Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.

AIM:To observe the effects of Egr-1 gene transfection on the expression of tumor necrosis factor-α( TNF-α) and intercellular adhesion molecule-1 ( ICAM-1) , and to investigate the role of Egr-1 in the pathogenesis of dia-betic nephropathy .METHODS:The diabetic mouse model was established .Ten mice were randomly selected as the dia-betic group .The remaining 40 mice were injected with empty plasmid , Egr-1 expression plasmid or Egr-1 siRNA plasmid via the tail vein once a week.The normal control group was also set up .The animals were sacrificed at the end of the 4th week.The renal tissues were harvested .The expressions of Egr-1, TNF-αand ICAM-1 were detected by immunohisto-chemistry and Western blot .The pathological changes were observed under electron microscope .RESULTS: In diabetic mouse kidney, the expression of Egr-1, TNF-αand ICAM-1 was increased, and irregular thickening of glomerular basement membrane , mesangial expansion and fusion of foot were observed .The change trend was more significant in Egr-1 gene transfection group , and these changes in siRNA plasmid transfection group were obviously reduced compared with diabetes group.CONCLUSION:Egr-1 up-regulates the expression of TNF-αand ICAM-1, and induces mesangial cell proliferation and mesangial extracellular matrix accumulation , which is probably one of the mechanisms of accelerating glomerulosclerosis .

OBJECTIVETo investigate the effects of different concentrations of lipopolysaccharide (LPS) on proliferation and apoptosis of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, and to explore their possible mechanism.

METHODShUCMSCs from umbilical cord tissue of full-term healthy fetus delivered by caesarean section were isolated and cultured in vitro using tissue attachment method. The 3rd passage hUCMSCs were used in the study. Cells were divided into groups A, B, C, D, and E, which were treated with DMEM/F12 medium containing 0, 0.1, 1.0, 10.0, and 100.0 µg/mL of LPS respectively. In groups B, C, D, and E, methyl-thiazole-tetrazolium assay was used to detect proliferative activity of hUCMSCs at post treatment hour (PTH) 12, 24, and 48 (denoted as absorption value), with 5 samples in each group at each time point; apoptosis of hUCMSCs at PBH 24 was identified with acridine orange-ethidium bromide (AO-EB) staining, with 4 samples in each group; apoptotic rate of hUCMSCs was determined by flow cytometer, with 5 samples in each group. Above-mentioned indexes were determined in group A at the same time points. Data were processed with analysis of variance and LSD- t test.

RESULTS(1) There was no statistically significant difference in proliferative activity of hUCMSCs at PTH 12 among groups A, B, C, D, and E (with t values from -1.67 to 1.33, P values above 0.05). Compared with that of group A, proliferative activity of hUCMSCs was increased in groups B, C, and D at PTH 24 and 48 (with t values from -13.42 to 17.34, P < 0.05 or P < 0.01), especially so in group C. Proliferative activity of hUCMSCs was lower in group E at PTH 24 and 48 than in group A (with t values respectively 8.64 and 17.34, P values below 0.01). (2) Obvious apoptosis of hUCMSCs was observed in group E but not in the other 4 groups with AO-EB staining. (3) Apoptosis rates of hUCMSCs in groups A, B, C, D, and E were respectively (3.1 ± 0.6)%, (2.6 ± 0.7)%, (2.9 ± 0.8)%, (3.1 ± 0.4)%, (25.1 ± 2.7)% (F = 272.19, P < 0.01). Apoptotic rate of hUCMSCs in group B, C, or D was respectively close to that in group A (with t values respectively 1.22, 0.57, -0.14, P values above 0.05), but it was higher in group E than in group A (t = -17.63, P < 0.01).

CONCLUSIONShUCMSCs proliferation may be promoted by low concentration of LPS. hUCMSCs proliferation is inhibited or induced to apoptosis along with the increase in concentration of LPS, and it may be related to activation of different major molecular signaling pathways by different concentrations of LPS.

Apoptosis ; drug effects ; Cell Proliferation ; Endotoxins ; adverse effects ; Humans ; Lipopolysaccharides ; pharmacology ; Membrane Proteins ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Signal Transduction ; Umbilical Cord ; cytology

OBJECTIVETo explore the association of perioperative blood transfusion (PBT) with survival of gastric cancer after surgery.

METHODSWe retrospectively reviewed the medical records of 1 000 gastric cancer patients, including 738 non-transfused (73.8%) and 262 transfused (26.2%) cases. A one to one match was created using propensity score analysis, except preoperative hemoglobin level and operative blood loss. The survival was analyzed by Kaplan-Meier survival model.

RESULTSThe 5-year survival rate of the 1 000 cases of gastric cancer patients was 39.9%. Before matching, there was a significant difference between transfused group (33.6%) and non-transfused group (49.1%, P<0.005). Univariate analysis showed that age, tumor size, hemoglobin level, albumin level, depth of invasion, lymph node metastasis, lymph node dissection, surgery mode, adjuvant chemotherapy, blood loss and blood transfusion during perioperative period were associated with prognosis in the gastric cancer patients (all P<0.05). Multivariate analysis showed that tumor invasion, lymph node metastasis, lymph node dissection, chemotherapy and perioperative blood transfusion were independent prognostic factors in gastric cancer (all P<0.05). After matching, the 5-year survival rate of the 262 non-transfused patients was 37.7%, while that of the 262 transfused patients was 33.6% (P>0.05).

CONCLUSIONSPerioperative blood transfusion has no significant effect on the prognosis of gastric cancer patients.

Analysis of Variance ; Blood Transfusion ; mortality ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision ; Lymphatic Metastasis ; Perioperative Period ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; mortality ; pathology ; surgery ; Survival Rate

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.