1.Expression of MCP-1 in renal tissues of patients with IgA nephropathy
Yongchao SUN ; Shuguang YUAN ; Xiangqing XU
Journal of Central South University(Medical Sciences) 2009;34(10):1023-1028
Objective To investigate the differential expression of monocyte ehemoattraetant protein-1 (MCP-1) in renal biopsy tissues of patients with IgA nephropathy, and to analyse the association between these 2 markers and their effect on various pathologic types of IgA nephropathy. Methods According to pathologic type, 88 renal biopsy tissues of patients with IgA nephropathy were divided into 4 groups: a minimal change group, a mesangial proliferative glomerulonephritis group, a focal sclerosing glomerulonephritis group, and a diffused sclerosing glomerulonephritis group. Immunohistochemical staining was used to detect the in situ expression of MCP-1 and CD68 on renal biopsy tissues. The expression levels were semi-quantified by image analysis and clinical data were collected from the patients. Results The differences in glomerular MCP-1 expressions were not statistically significant among all groups, while the tubulointerstitial MCP-1 expressions were statistically different among the 4 groups, with the average scores of 1.43 ± 0. 60, 5.98 ±0.92, 10. 60 ± 0.76 and 11.65 ±0.39 for minimal change group, mesangial proliferative glomerulonephritis group, focal sclerotic glomerulonephritis, and diffused sclerotic glomerulonephritis group, respectively. The tubular and interstitial CD68 scores were 0. 75 ± 0. 71, 5. 87 ± 0. 96, 10. 42 ± 0. 61, and 11.40 ±0.49 for the 4 groups, with significant differences in both MCP-1 and CD68 among the 4 groups. Correlation analysis indicated a positive correlation between tubulointerstitial MCP-1 and CD68 (r = 0. 688, P < 0. 01) . MCP-1 in tubulointerstitial was significantly correlated with 24 h urinary protein excretion (r=0.531, P<0.01). Conclusion MCP-1 plays a critical role in mac-rophage infiltration in the kidney. MCP-1 is associated with the severity of tubulointerstitial damage and clinical prognosis.
2.EXPRESSION OF THE DMBT1 GENE IN COLON CARCINOMA AND ITS CLINICAL SIGNIFICANCE
Xiangqing YUAN ; Duanqi LIU ; Yueyin WANG
Medical Journal of Chinese People's Liberation Army 2001;0(10):-
To study the relationship between the expression of the DMBT1 gene in colon carcinoma and its clinical significance. Expression of the DMBT1 gene in colon carcinoma was measured by reverse transcriptase polymerase chain reaction (PT PCR). RT PCR amplification demonstrated that 13 of 36 (36 1%) cases showed an apparent reduction in DMBT1 mRNA in tumor tissues compared with paired normal tissues. Furthermore, the expression of the DMBT1 gene mRNA was reduced in the tumor tissues with lymph nodes metastasis, depth invasion and Dukes`s classification ( P
4.Relationship between sorafenib's side effects and efficacy in treatment of advanced renal cell carcinoma patients
Zhihong CHI ; Xinan SHENG ; Hongyun LIAN ; Lu SI ; Chuanliang CUI ; Xiangqing YUAN ; Jun GUO
Chinese Journal of Urology 2009;30(1):28-31
Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.
5.Predictive factors of sorafenib in the treatment of metastatic renal cell carcinoma
Xinan SHENG ; Zhihong CHI ; Hongyun LIAN ; Xiangqing YUAN ; Lu SI ; Chuanliang CUI ; Jun GUO
Chinese Journal of Urology 2009;30(1):25-27
Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.
