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Objective:To investigate the effect of high glucose on the release of interleukin (IL)-1β and IL-18 in placental trophoblast by activating NLRP3 inflammasome.Methods:Gestational diabetes mellitus(GDM) placentas and control placentas were collected and the expression levels of NLRP3 and Caspase-1 were determined. Human placental trophoblast HTR-8/SVneo were cultured and divided into control group(5.5 mmol/L glucose), high glucose group(25 mmol/L glucose), DMSO+ high glucose group, and Ac-YVAD-cmk(NLRP3 inflammasome inhibitor)+ high glucose group. The expression levels of NLRP3 and Caspase-1 in cells as well as the contents of IL-1β and IL-18 in the medium were determined.Results:The expression levels of NLRP3 and Caspase-1 in GDM placenta were higher than those in control placenta( P<0.05) and positively correlated with homeostasis model assessment of insulin resistant index(HOMA-IR) and fasting insulin. The expression levels of NLRP3 and Caspase-1 in HTR-8/SVneo cells and the secretion levels of IL-1β and IL-18 in high glucose group were higher than those in control group( P<0.05). Ac-YVAD-cmk significantly suppressed high glucose-stimulated IL-1β and IL-18 secretion( P<0.05). Conclusion:High glucose promotes the release of IL-1β and IL-18 from placental trophoblast via activating NLRP3 inflammasome.
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ObjectiveTo establish the frozen section method of Ferula ferulaeoides， and to study the histochemical localization of volatile oil and coumarins in different organs of F. ferulaeoides. MethodThe roots， stems， petioles and leaves of F. ferulaeoides were used as materials to investigate the concentration of sucrose protectant， liquid nitrogen flash-freezing time， embedding conditions， section thickness， freezing temperature and time and post-treatment methods， the most suitable section conditions were screened by comparing the integrity， microscopic effect， elongation and clarity of frozen sections. Sudan Ⅳ staining method and fluorescence microscopy were used to locate the volatile oil and coumarins of F. ferulaeoides. ResultThe optimal conditions for frozen sections of the roots， stems， petioles and leaves of F. ferulaeoides were as follows：10%， 15% and 20% gradient sucrose as the protectant for roots， 10%， 20% and 30% gradient sucrose as the protectant for stems and petioles， 20%， 25% and 30% gradient sucrose as the protectant for leaves， glue-water （2∶1） as the embedding agent， quick-freeze in liquid nitrogen for 20 s， warmed up at -25 ℃ for 30 min， sliced at -20 ℃ with the thickness of 25 μm， rinsed with the same concentration of sucrose solution （gradient sucrose solution selected the last concentration）， and the slices placed on the ice pack for a period of time and stored at room temperature. Among them， the concentration of sucrose protectant was the most important factor. The results of histochemical localization showed that volatile oil and coumarins in four organs of F. ferulaeoides were mainly distributed in resin canal. ConclusionFrozen section of F. ferulaeoides is established for the first time with high rate of slicing and simplified steps， its volatile oil and coumarins are mainly accumulated in resin canal.
