Objective To explore the possible anti-inflammatory mechanism of intensive insulin therapy （IIT） by studying the effect of IIT on the levels of TNF-α, IL-6, C-reactive protein （CRP） and APACHE Ⅱ score in biliary pyemia. Methods Twenty eight patients with biliary pyemia who were admitted by our department and given an operation within 24 h form Jan. 2005 to Dec. 2008 were randomly divided into two groups by using random number table numbers: one group treated with IIT （IIT group, n=14） and another group treated with routine insulin therapy （RIT group, n=14）. The inflammatory factors, such as TNF-α, IL-6 and CRP were detected dynamically and the APACHEⅡ score was calculated. ResultsThe level of CRP and APACHEⅡ score on day 5 and 7 and the levels of TNF-α and IL-6 on day 3, 5 and 7 after operation in IIT group were significantly lower than those in RIT group （P＜0.05, P＜0.0１）. Compared with preoperative levels, the IL-6 and APACHEⅡ score in IIT group commenced to decrease on day 3 after operation （P＜0.05）, that was earlier than control group. Conclusion The treatment with IIT can suppress the composition of TNF-α, IL-6 and CRP, protect impaired hepatic cells, and reduce APACHEⅡ score, the degree of systemic inflammation and incidence of MODS.
Purpose To investigate the status of proliferation and activation of vascular endothelial cells in preretinal neovascular membranes from patients with insulin dependent diabetetes mellitus(IDDM)by means of immunohistochemical techniques. Methods Status of vascular endothelial cells in 18 preretinal neovascular membranes from 18 patients with IDDM was studied by double-immunofluorescence technique and the alkaline phosphataes-anti-alkaline phosphatase(APAAP)technique and compared the findings with the main clinical features of the patients. Results Of 18 vascularized membranes,16(88.9%)contained proliferating endothelial cells (positive for proliferating vascular endothelial cell marker EN 7/44) and 14 (77.8%) were positive for endothelial cell activation marker anti-VCAM-1;furthermore,by using a double staining technique,we found that in 14 of the 16 cases(87.5%) the proliferating vascular endothelial cells were activated (expressing VCAM-1). Conclusion The proliferation and activation of the vascular endothelial cells of the newly formed vessels in preretinal neovascular membranes suggests the significance of the vascular endothelial cells in the pathophysiology and the progress of proliferative diabetic retinopathy. (Chin J Ocul Fundus Dis,1998,14:141-143)
Exercise is vital for diabetics to improve their blood glucose level. However, the quantitative relationship between exercise modes (including types, intensity, time, etc.) and the blood glucose is still not clear. In order to answer these questions, this paper established a blood glucose metabolic model based on ordinary differential equation method. Furthermore, a silico method was adopted to study the effects of different aerobic exercise intensities (light, moderate and vigorous) on blood glucose and optimal strategies of insulin infusion for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Additionally, the universality of proposed model and insulin infusion strategies was verified based on 1 000 virtual diabetes patients’ simulation. The experimental results showed that: (1) Vigorous-intensity aerobic exercise may result in hypoglycemia (< 3.89 mmol/L), which was so harmful to health that diabetics should avoid. Compared with moderate-intensity exercise, the light-intensity aerobic exercise intuitively lowered blood glucose slowly and caused a relative long high-blood-glucose (> 6.11 mmol/L) period, however, its overall blood glucose risk index (BGRI) was lower. (2) Insulin dosage of the optimized strategies decreased by 50% and 84% for T1DM and T2DM when they did moderate intensity exercise. As for light intensity exercise, the dosage of insulin was almost the same as they didn’t do exercise, but BGRI decreased significantly. (3) The simulations of 1 000 virtual diabetic patients manifested that the proposed model and the insulin infusion strategies had good universality. The results of this study can not only help to improve the quantitative understanding about the effects of aerobic exercise on blood glucose of diabetic patients, but also contribute to the regulation and management of blood glucose in exercise mode.