6.Correlation of urinary podocyte number and glomerular podocalyxin expression with clinicopathology in IgA nephropathy patients
Wenling JIANG ; Youming PENG ; Hong LIU ; Shuguang YUAN ; Xiangqing XU ; Yuncheng XIA ; Fuyou LIU
Chinese Journal of Nephrology 2010;26(8):589-593
Objective To examine the correlation of urinary podocyte number and giomerular podocalyxin expression with clinicopathology in IgA nephropathy(IgAN)patients. Methods Morning urinary specimens(100 ml)3 days before renal biopsy from 50 patients with IgAN diagnosed by renal biopsy and from 20 healthy volunteers as control were collected. After centrifugation, 300 μI sediment was used for smear. Immunohistochemical staining with monoclonal anti-podocalyxin antibody was performed to detect urinary podocytes and the number of podocyte was counted under optical microscope. Computer image analysis system was used to examine glomerular PCX expression. Renal pathology and classification were investigated based on Lee's grading and Katafuchi semi-quantitative integration method. Relevance analysis was carried out on urinary podocyte number, glomerular PCX expression with pathological score and clinical data. Results The amount of urinary podocytes in IgAN was obviously higher than that in healthy controls(P<0.01). Significant differences were found in multiple comparison of the median of urinary podocytes among Lee's grade groups. I - II group was lower as compared to Ⅲ , Ⅳ, Ⅴ groups(all P<0.05). Ⅲ group was lower as compared to V group(P<0.05). The positive rate of urinary podocyte was the highest in Ⅳ and V groups(100%), while the lowest in Ⅰ - Ⅱ group(55%). Glomerular PCX expression in IgAN decreased with the aggravation of renal pathology. Significant differences were found in multiple comparison of the glomerular PCX expression with the pathological score. Lee's Ⅰ - Ⅱ group was higher as compared to Ⅲ, Ⅳ, Ⅴ groups(all P<0.05). Ⅳ and Ⅳ groups were higher as compared to V group(P<0.05). In IgAN, urinary podocyte excretion was negatively correlated with glomerular PCX expression(r=-0.702, P<0.01), positively correlated with 24-hour urinary protein(r=0.465, P<0.01)and positively correlated with glomerular and tubular scores(r=0.233, 0.307, P<0.05). Glomerular PCX expression was negatively correlated with 24-hour urinary protein(r=-0.367,P<0.05)and negatively correlated with glomerular and tubular scores(r =-0.560, -0.377, P <0.05). Conclusions Injury and desquamation of glomerular podocytes may involve in the development of IgAN. The number of urinary podocyte can reflect the loss of podocytes in renal tissue, which may be used as a marker of disease progression of IgAN.
7.Regression analysis of glycated albumin in two successive months and hemoglobin A1c in diabetes pa-tients
Jiapei LI ; Tao YUAN ; Weigang ZHAO ; Yong FU ; Yingyue DONG ; Xiangqing WANG ; Tao XU ; Xinqi CHENG
Chinese Journal of Clinical Nutrition 2016;24(2):82-85
Objective To explore the relationship between glycated albumin ( GA ) in 2 consecutive months and hemoglobin A1c ( HbA1c) in diabetes patients.Methods Totally 100 consecutive patients with main diagnosis of diabetes mellitus were enrolled retrospectively from April 2015 to January 2016 in outpatient clinic of endocrinology of Peking Union Medical College Hospital, who had undertaken GA tests every 4 weeks for 2 successive months and had HbA1c test in the second month.GA was measured with liquid enzymatic method. HbA1c was measured by ion-exchange high performance liquid chromatography.The relationship between HbA1c and GA for the 2 successive months was determined.Results A total of 85 patients were enrolled.The regres-sion equation between HbA1c (y) and average GA (j) for successive 2 months was y=3.187+0.218j (adjusted R2 =0.520, P=0.000), which showed a similar effect as the regression equation for HbA1c and the levels of GA tested for the 2 successive months (adjusted R2 =0.514, P=0.000), and both had more significant regressive effect than the regression equation for HbA1c and single measurement of GA (adjusted R2 =0.392, P=0.000). Conclusions The regressive effect between HbA1c and GA (or the average of GA) in successive 2 months is bet-ter than that with single measurement of GA, hence could better predict HbA1c in clinical practice.