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Objective:To assess the implementation of injection-related risk management based on WeChat platform for type 2 diabetic patients with the insulin self-injection.Methods:A total of 124 diabetic patients, who would receive insulin therapy by self-injection at home after discharge from the PLA 903 hospital during April 2017 to July 2018, were divided into the control group( n=62)and the study group( n=62). All patients were given routine education on insulin injection during the hospitalization,while the study group( n=62)received additional video and text education based on WeChat platform after discharge. The skill of self-injection and the status of blood glucose control were evaluated in both groups 4 weeks and 8 weeks after discharge, respectively. Results:The insulin injection skill, including skin disinfection [36(58%) vs. 11(18%),χ 2=21.42, P<0.01], exhaust before injection [62(100%) vs. 51(82%),χ 2=12.07, P<0.01], stay 10s after injection [60 (97%) vs. 47(76%),χ 2=11.52, P<0.01], disposal of used needle[49(79%) vs. 18(29%),χ 2=31.20, P<0.01], rotation of injection site [48(77%) vs. 35(56%),χ 2=6.16, P=0.01], insulin storage [62(100%) vs. 57(92%),χ 2=5.21, P=0.02], and the ability of correctly dealing with hypoglycemia [52(84%) vs. 38(61%),χ 2=7.94, P=0.01] in the study group were significantly better than those in the control group after 4 weeks of injection-related risk management. The fasting plasma glucose [(6.41±0.76) vs.(7.19±0.81)mmol/L, t=5.61, P<0.01], glycosylated hemoglobin A1c [(6.71±0.64)% vs. (7.37±0.78)%, t=5.18, P<0.01], incidence of hypoglycemia [6(10%) vs. 15(24%),χ 2=4.64, P=0.03] in the study group were significantly lower than those in the control group after 12 weeks of the management. Conclusion:The risk management based on WeChat platform can improve insulin self-injection skill and the ability of dealing with hypoglycemia,also promote effective blood glucose control for diabetes patients.
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Objective:To explore the effect and mechanism of fentanyl on promoting the stemness of breast cancer cell.Methods:From January 2018 to October 2019, human breast cancer cell line BT549 was used as the in vitro research object. Breast cancer cell BT549 was pretreated with 0.01 and 0.10 μmol/L fentanyl. Sphere formation assay and colony formation assay were performed to investigate the role of fentanyl on breast cancer cell stemness. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA level of stemness-related transcription factors gender-determining area Y box protein 2 (Sox2), octamer binding transcription factor 4 (Oct4) and Nanog. Western blotting assay was performed to determine the level of Wnt3a/β-catenin pathway-related markers Wnt3a, phosphorylated glycogen synthase kinase-3β (p-GSK-3β), glycogenase kinase-3β (GSK-3β) and β-catenin. After down-regulating Wnt3a, western blotting assay and sphere formation assay were performed.Results:The sphere diameter, colony formation rate and the expression of Sox2 mRNA, Oct4 mRNA, Nanog mRNA, Wnt3a, p-GSK-3β, GSK-3β and β-catenin in 0.01 and 0.10 μmol/L fentanyl-treated breast cancer cell were significant higher than those in blank control: (131.22 ± 1.06) and (636.37 ± 0.02) μm vs. (72.68 ± 0.13) μm, (41.33 ± 0.03)% and (60.58 ± 1.08)% vs. (20.93 ± 0.15)%, 2.25 ± 0.20 and 3.82 ± 0.84 vs. 1.00, 1.87 ± 1.06 and 3.35 ± 0.04 vs. 1.00, 2.85 ± 0.03 and 4.36 ± 0.50 vs. 1.00, 1.82 ± 0.03 and 2.57 ± 0.42 vs. 1.00, 2.04 ± 0.13 and 2.81 ± 0.05 vs. 1.00, 1.62 ± 0.17 and 2.93 ± 0.06 vs. 1.00, 2.15 ± 0.02 and 3.54 ± 0.21 vs. 1.00, the indexes in 0.10 μmol/L fentanyl-treated breast cancer cell were significantly higher than those in 0.01 μmol/L fentanyl-treated breast cancer cell, and there were statistical differences ( P<0.01). After down-regulating Wnt3a, the expressions of p-GSK-3β, GSK-3β, β-catenin, Sox2, Oct4 and sphere diameter were significantly lower than those in blank control: 0.12 ± 0.05 vs. 1.00, 0.53 ± 0.06 vs. 1.00 and 0.24 ± 0.21 vs. 1.00, 0.28 ± 0.10 vs. 1.00 and 0.06 ± 0.01 vs. 1.00, (18.14 ± 0.30) μm vs. (74.32 ± 0.12) μm, and there were statistical differences ( P<0.01). Conclusions:Fentanyl promotes breast cancer cell stemness by Wnt3a/β-catenin signaling pathway.
