1.Invasion of tumor associated macrophages and its influence on the prognosis in cardia carcinoma
Xuefeng XU ; Yaowu CAI ; Chaoqing HUANG ; Hanxing HUANG ; Xintong CHEN
Cancer Research and Clinic 2021;33(5):344-348
Objective:To explore the association of tumor associated macrophages (TAM) with tumor invasiveness, metastasis and prognosis in cardia carcinoma tissues.Methods:The cancer tissues and pericarcinomatous tissues of 100 patients with cardia carcinoma who underwent D2 radical operation in the First Hospital of Putian City from January 2014 to January 2015 were collected. M2-type TAM was marked with CD163. The tissue microarray was made and the expression of CD163 in microarray tissues was detected by using immunohistochemistry. The median number of CD163 positive cells in all cancer tissues was taken as the cut-off value. The patients with the mean number of CD163 positive cells ≥ the cut-off value were those with high TAM infiltration, and vice versa. The association of TAM infiltration with clinicopathological features and prognosis was analyzed, and Cox proportional hazards model was used for multivariate analysis of survival.Results:The positive cell median number of CD163 in cardia carcinoma tissues was higher than that in adjacent tissues [the median number ( P25, P75): 32/high power field (HP) (16/HP, 46/HP) vs. 6/HP (4/HP, 11/HP)], and the difference was statistically significant ( Z = -35.044, P < 0.01). There were 48 cases in low invasive group (< 32/HP) and 52 cases in high invasive group (≥32/HP). The proportion of patients with high TAM infiltration in serosa and extraserosa was higher than that in mucosa and muscle [60.9% (39/64) vs. 36.1% (13/36)], and the proportion of patients with high TAM infiltration for patients with lymph node metastasis was higher than that for patients without lymph node metastasis [61.8% (42/68) vs. 31.3% (10/32)], and the proportion of patients with high TAM infiltration for those with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [64.4% (38/59) vs. 34.1% (14/41)], and the differences were statistically significant (all P < 0.05). The median overall survival time of high TAM group was shorter than that of low TAM group [24.00 months (95% CI 17.25-43.50 months) vs. 62.00 months (95% CI 34.00-68.00)], and the difference in overall survival was statistically significant (χ 2 = 18.137, P < 0.01). Lymph node metastasis ( HR = 0.301, 95% CI 0.105-0.862, P = 0.025), TNM staging ( HR = 8.404, 95% CI 2.810-25.133, P < 0.01) and TAM infiltration level in cancer tissues ( HR = 4.277, 95% CI 2.372-7.712, P < 0.01) were independent influencing factors for overall survival of patients. Conclusions:TAM plays an important role in the invasion and metastasis of cardia carcinoma and can be used as an independent predictor of biological behavior and prognosis in cardia carcinoma.
2.The promoter methylation of tissue inhibitor of metalloproteinase 3 in cardia carcinoma and its clinical significance
Xuefeng XU ; Jiecheng LIN ; Maosong ZHENG ; Chaoqing HUANG ; Yaowu CAI ; Hanxing HUANG
Cancer Research and Clinic 2016;28(1):36-39
Objective To explore the relations among the promoter methylation of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene and its protein expression, and the clinicopathological features in the gastric cardia carcinoma. Methods The tumor tissues and the adjacent normal mucosal tissues were collected from 65 patients with cardia carcinoma. The promoter methylation levels and the protein expression of TIMP-3 gene were detected by methylation-specific PCR (MSP) and immunohistochemistry respectively. Results The TIMP-3 methylation rates was 78.5 % (51/65) in the tumor tissues and 13.8 % (9/65) in the incisal edge of normal tissues, the methylation rates of TIMP-3 had positive correlation with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. The protein expression of TIMP-3 was 26.2 %(17/65) in the tumor tissues and 95.4 % (62/65) in the incisal edge of normal tissues (P = 0.016), the protein expression of TIMP-3 was negatively correlated with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. Conclusion The methylation of promoter region in CpG islands is a main mechanism of reduced and loss expression of TIMP-3 gene, which may play an important role in the invasion and metastasis of cardia carcinoma.