8.Secretion of glucagon and glucagon-like peptide-1 in different glucose tolerance status during pregnancy
Xiangqing WANG ; Tao YUAN ; Weigang ZHAO ; Yong FU ; Yingyue DONG ; Jie HE
Chinese Journal of Clinical Nutrition 2015;23(4):195-202
Objective To evaluate the clinical and biochemical characteristics of pregnant women with different glucose tolerance status,and their secretion characteristics of insulin,glucagon and glucagon-like peptide-1 (GLP-1) after oral glucose challenge.Methods We analyzed 74 cases pregnant women with positive results of 50 g glucose challenge test in 24-28 gestational weeks,who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test (OGTT) was performed,based on which the included women were divided into three groups,namely gestational diabetes mellitus (GDM) group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The general clinical data and biochemical indexes of the three groups were compared,and the indexes about insulin resistance and the function of pancreatic islet beta cells were calculated.Glucose,insulin,glucagon and GLP-1 were measured in OGTT.The secretion characteristics of each of these hormones and their correlation with other indicators were evaluated.Results Compared with the NGT group,the GCT [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P <0.05] and glycosylated hemoglobin A1c [(5.39±0.34)% vs.(5.18 ±0.20)%,P<0.05] were significantly higher in the GDM group.In OGTT,the area under curve (AUC) of glucose in the GDM group was significantly higher than that inthe IGT group and NGT group [(26.58 ±2.02) mmol/(L · h) vs.(23.20 ± 1.51) mmoL/(L · h),(26.58 ± 2.02) mmol/(L · h) vs.(19.84 ± 1.95) mmol/(L · h),both P < 0.05].The peak values of insulin secretion in the GDM group and IGT group were delayed to 2 hours after OGTT.The 3-hour insulin level in the GDM group was significantly higher than that in the NGT group (P < 0.05).Compared with the NGT group,the glucagon levels in each time point after OGTT and the AUC of glucagon levels were reduced in the GDM group and the IGT group,but with no significant differences.The peak glucagon levels in the 3 groups all appeared at 3 hours after OGTT.The GLP-1 levels in each time point of OGTT were gradually increased from the NGT group to the IGT group to the GDM group,but no significant differences were found.The peak value of GLP-1 level was presented at 1 hour after OGTT in the NGT group and the IGT group and at 2 hours after OGTT in the GDM group.The valley values of GLP-1 level in the 3 groups all appeared at 3 hours after OGTT.In comparison with the NGT group,the ratios of GLP-1 to blood glucose levels (GLP/BG) at 1-hour and 2-hour were significantly decreased in the GDM group (P < 0.05).The AUC of glucagon levels in OGTT were negatively correlated with fasting blood glucose (r =-0.287,P =0.013) and 1-hour glucose levels (r =-0.266,P =0.022) in OGTT and positively correlated with insulin secretion sensitivity index (ISSI) (r =0.297,P =0.010) and HOMA-β (r =0.236,P =0.043).Moreover,the AUC of GLP-1 levels in OGTT was negatively correlated with the levels of C-reactive protein (r =-0.264,P =0.035).The AUC of GLP/BG in OGTT was positively correlated with ISSI (r=0.406,P<0.001).Conclusions Pregnant women with GDM and IGT in the second trimester have insulin resistance and dysfunction of pancreatic islet β cells.Potential GLP-1 resistance and inadequate secretion may exist in GDM patients.GLP/BG may be a better parameter to evaluate the secretion function of L cells in pregnancy and an effective parameter to estimate the compensatory function of pancreatic β cells indirectly.Glucagon levels may not start to change obviously before 28 gestational weeks.