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Eighty patients with hyperthyroidism treated in PLA 903 Hospital from February 2016 to May 2017 were randomly divided into two groups with 40 cases in each group.Patients in control group received routine outpatient education and those in study group received regular formatted mobile short message during follow-up in addition to routine education.The knowledge of disease,the compliance and satisfaction of treatment were assessed.After 12 weeks of follow-up,the TSH level was higher [0.430(0.050,2.806) vs.0.210(0.003,1.098) mU/L,Z=-8.07,P＜0.01],FT3 [(3.24± 1.18) vs.(4.18±2.07)ng/L,t=-2.49,P＜ 0.05] and FT4 levels [(12.43±6.82) vs.(19.58±19.06) ng/L,t=-2.26,P＜0.05] were lower in study group than those in control group.The scores of disease knowledge (6.12± 1.77 vs.5.25±1.79,t=4.67,P＜0.05),the Morisky scores of medication compliance (3.77±0.47 vs.3.37±0.73,t=8.22,P＜0.01),the rates of compliance for returning (85％ vs.65％,x2=4.27,P＜0.05) and the satisfaction rates with treatments (93％ vs.75％,x2=3.30,P＜0.05) in the study group were significantly higher than those in the control group.The score of disease knowledge in study group increased from 4.32± 1.55 before treatment to 6.12± 1.77 after 12 weeks of follow-up (t=22.65,P＜0.01).The results indicate that the health education plus regular formatted text message during follow-up can effectively improve the disease knowledge score,the compliance and satisfaction with treatment in patients with hyperthyroidism.
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Objective To explored the effects of fentanyl on cell proliferation of H1299 cells, Methods After treating H1299 cells with different concentrations of fentanyl (0.001, 0.010, 0.100, 1.000 μM) for 12, 24, 48, 72 h, cell viability was detected by CCK-8 assay; the rate of cell apoptosis was determined by DAPI staining; the expression levels of Bax, Bcl-2, p-AKT and AKT protein were measured by Western blotting; Caspase-3 activity was determined by Caspase-3 activity assay kit. Results Compared with the control group, fentanyl obviously inhibited the viability of H1299 cells in a dose and time dependent way. Moreover, treatment with different concentrations of fentanyl(0.001, 0.010, 0.100, 1.000 μM) for 12, 24, 48, 72 h, the apoptosis rate of H1299 cells were significantly increased, The level of Bcl-2 protein reduced the level of Bax protein, and the activity of Caspase-3 in H1299 cells were increased after treatment with fentanyl (0.010, 0.100, 1.000 μM) for 48 h, Furthermore, fentanyl markedly inhibited p-AKT/AKT activity of H1299 cells. Conclusions Fentanyl can inhibit cell proliferation and promote cell apoptosis of human lung cancer, and its mechanism may be related to inhibition of AKT activation ,
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The clinical data of 96 patients with type 2 diabetes mellitus (T2DM) treated in Department of endocrinology of our hospital from January 2016 to December 2017 were retrospectively analyzed. All patients had been treated with metformin ≥1 000 mg combined with sulfonylureas for>12 weeks and their glycosylated hemoglobin (HbA1c) was>7.5%. On the basis of the original scheme, 57 patients received oral sitagliptin (100 mg q.d, sitagliptin group) and 39 patients received insulin glargine injection (insulin group) for 26 weeks. The blood lipid, liver and kidney function were examined before and after treatment. The abdominal visceral fat area (VFA) was measured by CT scan. Results showed that the fasting plasma glucose (FPG) , 2-hour postprandial blood glucose (2 hPG) and HbA1c were significantly lower than baseline levels in both groups(P<0.05). The decrease of VFA in sitagliptin and insulin groups was by 9.6 (1.4,19.6)cm2 and by 8.3(-2.2,26.8) cm2, respectively; there was significant difference in variation of VFA before and after treatment between the two groups (P<0.05). There was no significant difference in blood pressure, liver function (ALT, AST) and estimated glomerular filtration rate (eGFR) before and after treatment in the sitagliptin group (P>0.05). Additional sitagliptin administration can effectively and safely reduce HbA1c and decrease the abdominal visceral fat content in T2DM patients who failed to metformin and sulfonylureas combined therapy.
