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OBJECTIVE To stud y the regulation mechanism of miRNA- 18a and miRNA-4802 on drug resistance of lymphoma cells via autophagy. METHODS Using human burkitt ’s lymphoma cell Daudi and human mantle cell lymphoma cell JeKo- 1 as the research objects ，adriamycin（ADR）and vincristine （VCR）as experimental drugs. After treatment of ADR and VCR ，relative cell viability was detected with CCK- 8 kit；the expression of apoptosis marker protein activated cleaved caspase- 9 and cleaved caspase-6 were detected by Western blot assay. The drug resistances of the two cells to ADR and VCR were investigated. The difference of autophagy activity between the two kinds of cells by expression detection of autophagy related proteins LC 3-Ⅱ and p62，autophagy flow experiment and transmission electron microscope observation. Fluorescence quantitative polymerase chain reaction was used to investigate the expression differences of miRNA- 18a and miRNA- 4802，ULK1 and ATG 7 mRNA in the two cells，and to detect the expression differences of ULK 1 and ATG 7 proteins. Taking JeKo- 1 cells as the research object ，the changes of autophagy activity and drug resistance were investigated after treatment with endogenous miRNAs （miRNA-18a mimics ， miRNA-4802 mimics）of two simulated organisms. RESULTS After ADR and VCR treatment ，compared with Daudi cells ，JeKo-1 cells had stronger drug resistance and autophagy activity. The expression of miRNA- 18a and miRNA- 4802 in JeKo- 1 cells were significantly lower than Daudi cells ，mRNA and protein expression of ULK 1 and ATG 7 were significantly higher than those of Daudi cells （P＜0.001）. After treatment of miRNA- 18a mimics and miRNA- 4802 mimics，the autophagy activities and drug resistances of JeKo- 1 cells were decreased significantly. CONCLUSIONS miRNA-18a and miRNA- 4802 can decrease drug resistances of lymphoma cells to ADR and VCR by reducing 2 the expression of autophagy-initiating genes ULK1 and ATG7， and inhibiting the autophagy activity of lymphoma cells.
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Blood glucose monitoring is an important part and means in the process of diabetes treatment and management. There is a high correlation between glucose concentration in interstitial fluid and glucose concentration in blood. Real-time monitoring of glucose concentration in interstitial fluid has important clinical significance. Continuous glucose monitoring (CGM) is an emerging glucose monitoring technology, which indirectly reflects the blood glucose level of the body through the glucose level in the interstitial fluid, providing continuous and comprehensive information and rules of blood glucose variation over a period of time. There are three main categories of CGM: minimally invasive implantation, non-invasive microtransparency and non-invasive technology. Noninvasive blood glucose monitoring technology is the future development direction, but accuracy and delay of blood glucose will be the biggest challenge to be overcome in clinical application.
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Objective To investigate the gender difference of the plasma lactic acid(LA) levels in type 2 diabetics with normal renal and hepatic function, and the effect of metformin on LA levels in the difference gender. Methods A total of 1 021 type 2 diabetic inpatients with normal renal and hepatic functions were collected,including metformin treatment group (213 males and 210 females) and metformin non-treatment group (299 males and 299 females). LA was measured with enzyme-electrode assay. Fasting plasma glucose ( FPG), creatinine ( Cr), and alanine aminotransferase ( ALT) levels were determined. Results LA level in metformin treatment group was significantly higher than that in metformin non-treatment group [ (1.32±0.53 vs 1.14±0.49) mmol/L,P<0.01],and 61 cases had hyperlactacidemia but no lactic acidosis was found. Spearman correlation analysis showed that LA level was positively associated with gender,metformin, and body mass index( BMI) apart from Cr and ALT( P<0.01). Multivariate logistic regression analysis showed that gender,Cr,ALT,and metformin were independent correlated factors of hyperlactacidemia. LA levels in females were higher than those of males in the whole group and two groups treated or not treated with metformin (all P<0. 05 ). LA levels in females were higher compared to male in Cr and ALT subgroups,as well as age subgroups,especially with age younger than 45 years old (P=0.021). Conclusions There is gender difference of lactate level in diabetic patients,and the effect of metformin on the plasma lactate levels of different gender is varied. The plasma LA level in females,especially those approaching menopause,are prone to hoist.