9.Serum adipocytokines in pregnant women with different glucose metabolism status
Tao YUAN ; Xiangqing WANG ; Weigang ZHAO ; Yong FU ; Yingyue DONG ; Jiapei LI
Chinese Journal of Clinical Nutrition 2015;23(4):203-208
Objective To evaluate clinical features,insulin sensitivity,and serum adipocytokines levels in pregnant women with different glucose tolerance status and to investigate the possible serum predictive biomarkers of gestational diabetes mellitus (GDM).Methods We included 74 pregnant women with positive results of 50 g glucose challenge test (GCT),who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test was performed in 24-28 gestational weeks,based on which the 74 pregnant women were divided into GDM group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The clinical data were recorded in detail.Serum fibroblast growth factor (FGF)-19,FGF-21,visceral adiposespecific serine protease inhibitor (vaspin),leptin,insulin-like growth factor binding protein-1 (IGFBP-1),and adiponectin levels of the 3 groups were measured by enzyme-linked immunosorbent assay (ELISA) and compared.The associations of these adipocytokines with the patients' baseline data and metabolic indexes were analyzed.Results The blood glucose after GCT and glycosylated hemoglobin A1c in the GDM group were significantly higher than those in the NGT group [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P <0.05;(5.39 ± 0.34) % vs.(5.18 ± 0.20) %,P < 0.05],but not significantly different from those in the IGT group [(9.14 ± 0.64) mmol/L,P > 0.05;(5.28 ± 0.28) %,P > 0.05].Age,systolic blood pressure and diastolic blood pressure in the first trimester,pre-gestational body mass index (BMI),increment of BMI during pregnancy,serum total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,and C-reactive protein levels in the three groups showed no significant differences (all P >0.05).From the NGT group to the IGT group to the GDM group,the area under curve of blood glucose (AUCBG) [(19.84±1.95),(23.20±1.51),(26.58±2.02) mmol/(L · h)] and AUC of insulin (AUCINS) [(1.84± 0.91) ×103,(1.85 ±1.15) ×103,(2.49 ±1.36) ×103 pmol/(L · h)] both gradually increased.Compared with the NGT group,the GDM group had significantly higher HOMA-IR [3.0 (1.5,5.2) vs.2.5 (1.5,3.4),P <0.05] significantly lower HOMA-β [230.5 (144.6,311.6) vs.235.6 (168.1,350.0),P < 0.05].Among the GDM,the IGT,and the NGT groups,there were no significant differences in serum FGF-19 [(284.42±78.16),(268.17 ±72.97),(283.86 ±79.74) ng/L],FGF-21 [(798.16±273.57),(882.43 ±322.17),(842.75 ±343.01) ng/L],vaspin [(22.36 ±7.27),(23.53 ±7.90),(22.63±9.11) μag/L],leptin [(5.51 ± 1.44),(5.58 ± 1.58),(5.48 ± 1.47) μg/L],adiponectin [(798.85 ± 255.14),(863.44 ± 252.18),(828.36 ± 249.32) μg/L] and IGFBP-1 [(40.44 ± 16.41),(49.57±12.60),(43.80±16.58) μg/L] levels (all P>0.05).Conclusions There are no significant differences of a variety of adipocytokines in pregnant women with different glucose tolerance status,and no effective serum predictors of GDM are found.The effect of adipocytokines in the pathogenesis of GDM remains to be further investigated.
10.Diagnostic value of renal phospholipase A2 receptor and serum anti-phospholipase A2 receptor antibody in membranous nephropathy
Xiaoxiang WU ; Si WEN ; Xuejing ZHU ; Shuguang YUAN ; Xiangqing XU ; Danyi YANG ; Lin SUN ; Hong LIU ; Fuyou LIU
Journal of Central South University(Medical Sciences) 2017;42(4):395-399
Objective:To examine the expression ofphospholipase A2 receptor (PLA2R) in renal tissues and the level of anti-PLA2R antibody in serum in patients with idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (SMN),and to evaluate their diagnostic value in IMN.Methods:A total of 73 patients,who were diagnosed between May,2014 and February,2015 in the Department of Nephrology of the Second Xiangya Hospital,Central South University,were divided into three groups:an IMN group (n=48),an SMN group (n=17) and a minimal change disease group (n=8) according to the renal biopsy.PLA2R expression in renal tissues and the level of antiPLA2R antibody in serum were detected by indirect immunofluorescence technique.Results:The positive rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group were higher than those in the SMN group (91.7% in the IMN group vs 29.4% in the SMN group,P<0.05),while the positive rate and serum level for anti-PLA2R antibody in the IMN group were higher than those in the SMN group (85.4% in the IMN group vs 29.4% in the SMN group,P<0.05);the expression of PLA2R in renal tissues and the serum level for anti-PLA2R antibody were not detected in the minimal change disease group,The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (r=0.432,P<0.01) and negatively correlated with serum albumin (r=-0.307,P<0.05).Conclusion:The expression of PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be potential markers for diagnosis oflMN.