ObjectiveTo compare the efficacy of sitagliptin plus glargine insulin versus repaglinide plus glargine insulin in the treatment of Type-2 diabetes mellitus (T2DM). MethodsA total of 140 T2DM patients who were inadequately controlled by oral anti-diabetic agents from January 2011 to December 2012 were divided into sitagliptin plus glargine insulin group (observation group) or repaglinide plus glargine insulin group (control group). The duration of treatment was 12 weeks. Fasting blood glucose (FBG), 2h plasma glucose (2hPG), glycated haemoglobin (HbA1c), body max index (BMI) and dose of insulin as well as hypoglycemia events were recorded and analyzed. ResultsAfter treatment, FBG, 2hPG, and HbA1c were significantly decreased in both groups (P<0.05). HbA1c targeting rate was 88.3% in the observation group and 87.8% in the control group. Compared with the control group, the observation group used 12.1% less dosage of insulin, and had decreased BMI and low incidence of hypoglycemia. ConclusionSitagliptin plus glargine insulin can effectively control blood glucose and body weight with low incidence of hypoglycemia and much less insulin dosage under the same HbA1c targeting rate. Sitagliptin plus glargine insulin is a good combination therapy for the treatment of T2DM.
Objective To establish a stable colorectal cancer model in liver specific insulin-like growth factor (IGF)-1 deficient (LID) mice and examine the potential relationship between IGF-1 level and risk of mice constitutional colorectal cancer. Methods ①Establishment of a colorectal cancer model: The LID mice, in which IGF-1 level in circulation was 25% of BALB/c mice. Induction of colorectal cancer was achieved by using the 1,1 Dimethylhydrazine (DMH) with hypodermic injection at transverse part. ②Eighty fresh samples of cancer tissues and adjacent tissues were obtained from LID mice (experimental group) and BALB/c mice (control group). The expression of IGF-1 was studied by immunohistochemical assay (SP method). Results ①Weight loss occurred in both experimental group and control group after injection. Compared with the body weight before injection on 18 weeks and 24 weeks in each group, there were significant differences after injection at the same phase in each group (P＜0.05). ②The results of IGF-1 expression in cancer tissues and adjacent tissues: IGF-1 got a diffuse distribution in cancer cell cytoplasm. The positive expressions of IGF-1 in the cancer tissues and their adjacent cancer tissues were 6/7, 2/7 and 13/16, 7/16 respectively in experimental group and control group. There were significant differences between the cancer tissues and adjacent tissues inside both groups (P＜0.05). There were no significant differences inside both of cancer tissues and adjacent tissues respectively between experimental group and control group (Pgt;0.05). Conclusion In the established colorectal cancer model by DMH, IGF-1 plays an important role in the development and progression of colorectal cancer.
Objective To evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients. Methods Between January 2020 and October 2021, the critically ill patients with stress hyperglycemia in the Emergency Intensive Care Unit of the Fourth People’s Hospital of Langfang were randomly assigned into a trial group or a control group. The trial group adopted hyperinsulinemic normoglycemia therapy, while the control group adopted conventional glucose control therapy. The mean and variability (standard deviation) of blood glucose, incidences of severe hypoglycemia and abnormal hyperglycemia, as well as the percentage of blood glucose values within the target range were compared between the two groups, to evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients from the perspective of safety and effectiveness. The non-normally distributed measurement data were presented as median (lower quartile, upper quartile). Results A total of eighty patients were included, with forty cases in each group. The mean blood glucose level [6.00 (5.74, 6.70) vs. 9.51 (8.74, 10.01) mmol/L, P<0.001], the standard deviation of glucose level [1.58 (1.11, 2.15) vs. 2.20 (1.21, 2.76) mmol/L, P=0.028], and the glycemic lability index [175.52 (100.51, 346.69) vs. 408.51 (205.56, 651.91) mmol2/(L2·h·d), P<0.001] were all smaller in the trial group than those in the control group. The percentage of blood glucose values within the target range was 77.34% in the trial group and 5.33% in the control group, respectively, and the difference was statistically significant (P<0.001). No patients experienced severe hypoglycemia. There was a significant difference in the incidence of abnormal hyperglycemia between the two groups (5.08% vs. 36.16%, P<0.001). Conclusions Hyperinsulinemic normoglycemia strategy can effectively and safely provide normoglycemia, reduce glycemic variability, and achieve good glycemic control in critically ill patients. Hyperinsulinemic normoglycemia strategy may be a new approach to glycemic control in critically ill patients.
