1.Effects of vacuum sealing drainage combined with irrigation of oxygen loaded fluid on wounds of pa- tients with chronic venous leg ulcers.
Huangding WEN ; Zhiqing LI ; Meiguang ZHANG ; Jiahan WANG ; Guifang WANG ; Qi WU ; Sen TONG
Chinese Journal of Burns 2015;31(2):86-92
OBJECTIVETo evaluate the therapeutic effects of VSD combined with irrigation of oxygen loaded fluid on the growth of granulation tissue and macrophage polarization in chronic venous leg ulcers.
METHODSThiry-four patients with chronic venous leg ulcers hospitalized in our department from December 2010 to July 2014 were divided into VSD group ( A, n = 11) , VSD + irrigation group ( B, n = 11) , and VSD + oxygen loaded fluid irrigation group ( C, n = 12) according to the random number table. After admissian, debridement was performed, and granulation tissue in the center of the wound was harvested during the operation. After dehridement, the patients in group A were treated with VSD only (negative pressure from -30 to -25 kPa, the same below) ; the patients in group B were treated with VSD combining irrigation of normal saline; the patients in group C were treated with VSD combining normal saline loaded with oxygen irrigation (flow of 1 L/min) . On post treatment day (PTD) 7, the VSD devices were removed. Cross observation was conducted before debridement and on PTD 7. On PTD 7, the granulation tissue in the center of the wound was harvested for histopathological observation with HE staining and Masson staining, following calculation of granulation tissue coverage rate. After debridement but before the negative pressure therapy (hereinafter referred to as before treatment) and on PTD 7, partial pressure of oxygen of the skin around the wound was measured by transcutaneous tissue oxygen tension survey meter. On PTD 7, expression of vascular endothelial growth factor (VECF) was determined with immunohistochemistry. Before treatment and on PTD 7, cells with double positive expressions of induced nitric oxide synthase plus CD68 ( type I macro- phage) and arginase 1 plus CD68 ( type II macrophage) were observed with immunofluorescence staining and quantified. Data were processed with Fisher's exact test, one-way analysis of variance, covariance analysis, paired test, and LSD test.
RESULTS(1) The gross observation showed that before debridement there was a certain amount of necrotic tissue and little granulation tissue in the wounds of patients in all the 3 groups. On PTD 7, new granulation tissue was found in the wounds of patients in all the 3 groups, and in group C its amount was the largest. (2) On PTD 7, the granulation tissue coverage rate of wounds in pa- tients of group C was higher than that of group A or B ( P <0.05 or P <0.01). (3) On PTD 7, HE staining showed that there appeared more abundant new born microvessels and fibroblasts in the wounds of patients in group C than those in groups A and B; Masson staining showed that there was more abundant fresh collagen distributed orderly in the wounds of patients in group C compared with group A or B. (4) On PTD 7, it was found that partial pressure of oxygen of the skin around the wounds in patients of group C [(40.7 +/- 4.1) mmHg, 1 mmHg = 0.133 kPa] was higher than that of group A [ (35.0 +/- 3.1) mmHg] or B [(35.4 +/- 2.7) mmHg, with P values below 0.01]; the partial pressure of oxygen of the skin around the wounds of patients in all the 3 groups was increased significantly compared with that before treatment (with values from 10.38 to 22.52, P values below 0.01). (5) On PTD 7, the expression of VECF in the wounds of patients in group C was higher than that in group A or B ( P <0.05 or P < 0.01). (6) On PTD 7, the number of type I macrophages in granulation tissue of patients was respectively 14.3 +/- 2.3, 11.5 +/- 3.0, and 10.7 +/- 2.3 per 400 times vision field in groups A , B, and C ( F = 25.14, P < 0.01), while the number in group C was less than that in group A or B ( P < 0.05 or P < 0.01). Compared with that before treatment, the number of type I macrophages was significantly decreased on PTD 7 in all the 3 groups (with values from 14.76 to 23. 73, P values below 0. 01). On PTD 7, the number of type II macrophages in granulation tissue of patients was respectively 32.7 +/- 3.2, 35.1 +/- 3.3 , and 41.3 +/- 3.2 per 400 times vision field in groups A, B, and C ( F = 81.10, P < 0.01), and the number in group C was lager than that in group A or B ( with P values below 0. 01). Compared with that before treatment, the number of type II macrophages in all the 3 groups was significantly increased (with t values from -69.34 to -47.95, P values below 0.01).
