulating lipid lipogenesis ,indicating ATF-4 possesses a regulatory effect on lipogenesis.

Effects of 5-aminoimidazole-4-carboxamide ribonucleotide on the palmitic acid-induced expression of mitochondrial function-related proteins in C2 C12 skeletal muscle cells / 中华老年医学杂志

Objective To investigate the effects of activated protein kinase(AMPK)agonists on the expression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1a),mitofusin 2 (Mfn2) and nuclear respiratory factor1 (NRF1)in the process of lipid-induced mitochondrial dysfunction of skeletal muscles.Methods The expression of PGC1α,Mfn2 and NRF1 in C2C12 skeletal muscle cells after intervention with palmitic acid was detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting.The effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on Mfn2 and NRF1 and,the expression of Mfn2 and NRF1 in C2C12 cells induced by a PGC1α activator and PGC1α-siRNA were assessed by Western blotting.Results Palmitic acid decreased the mRNA and protein expression of PGC1α,Mfn2 and NRF1 in C2C12 cells (P＜0.05).Additionally,AICAR,rosiglitazone and metformin up-regulated PGC1α expression,regardless of the presence of palmitic acid and,AICAR reversed lipid-induced PGC1α,Mfn2 and NRF1 attenuation in C2C12 cells.Furthermore,Mfn2 and NRF1 protein expression increased with PGC1α over-expression,and decreased with down-regulated PGC1α expression.Conclusions AICAR can relieve the adverse effects of palmitic acid on PGC1α,Mfn2 and NRF1 in skeletal muscle cells.Moreover,it appears that AICAR can up-regulate Mfn2 and NRF1 expression through activating PGC1α.

Relationship between thioredoxin-interacting protein and islet β-cell dysfunction in patients with impaired glucose tolerance and hypertriglyceridemia / 中国糖尿病杂志

Objective To evaluate the relationship between thioredoxin-interacting protein(TXNIP) and pancreaticβ-cell function in impaired glucose tolerance patients with and without hypertriglyceridemia. Methods A total of 267 subjects were enrolled in this study and divided into three groups:impaired glucose tolerance(IGT)group(n= 90),impaired glucose tolerance and hypertriglyceridemia(IGT +HTG)group(n=87)and normal glucose tolerance(NGT)group(n=90). The levels of plasma TXNIP were measured. Intravenous glucose tolerance test was performed to evaluate the first-phase insulin response(FPIR). HOMA forβ-cell function(HOMA-β)was calculated to evaluate basal pancreatic β-cell function. Results TXNIP was significantly higher in IGT group than in NGT group(P＜ 0.05). TXNIP was much higher in IGT+ HTG group than in IGT group (P＜0.05). HOMA-βand FPIR were decreased gradually from NGT,IGT to IGT + HTG(P＜0.05). Correlation analysis showed that HOMA-β and FPIR were negatively correlated with TXNIP(P＜ 0.05). Conclusion The level of TXNIP is increased in IGT,especially in IGT with hypertriglyceridemia. Basal and first-phase isletβ-cell function are all associated with TXNIP.

Mechanism of fatty liver induced by high-fructose-feeding in rats and intervention effect of fenofibrate / 实用医学杂志

Objective To observe the effect of fenofibrate intervention on high-fructose-feeding-induced liver steatosis in rats and explore the possible mechanism. Methods Male Wistar rats were randomly divided into control group ,high fructose group and fenofibrate group[fenofibrate intervention started after 8 weeks of high fructose feeding ,30 mg/(kg · d)]. Rats were sacrificed after 12-week of high fructose feeding. Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),free triglyceride(TG)and liver TG content were determined;protein levels of fatty acid synthase(FAS),endoplasmic reticulum stress mark-er Bip and autophagy markers such as Atg7,Beclin1,LC3 and the related pathway mTOR in liver tissues were de-tected. Results Compared with those in control group and fenofibrate group,serum AST,serum total cholesterol, blood free TG and hepatic TG were significantly increased in high-fructose group(P < 0.01). The protein expres-sion of Fas,Bip and mTOR were significantly increased in high-fructose group compared with those in control group and fenofibrate group;the protein expression of Atg7,beclin1 and LC3 were significantly decreased in high-fructose group compared with those in control group and fenofibrate group. Conclusions Long-term high-fructose-feeding induces fatty liver and liver cell injury ,and may affect ERS and autophagy. High-fructose-feeding-in-duced fatty liver may be improved by fenofibrate and its underlying mechanism might be associated with Fas,ERS and autophagy in liver.