Objective To study the interferencing and anti-tumor effects of lentiviral vector of siRNA targeting IGF1R and EGFR gene of the liver cancer cell. Methods The complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed, synthesized and connected to the pLVTHM vector, named pLVTHM-IGF1R, into whom the EGFR-siRNA expression frame containing H1 promotor synthesized by RT-PCR was cloned to generate pLVTHM-IGF1R-EGFR-siRNA. The 293T cells were cotransfected by 3 plasmids of pLVTHM-IGF1R-EGFR-siRNA, psPAX2 and pMD2G to enclose LVTHM-IGF1R-EGFR-siRNA, which was amplified in large amount and purified by caesium chloride density gradient centrifugation for measurement of virus titer. SMMC7721 cells infected by LVTHM-IGF1R-EGFR-siRNA were infection group, the untreated SMMC7721 cells and blank vector plasmid LVTHM were two control groups (SMMC7721 cell group and blank vector group). The effect of LVTHM-IGF1R-EGFR-siRNA on IGF1R and EGFR expressions of SMMC7721 cells were detected by RT-PCR and Western blot. The antitumor potential of LVTHM-IGF1R-EGFR-siRNA to SMMC7721 cells was evaluated by Cell Counting Kit-8 assay for cell growth and TUNEL for apoptosis respectively. Results LVTHM-IGF1R-EGFR-siRNA was constructed successfully. Functional pfu titers of LVTHM-IGF1R-EGFR-siRNA was 4.58×109 pfu/ml. Protein and mRNA expression of IGF1R and EGFR of infection group were less than those of blank vector group and SMMC7721 cell group （P＜0.05）, LVTHM-IGF1R-EGFR-siRNA was more effective to inhibit the proliferation and promote apoptosis of SMMC7721 cells （P＜0.05）. Conclusion LVTHM-IGF1R-EGFR-siRNA expressing IGF1R-EGFR-siRNA can inhibit the expression of IGF1R and EGFR, and may be used for further investigation of gene therapy of liver cancer.
Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the long-acting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present. Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept. 2010), MEDLINE (1950 to Sept. 2010) and CNKI (2000 to Sept. 2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves. Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included. The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves. Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar. It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.
Objective To establish hepatocellular carcinoma (HCC) cell lines which olig-expressed IGF1R gene stably． Methods An eukaryotic expressing vector pSUPER-IGF1R-siRNA that could block IGF1R expressing was transferred into hepatocellular carcinoma cell lines SMMC7721 and Hep3B with Lipofectamine 2000 reagents． After transferred, cells were selected with G418 to obtain positive clones. The expressions of IGF1R, cyclin D1 and cyclin B1 were detected by RT-PCR and Western-blot． Cell growth curve were painted. Results Two cell lines clones were screened olig-expressing IGF1R gene stably． The experimental cell lines grew more slowly than control cell lines and the expression of cyclin D1 decreased (P＜0.05). Conclusion The HCC cell lines for olig-expressing IGF1R gene stably are established successfully．The plasmid pSUPER-IGF1R-siRNA can inhibit the growth of SMMC7721 and Hep3B cell lines, and the expression of cyclin D1.
Objective To assess the effectiveness and safety of biphasic insulin aspart 30 given three times a day in the management of type 2 diabetes. Methods Such databases as CENTRAL, MEDLINE, PubMed and CNKI were searched on computer; additionally, the relevant conference proceedings from associations like American Diabetes Association, and the references of all selected literatures were also hand-searched. The randomized controlled trials (RCTs) on biphasic insulin aspart 30 given three times a day in treating type 2 diabetes were screened according to inclusive and exclusive criteria, without concerning the limitation of languages and blind methods. After data extraction and quality evaluation, Meta-analysis was performed by using RevMan 4.2 software. Results Ten trials involving 1 415 patients were included. The sub-group analysis showed that compared with the group of given biphasic insulin aspart 30 twice a day (the bid group), the group of given biphasic insulin aspart 30 three times a day (the tid group) was superior in decreasing HbAlc (Plt;0.000 01). Compared with the group of thrice preprandial injection of Novolin R plus one injection of Novolin N at bedtime (the qid group), Meta-analysis showed that, a) As to the average fasting glucose levels: the tid group was not superior to the qid group (P=0.65); b) As to the average 2-hour postprandial glucose levels: the tid group was superior to the qid group (P=0.0003); c) As to the therapeutic time: the tid group was not superior to the qid group (P=0.38); d) As to the insulin doses: the tid group was superior to the qid group (P=0.000 1); e) As to the insulin costs: the tid group was inferior to the qid group (P=0.02); and e) As to the incidence of hypoglycaemia: the tid group was superior to the qid group (P=0.000 2). Compared with the oral antidiabetic drugs, the results of Meta-analyses showed: the tid group was superior in decreasing HbAlc (P=0.001). Conclusion The limited current evidence shows that biphasic insulin aspart 30 given three times a day, as a simple insulin intensified scheme, is safe and effective for type 2 diabetes, and is worth recommending in clinic. However, all these findings should be further confirmed with more large sample and well-designed RCTs.