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Objective To study the effect of hydrogen sulfide on the production of soluble fms-like tyrosine kinase 1 (sFlt-1) through a distintegrin and metalloproteinase 17 (ADAM17) in adipocytes. Methods 3T3-L1 cells were cultured and induced to differentiate into adipocytes, then treated with different doses of sodium hydrogen sulfide (NaHS), L-cysteine or transfected with cystathionine-γ-lyase ( CSE) siRNA, ADAM17 siRNA or treated with ADAM17 inhibitor, monoclonal antibody. 24 hours after treatment, the expression of ADAM17, CSE, and the production of sFlt-1 were determined. Results After the treatment of 10, 25, 50 nmol/L NaHS or 0. 5, 1. 0, 2. 0 μmol/L L-cysteine, the expression of ADAM17 and the production of sFlt-1 in adipocytes were significantly decreased, the higher dose of L-cysteine and sFlt-1, the lower expression of ADAM17 and the production of sFlt-1; the effect of 2.0 μmol/L L-cysteine decreasing the expression of ADAM17 and the production of sFlt-1 were reversed by transfection of CSE siRNA; after the transfection of ADAM17 siRNA and treatment of ADAM17 inhibitor or monoclonal antibody, the production of sFlt-1 in adipocytes were significantly decreased. Conclusion Hydrogen sulfide can reduce the production of sFlt-1 in adipocytes by downregulating the expression of ADAM17.
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BACKGROUND@#Epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. The incidence of malignant pericardial effusion (MPCE) in EGFR-mutant NSCLC patients is high. However, there are few researches on the treatmentof this type of patients.@*METHODS@#We collected data on clinical characteristics and treatment of advanced NSCLC patients who harboring EGFR mutants and MPCE between January 2010 and December 2016. The treatments were divided into three groups: oral gefitinib combined with pericardial perfusion of hydroxycamptotheci (HCPT) group (gefitinib/HCPT); intravenous chemotherapy combined with pericardial perfusion of HCPT group (chemotherapy/HCPT) and gefitinib monotherapy group. And we retrospectively analyzed patients' outcomes in three groups.@*RESULTS@#In 273 advanced NSCLC patients with EGFR mutations, 29 cases had pericardial effusion, among which 6 patients with small amount of pericardial effusion were excluded, and 23 patients were analyzed. Median pericardium progression free survival (PFS) was 247 days. PFS for gefitinib/HCPT group (460 days) was superior to PFS for chemotherapy/HCPT group (94 days, P=0.008) and gefitinib monotherapy group (131 days, P=0.032). As for the efficacy of primary pulmonary lesions, the efficacy in gefitinib/ HCPT group was superior to chemotherapy/HCPT group [objective response rate (ORR): 33.3% vs 12.5%; disease control rate (DCR): 86.7% vs 62.5%]. There is no difference of ORR and DCR between gefitinib/HCPT group and gefitinib monotherapy group. No obvious adverse reaction was observed in all three groups.@*CONCLUSIONS@#First-line gefitinib therapy combined with pericardial perfusion of HCPT can improve pericardium PFS for advanced NSCLC patients who harboring EGFR mutants andmalignantpericardial effusion. This finding should be confirmed further through multicenter, prospective clinical trials with large sample size.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Metabolism , Pathology , Disease-Free Survival , ErbB Receptors , Metabolism , Gefitinib , Lung Neoplasms , Drug Therapy , Metabolism , Pathology , Perfusion , Pericardial Effusion , Pericardium , Quinazolines , Therapeutic Uses , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To investigate abdominal visceral fat area and its relationship with insulin resistance in male patients with type 2 diabetes and normal body mass index (BMI).Methods Seven male patients with type 2 diabetes and normal BMI were divided into two groups according to the abdominal visceral fat area (VFA) measured by CT:visceral obesity group (VFA ≥ 100 cm2) and non-visceral obesity group.Indicators of glucose and lipids metabolism were measured in two groups.Results Among 70 patients 50 (71％) had visceral obesity.In 59 patients who had normal BMI and normal waist circumference (≤90 cm),41 presented visceral obesity (69％).Compared with non-visceral obesity group,the waist circumference,homeostasis model assessment of insulin resistance (HOMA-IR),triglyceride,and VFA were significantly higher in visceral obesity group [(86.4 ± 5.6) vs.