Efficacy of Liraglutide in Type 2 Diabetes Patients Complicated with Obesity / 中国药师

Objective:To observe the hypoglycemic and weight loss effects of liraglutide in type 2 diabetes mellitus (T2DM) com-plicated with obesity, and explore new treatment strategies for T2DM complicated with obesity. Methods: Totally 38 T2DM patients complicated with obesity with dissatisfactory blood sugar control treated with oral hypoglycemic drugs or insulin were enrolled and divid-ed into group A ( overweight group, 28 kg·m-2 >BMI≥24 kg·m-2 , 18 cases) and group B ( obesity group, BMI≥28 kg·m-2 , 20 cases) according to the body mass index ( BMI) . Liraglutide was used in all the participants for 12 weeks. The height, weight, BMI,HbA1c, fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG), fasting insulin(FINS),2-hour postprandial in-sulin (2hPINS),fast-c peptide(FCP), 2-hour postprandial c-peptide(2hCP) and insulin resistance index (HOMA-IR), pancreaticβcell function index( HOMA-β) of the two groups were detected before and after the liraglutide treatment. Results:After the treatment with liraglutide, HbA1c, FPG, 2hPG, FCP,2hCP,HOMA-β,HOMA-IR were significantly decreased (P<0. 01) than before in the two groups, while there were no significant differences between the groups(P>0. 05). However, the body weight in group B was sig-nificantly lower than before (P<0. 01), while there were no significant change in group A(P>0. 05). Conclusion: Liraglutide can effectively control blood glucose level, ameliorate insulin resistance and obviously decrease the body weight in the T2DM patients com-plicated with obesity.

Looking for the ideal insulin regimens for Chinese T2DM patients——Clinical application and research advance of high-ratio premix insulin analogues / 中国糖尿病杂志

Postprandial hyperglycemia is one of the characteristics of glucose profiles in Chinese T2DM patients. High-ratio premix insulin analogues with advantages of excellent pharmacokinetic characteristics and flexible and convenient administration provide a comprehensive solution for Chinese T2DM patients to effectively control postprandial glucose and reduce blood glucose fluctuation. This paper is a literature review on its clinical evidence and experience.

Effect of dietary fat acids on incretin and islet function / 军事医学

Objective To explore the effect of dietary fat acids on incretin and islet function in healthy adults .Methods Before each test, healthy subjects received a 1-week pre-experiment eucaloric diet .Fifteen subjects consumed two meals containing different fat acids , including high saturated fat acid ( HSF) and high monounsaturated fat acid ( HMF) .On two separate occasions,they underwent a minimum of 1-week washout between meals .At 0,30,60,120,180 and 240 min following meal intake, the plasma concentrations of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(GLP-1) and serum concentrations of glucose, insulin, triglycerides ( TG) and free fatty acid ( FFA) were measured.Results Postprandial glucose did not increase significantly following HSF and HMF meals (P>0.05).Compared with HMF meal, significant increase in AUCins240min,AUCTG240min and AUCFFA240minwas observed following HSF meal (P0.05). AUCI/AUCG was significantly lower following HMF meal as compared with HSF meal (P<0.05).Conclusion This study demonstrates that the function of GIP ,GLP-1 andβcell is affected by the dietary fat acids in healthy adults .The HMF meal may stimulate GIP and GLP-1 secretion to a greater extent than HSF meal .