CONCLUSIONSVSD combined with irrigation of oxygen loaded fluid can raise the partial pressure of oxygen of the skin around the wounds effectively, promoting the transition of macrophages from type I to type II, thus it may promote the growth of granulation tissue, resulting in a better recipient for skin grafting or epithelization.
Debridement ; Drainage ; Granulation Tissue ; Humans ; Leg Ulcer ; etiology ; surgery ; Macrophages ; Microvessels ; Negative-Pressure Wound Therapy ; methods ; Nitric Oxide Synthase Type II ; Oxygen ; Skin ; Skin Transplantation ; Skin Ulcer ; Surgical Flaps ; Treatment Outcome ; Vacuum ; Vascular Endothelial Growth Factor A ; Veins ; Wound Healing
2. Role of bile acid on maintaining metabolic homeostasis
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(8):1126-1130
Bile acids are the main products of the cholesterol degradation in the liver. They promote the absorption and transportation of the intestinal lipids. Diverse bile acid receptors are widely distributed in human tissues and organs, including farnesoid X receptor (FXR) and Takeda G protein receptor (TGR5). The expression pattern of different bile acid receptors and their different affinities to various bile acids as their ligands determines their pleiotropic downstream effects, including regulating bile acid synthesis and transportation, immune and metabolism homeostasis. In addition, the bile acid pool includes components derived from both host and gut microbiota, which collaboratively contribute to the bile acid signaling activation in different compartments. Therefore, bile acid pool represents an information hub allowing the crosstalk between the host and gut microbiome and hereby modulating host metabolic homeostasis and gut microbiome symbiosis. This article reviews the recent advances in the field of bile acid regulation and the related mechanisms of bile acid signaling pathway to maintain metabolic homeostasis.
3.Inhibitory effect of apatinib on HL-60 cell proliferation and its mechanism.
Shu LIANG ; Xiu-zhen TONG ; Li-wu FU
Journal of Southern Medical University 2011;31(5):871-874
OBJECTIVETo investigate the effect of apatinib, a small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, on the proliferation of human acute myeloid leukemia HL-60 cells and explore the possible mechanism.
METHODSMTT assay was used to assess the cytotoxicity of apatinib in HL-60 cells. The apoptosis and cell cycle changes of the cells in response to apatinib treatment were analyzed by flow cytometry, and Western blotting was used to assay P-Akt and P-Erk1/2 expressions in the cells.
RESULTSApatinib significantly inhibited the proliferation of HL-60 cells in vitro with an IC(50) of 4.96∓0.32 µmol/L. Apatinib treatment significantly increased the apoptotic rate of the cells in a dose-dependent manner, but produced no significant effect on the cell cycle (P>0.05). Western blotting showed that the expressions of P-Akt and P-Erk1/2 decreased in HL-60 cells after a 48-h apatinib treatment.
CONCLUSIONApatinib inhibits the proliferation of HL-60 cells by inducing cell apoptosis probably through the mechanism of inhibiting the expressions of the Akt/Erk1/2 signal transduction pathway.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; HL-60 Cells ; Humans ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyridines ; chemistry ; pharmacology
5.Significance of EGFR and p-ERK expression in nasopharyngeal carcinoma.
Shu-sen WANG ; Zhong-zhen GUAN ; Yan-qun XIANG ; Bo WANG ; Tong-yu LIN ; Wen-qi JIANG ; Li ZHANG ; Hui-zhong ZHANG ; Jing-hui HOU
Chinese Journal of Oncology 2006;28(1):28-31
OBJECTIVETo detect the expression of EGFR and p-ERK in nasopharyngeal carcinoma (NPC) and investigate their clinical significance.
METHODSImmunohistochemistry LSAB method was adopted to detect the expression of EGFR and p-ERK. Statistical analysis was performed using SPSS statistical software package (10.0) to correlate their expression with clinical characteristics and prognosis.
RESULTSPositive staining for EGFR was observed in 39 of 55 cases (70.9%). The EGFR expression was correlated with clinical stage and gender. EGFR expression was correlated with poorer overall survival (OS) and shorter time to progression (TTP). Positive staining for p-ERK was observed in 29 of 55 cases (52.7%). There was a statistically significant association between positive p-ERK expression and advanced clinical stage. Positive p-ERK expression was correlated with poorer OS, disease-free survival (DFS) and TTP. EGFR expression was correlated with the expression of p-ERK. On multivariate analysis, age over 50 years was an independent poor prognostic factor for NPC. Both EGFR and p-ERK were not independent prognostic factors for NPC.