(81.2 ± 4.8) cm,t =-2.980,P ＜ 0.01;2.83±2.31 vs.2.01±1.30,t=-2.025,P＜0.05;1.93(1.26-2.79) vs.1.11(0.75-1.46) mmol/L,Z=-3.777,P＜0.01;(143.6 ±31.8)vs.(73.7 ±17.3)cm2,t =-11.456,P＜0.01].Fasting insulin,fasting plasma glucose and glycosylated hemoglobin tended higher in visceral obesity group but not significantly (P ＞ 0.05).Multiple linear regression analysis showed that after adjustment for age and body mass index,abdominal VFA was positively correlated with HOMA-IR (r =0.240,P ＜ 0.05).Conclusion Male type 2 diabetic patients have a high rate of visceral obesity even when their body mass index and waist circumference are normal.Abdominal visceral fat area is closely associated with insulin resistance.
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OBJECTIVE:To observe the efficacy and safety of metformin in the treatment of type 2 diabetes(T2DM) with non-alcoholic fatty liver disease(NAFLD). METHODS:106 patients with T2DM with NAFLD were randomly divided into control group and observation group. Control group was received health education about T2DM with NAFLD and living intervention(diabe-tes diet and physical therapy);observation group was additionally given Metformin tablet 0.5 g,orally,3 times a day. The treat-ment course for both groups was 12 weeks. Clinical efficacy,and liver fat content,BMI,FPG,IR,TG,TC,LDL-C,HDL-C,HbA1c before and after treatment,and incidence of adverse reactions in 2 groups were observed. RESULTS:After treatment,liver fat con-tent and related index in 2 groups were significantly better than before(except HOMA-IR in control group),and observaton group was better than control group,the differences were statistically significant(P<0.05). The total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P<0.05). CONCLUSIONS:Based on the conventional treatment,metformin has good efficacy and safety in the treatment of T2DM with NAFLD.
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Objective To investigate the prevalence of overweight,obesity and related metabolic diseases among male public institution office workers in health check-up.Methods Total 1 018 male public institution office workers aged 23-60 underwent annual health check-up at our hospital in 2012.The data including blood pressure,waist circumference,height,body weight,serum glucose,plasma lipids and serum uric acid were analyzed.According to body mass index (BMI),the subjects were classified as:underweight(BMI ＜ 18.5 kg/m2),normal weight (18.5 kg/m2 ≤ BMI ＜ 24 kg/m2),overweight (24 kg/m2 ≤ BMI ＜ 28 kg/m2) and obesity(BMI≥28 kg/m2).Results The prevalence of overweight,obesity,central obesity and metabolic syndrome (MS) were 40.9％ (416/1 018),7.9％ (80/1 018),53.0％ (540/1 018),and 11.2％ (114/1 018),respectively.There were significant differences in fasting blood glucose (FPG),TC,TG,uric acid(UA),systolic blood pressure(SBP) and diastolic blood pressure(DBP) levels among different groups (F =4.82,12.09,40.55,6.19,28.97 and 49.29,respectively,all P ＜0.01).The prevalence rate of hypertension in underweight,normal,overweight and obesity groups was 0,11.8％,27.4％ and 37.5％,respectively; that of diabetes was 0,1.6％,5.5％ and 10.0％,respectively; that of hyperlipidemia was 40.0％,47.2％,66.3％ and 71.2％,respectively; that of hyperuricemia was 0,5.0％,13.5％ and 13.8％,respectively,which showed that with the increasing of BMI,the prevalence rates of related metabolic diseases were increased(x2 =55.97,9.65,43.32 and 24.08,all P ＜0.01).And the co-morbidity rate with ≥3 diseases in 4 BMI groups were 0(0/20),1.4％ (7/502),5.8％ (24/416) and 13.8％ (11/80),respectively (x2 =31.90,P ＜ 0.01).Conclusion Obesity and overweight are correlated with metabolic disorders and the obese subjects are at high risk for cardiovascular diseases.