Effect of oxymatrine on lipid metabolism regulated genes in liver of fat-induced insulin resistance in ApoE -/-mice / 中国药理学通报

Aim To investigate the effect of oxymatrine on lipid metabolism regulated genes in liver in fat-in-duced insulin resistance in ApoE -/- mice.Methods Seventeen C57BL/6J male mice were selected in normal control group.Sixty-eight ApoE -/- mice with high fat diet for 1 6 weeks,were randomly divided into model group,oxymatrine low,middle and high dose groups.Then they were gavaged for 8 weeks.Body weight and general biochemical indicators were deter-mined in mice.The mRNA and protein expression lev-els of LPL,FAT/CD36,CPT1 ,UCP2,SREBP-1 c,FAS and ACC were examined by real-time PCR and West-ern blot in the liver.Results Compared with model group,oxymatrine reduced body weight(BW),fasting blood glucose (FBG),cholesterol (TC ),triglyceride (TG),free fatty acids(FFA),fasting plasma insulin (FINS)and insulin resistance index(HOMA-IR)(P <0.05),while improved glucose infusion rate (GIR). Oxymatrine down-regulated the mRNA and protein ex-pression of LPL,FAT/CD36,UCP2,SREBP-1 c,FAS and ACC(P <0.05),and up-regulated the mRNA and protein expression of CPT1 in varying degrees (P <0.05).Conclusion Oxymatrine can regulate the ex-pression of lipid metabolism regulated genes in liver and improve insulin resistance in ApoE -/- mice in-duced by high fat diet.

Construction of type 2 diabetes rat models of lower limb ischemia by feeding with high-fat diet / 中国组织工程研究

BACKGROUND:The method of ligating or resecting rat lower limb femoral or iliac artery has been widely used to make rat models of lower limb ischemia, but there have been no stable and efective methods used to establish diabetic models of chronic atherosclerotic occlusive diseases and to evaluate the ischemic status of hindlimbs of models. OBJECTIVE: To establish type 2 diabetes rat models of lower limb ischemia by feeding with high-fat diet and to evaluate them. METHODS:Twenty rats were randomly and evenly divided into diabetes group (n=10) and control group (n=10). Rats in the diabetes group were fed with high-fat diet for 6 months, and were intraperitonealy injected with streptozotocin (50 mg/kg) to induce diabetes. Rats in the control group were fed with normal diet for 6 months. Rats in these two groups were subjected to ligation of femoral artery to establish right lower limb ischemia models. RESULTS AND CONCLUSION:At the first day of modeling, color Doppler flow imaging and CT angiography showed obviously decreased blood flow suggesting the success of establishing ischemia model. At 7 and14 days after modeling, the blood flow of rats in these two groups showed a gradual recovery as detected by color Doppler flow imaging. At 28 days after modeling, blood flow of rats in the diabetes group was significantly slower than that in the control group (P < 0.05). CT angiography showed that at 28 days after modeling, only a smal amount of compensatory increase in blood flow of the blood vessels at the ligation position of proximal right lower limb femoral artery was seen in the diabetes group, while no obvious blow was observed in the distal part. Histopathologic and immunohistochemical staining showed that at 28 days after modeling, destroyed tissue structure and inflammatory cel infiltration were observed in the ischemic region and capilary density on the affected side was lower than that on the healthy side. The protein expression of vascular endothelial growth factor in the ischemic muscle tissue of rats in the diabetes group was significantly increased compared with that in the control group (P < 0.05). These results show that diabetic rat models of lower limb ischemia can be successfuly established by long term high-fat diet feeding and femoral artery ligation and they can be validated by CT angiography.

Research progress of activating transcription factor 4 in glucose and lipid metabolism / 中国糖尿病杂志

[Summary] Activating transcription factor 4 (ATF4) is an alkaline leucine zipper transcriptional factor ,which is involved in many physiological metabolism processes such as stress response ,inflammation and tumor growth. Moreover ,recent studies have shown that ATF4 also plays a key role in regulating lipid and glucose metabolism ,insulin secretion and insulin sensitivity ,which may related to pathways such as endoplasmic reticulum stress (ERS ) ,peroxisome proliferator‐activated receptor gamma coactivator (PGC1α) and target of rapamycin (TOR). This article summarized the recent research progress of ATF4 in regulating glucose and lipid metabolism.