CONCLUSIONExpressions of EGFR and p-ERK are detected in NPC. Their abnormally high expression signifies poor prognosis in NPC patients.
Age Factors ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinases ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor ; metabolism ; Sex Factors ; Survival Rate
6.Critical Care Medicine 2017: Bigger Picture, Better Future.
Chinese Medical Journal 2017;130(10):1135-1136
7.Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis
Shu Yi WANG ; Wei Sen ZHANG ; Chao Qiang JIANG ; Ya Li JIN ; Tong ZHU ; Feng ZHU ; Lin XU
Diabetes & Metabolism Journal 2024;48(1):134-145
Background:
Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.
Methods:
Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.
Results:
During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.
Conclusion
Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.
8.Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis
Shu Yi WANG ; Wei Sen ZHANG ; Chao Qiang JIANG ; Ya Li JIN ; Tong ZHU ; Feng ZHU ; Lin XU
Diabetes & Metabolism Journal 2024;48(1):134-145
Background:
Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.
Methods:
Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.
Results:
During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.
Conclusion
Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.
9.Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis
Shu Yi WANG ; Wei Sen ZHANG ; Chao Qiang JIANG ; Ya Li JIN ; Tong ZHU ; Feng ZHU ; Lin XU
Diabetes & Metabolism Journal 2024;48(1):134-145
Background:
Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.
Methods:
Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.
Results:
During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.
Conclusion
Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.
10.Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells.
He-lin DING ; Ying GUO ; Ming-tong XU ; Hai-yan LI ; Zu-zhi FU
Chinese Medical Journal 2007;120(21):1886-1889
BACKGROUNDThe decreased degradation of extra-cellular matrix proteins plays an important role in the onset of diabetic nephropathy. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are members of the matrix metalloproteinase family, are associated with this process. Angiotensin II (AII) plays an important role in the development of diabetic nephropathy also. This research aimed to investigate the effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of MMP-9 and TIMP-1 in rat mesangial cells.
METHODSRat mesangial cells were cultured and divided into 5 groups: normal glucose (group NG), high glucose (group HG), group NG + AII, NG + AII + saralasin (group NG + AII + S, saralasin is the AII receptor blocker) and HG + saralasin (group HG + S). After the cells were incubated for 24 hours, AII concentrations in the supernatant were measured by radioimmunoassay and the expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTSAII concentrations were higher in group HG ((56.90 +/- 13.54) pg/ml) and group HG + S ((51.30 +/- 5.96) pg/ml) than in group NG ((37.89 +/- 8.62) pg/ml, P < 0.05), whereas there was no significant difference between group HG and group HG + S. The expression of MMP-9 mRNA and MMP-9/TIMP-1 mRNA ratio in group NG + AII (MMP-9, 0.33 +/- 0.04; MMP-9/TIMP-1, 0.40 +/- 0.06) and group HG (MMP-9, 0.36 +/- 0.02; MMP-9/TIMP-1, 0.45 +/- 0.03) were decreased more significantly than those in group NG (MMP-9, 0.72 +/- 0.02; MMP-9/TIMP-1, 1.21 +/- 0.07). These values in group NG + AII + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.18 +/- 0.05) were higher than those in group NG + AII, and the values in group HG + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.16 +/- 0.05) were higher than those in group HG (all were P < 0.05). TIMP-1 mRNA expression was increased more significantly in group NG + AII (0.81 +/- 0.03) and group HG (0.80 +/- 0.03) than in group NG (0.59 +/- 0.02), but it was lower in group NG + AII + S (0.60 +/- 0.01) than in group NG + AII and also lower in group HG + S (0.61 +/- 0.01) than in group HG (all were P < 0.05).
CONCLUSIONSHigh glucose stimulates AII production. Both high glucose and AII induce a decrease in MMP-9 mRNA expression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA expression, which can be reversed by saralasin, suggesting that high glucose can aggravate impaired matrix degradation by altering gene expression of MMP-9 and TIMP-1 and that the effect of high glucose may be mediated by AII.
Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Angiotensin Receptor Antagonists ; Animals ; Cells, Cultured ; Gene Expression ; drug effects ; Glucose ; pharmacology ; Matrix Metalloproteinase 9 ; genetics ; Mesangial Cells ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Saralasin ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; genetics