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ObjeclJve To definine the corresponding value to glycated albumin(GA)for a specific target of HbAlc,and to elvaluate the relationship between GA and HbA1c.Methods From Oct.2006 TO Apr.2009, 2 532 subjects were enrolled who accepted oral glucose tolerance test(OGtt)in out-patient department,including 898 with normal glucose regulation,695 with impaired glucose regulation,and 939 with newly-diagnosed diabetes.GA was measured with liquid enzymatic method.HbA1c was measured with high performance liquid chromatography method.The plasma glucose was measured at fasting,0.5 h,1 h,2 h,and 3h after glucose load.The correlation among GA,HbA1c and the other parameters monitored was analyzed.Results (1)The levels of HbA1c and GA in 2 532 subjects were(6.3±1.1)% and(17.9±4.5)%.The ratio of GA/HbA1c was 2.85±0.51.(2)HbAlc and GA were positively correlated with fasting,0.5 h,1 h,2 h and 3 h plasma glucose(r was in 0.567-0.776,atl P<0.01).(3)GA was significantly correlated with HbA1c(r=0.701,P<0.01).Linear regression analysis,using GA and HbA1c summarized by patient(n=2 532),produced a relationship of GA=2.871×HbA1c-0.112.The change in GA per increase of 1% HbA1c was 2.87%.When HbA1c level was 6.5%,the expected value of GA was 18.5%.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy with GA≤18.5% to predict HbA1c≤6.5% were 82.32%,72.49%,86.48%.65.73%,and 79.19%,respectively.When HbA1c level was 7.0%,the expected value of GA was 20.O%.When HbA1c level was 7.5%.the expected value of GA was 21.4%.Conclusions We initially establish the corresponding value to GA for a specific target of HbA1c and provide the basis for clinical application.
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Objective To study the relationship between plasma creatinine and lactic acid levels in type 2 diabetic patients with normal renal function, and the effect of mefformiu administration on plasma lactic acid. Methods Blood samples were collected from 723 type 2 diabetic inpatients(275 cases treated with mefformin as treatment group and 448 without mefformin as control group). Plasma lactic acid was measured with enzyme-electrode assay. The fasting plasma glucose, fasting insulin, creatinine (Cr) , alanine aminotransferase (ALT), and HbA1C levels were also determined. Results (1) The lactic acid level in treatment group was significantly higher than that in control group [(1.33±0.57 vs 1.17±0.47) mmol/L, P<0.01] and so was the incidence of hyperlactacidemia (9.45% vs 4.91%, P<0.01). No lactic acidosis was found in all patients. (2) The correlation analysis showed that Cr, blood urea nitrogen, ALT and body mass index (BMI) were positively correlated with lactic acid in control group, and the positive correlation between Cr and lactic acid still existed (r= 0.345, P<0.01) after adjustment for ALT and BMI. (3) After being divided by 20 μmol/L Cr in control group, lactic acid levels in subgroup increased with the Cr levels, especially when Cr was over 90 μmol/L. The Cr cutpoint for predicting lactatemia was 95.35 μmol/L. Conclusion It is safe to administrate metformin in type 2 diabetic patients with normal renal function, along with low risk of lactic acidemia. The incidence of lactic acidemia may increase when plasma Cr level reaches 95.35 μmol/L,
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Objective To explore the effect of all trans retinoic acid (ATRA) on the expression of CD106 and CD54 in human bone mesenchymal stem cells and cell growth curve in vitro. Methods The expression of CD54 and CD106 of human BM-MSC was detected by flow cytometry, and cell growth curve of human BM-MSC was tested by MTT assay after coculturing with 0.01, 0.1, 1.0 and 10.0 μmol/l ATRA, respectively. Results The expression of CD54 and CD106 is increased by 0.01, 0.1, 1.0 and 10.0 μmol/1 ATRA in vitro. Conclusion The expression of CD54, and CD106 of human BM-MSC was up-regulated by ATRA.
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Objective To evaluate the clinical significance of glycated albumin (GA), a parameter in reflecting recent glycemic control, in patients with impaired glucose regulation (IGR) and newly diagnosed diabetes mellitus. Methods From January to June 2007, 516 subjects who accepted oral glucose tolerance test (OGTT) in out-patient department were randomly enrolled, including 130 with normal glucose regulation (NGR), 154 with IGR and 232 with diabetes mellitus. The fasting plasma glucose (FPG), 0.5 h plasma glucose (PG), 1hPG, 2hPG, 3hPG after glucose loading, HbA1c and GA were measured in each subject. The correlation between GA and the other parameters were analyzed. Results There were significant differences in the values of GA among NGR, IGR and diabetes mellitus groups (all P < 0.01), but no difference in the values of HbA1c between NGR group and IGR group (P > 0.05). GA was positively correlated with HbA1c (r = 0.75, P < 0.01). Stepwise regression analysis showed that FPG, 2hPG and body mass index were the major independent contributing factors. Conclusion The combination of plasma glucose with GA measurement may be helpful in evaluating the status of glucose metabolism.