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Objective To investigate the association of serum visfatin and free fatty acid (FFA) with insulin resistance in type 2 diabetes mellitus (T2DM).Methods One hundred and nineteen patients with T2DM and 65 health subjects with normal glucose tolerance (NGT) were enrolled in the study.TheT2DM patients were further classified as insulin resistant (HOMA-IR ＞ 2.8 mU/L,T2DM-IR group,n =61) and non-insulin resistant (HOMA-IR≤2.8 mU/L,T2DM-NIR group,n =58).Serum visfatin,free fatty acid and related clinical variables were measured,and HOMA-IR was calculated.Results The serum levels of visfatin and FFA in T2DM patients were significantly higher than those in healthy controls [(4.7 ±2.5) vs.(1.7±0.9) ng/L,t=-11.831,P＜0.01; (1.65±0.69) vs.(0.61 ±0.21) mmol/L,t=-9.239,P ＜0.01].The serum levels of visfatin and FFA in T2DM-IR group were significantly higher than those in T2DM-NIR group [(6.3±2.3) vs.(3.0±1.4) ng/L,P＜0.01; (2.16±0.45) vs.(1.12± 0.46) mmol/L,P ＜0.01].Multiple regression analysis showed that FFA,fasting insulin level and waist/ hip ratio (WHR) were independent risk factors of serum visfatin level (r =0.564,0.267 and 0.188 respectively,all P ＜ 0.05).Conclusion Serum levels of visfatin and FFA are increased in T2DM,and they are closely associated with insulin resistance.
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Objective To investigate the association of serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1),soluble vascular cell adhesion molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hs-CRP) with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus (T2DM).Methods One hundred and thirty T2DM patients admitted from October 2011 to October 2012,and 30 age/sex-matched healthy subjects were enrolled in the study.The serum levels of sICAM-1,sVCAM-1,hs-CRP and other clinical parameters were measured; the peripheral blood vessels of lower limbs were examined with color Doppler ultrasonography.Based on the extent of angiopathy of lower limbs T2DM patients were classified as normal vascular group (n =26),mild angiopathy group (n =45),moderate/severe angiopathy group (n =59).Results The serum levels of sICAM-1 and sVCAM-1 in moderate/ severe angiopathy group of T2DM patients were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:4.15-8.93,all P ＜0.05) ; the serum levels of hs-CRP in moderate/severe angiopathy group were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:2.18-4.27,all P ＜ 0.05).The serum sICAM-1 level was positively correlated with total cholesterol (TC),low density lipoprotein cholesterol (LDL-C) and sVCAM-1.The serum sVCAM-1 level was positively correlated with course of disease,systolic blood pressure and CRP.Conclusions Serum levels of sICAM-1,sVCAM-1 and hs-CRP are correlated with the extent of angiopathy of lower limbs in T2DM patients,and the elevated sICAM-1 ; sVCAM-1 and hs-CRP levels are also associated with hyper blood pressure,dislipidemia and chronic inflammation.