3.Tissue inhibitor of metalloproteinases 3 promoter methylation and mRNA expression in cardia carcinoma and its relationship with prognosis
Xuefeng XU ; Jiecheng LIN ; Maosong ZHENG ; Chaoqing HUANG ; Yaowu CAI ; Hanxing HUANG
Cancer Research and Clinic 2016;28(12):802-805
Objective To explore the relationship of the methylation levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) gene promoter CpG islands with the invasiveness and prognosis in cardia carcinoma. Methods The tumors tissues were collected from 65 patients with cardia carcinoma. The methylation levels of the promoter of TIMP-3 gene were detected by methylation-specific PCR (MSP), the mRNA expression levels of TIMP-3 gene were detected by RT-PCR. The relationship of TIMP-3 gene ectopic methylation with invasiveness and prognosis of the cardia carcinoma patients was analyzed. Results The positive expression rates of TIMP-3 mRNA in gastric cancer and normal gastric tissues were 53.8 % (35/65) and 96.9 % (63/65), respectively. The difference was not statistically significant(Fisher exact test, P=0.912). The positive rate of TIMP-3 mRNA was negatively correlated with the depth of tumor invasion and lymph node metastasis [mucosa and muscular vs. serosa and mucosa outside of the serosa and muscula: 83.3 % (10/12) vs. 45.3 % (24/53); with lymph node metastasis vs. without lymph node metastasis: 73.9 % (17/23) vs. 40.5 %(17/42)] (both P<0.05). There was a negative correlation between TIMP-3 gene promoter methylation and TIMP-3 mRNA expression (r=-0.276, P=0.026). The size of tumor and TIMP-3 gene promoter methylation were both the independent influencial factors of prognosis in cardia carcinoma (both P<0.05). Conclusion The methylation of promoter region in CpG islands plays an important role in the invasion and metastasis of cardia carcinoma, and it can be used as an independent predictor of biological behavior and prognosis.
4.Association of PGC-1α gene polymorphism with type 2 diabetes mellitus
Wensheng LU ; Qin HUANG ; Xiaodong YAN ; Yingyu HU ; Mei ZHONG ; Chaoqing WU
Chinese Journal of Endocrinology and Metabolism 2008;24(4):404-407
Objective To investigate the association of PGC-1 α gene single nucleotide polymorphisms (SNPs) with type 2 diabetes mellitus in Southern China Han population. Methods 350 patients with type 2 diabetes mellitus and their parents and 366 normal Han volunteers were recruited in the study. Their blood specimens were collected to extract the genornic DNA. Thr394Thr(G/A), Gly482Ser(G/A), Thr528Thr(A/G) and Thr612Met (C/T) genotypes were identified by PCR-RFLP and DNA direct sequencing. The possible association was analyzed between diabetic patients with the specific cSNPs and their haplotypes by case-control and haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods. Results (1) The case- control study indicated that G and A allele frequencies of PGC-1 α gene Gly482Ser variant were 0.589, 0.411 in type 2 diabetic group and 0.687, 0.313 in normal group respectively (X<'2> = 15.076, P < 0.01). The allele frequencies of Thr394Thr, Thr528Thr, Thr612Met polymorphisms did not show significant difference between twogroups respectively (all P > 0.05). The distributions of Thr394Thr-Gly482Ser-Thr528Thr haplotypes in the diabetic group were significanly different from the controls (X<'2> = 40.2, P < 0.05) and had a linkage disequilibrium with type 2 diabetes mellitus (t = 2.503, P < 0.05). (2) The family-basod studies showed that 482A allele was transmitted more significantly both via TDT and extended TDT from heterozygous parents to patients than expected respectively (all P < 0.05). HRR also supported that the 482A allele was more often transmitted to patients than predicted by chance (X<'2> = 7.217, P = 0.007, HRR = 1. 450). TDT analyses of haplotypes suggested that the frequencies of 394A-482A-528A-612C,394A-482A-528A-612T, 394A-482A-528G-612C and 394A-482A-528G- 612T haplotypes significantly deviated from 0.5 (P < 0.05 or P < 0.01). Conclusion In Southern China Hanpopulation, type 2 diabetes mellitus is associated with the Gly482Ser variant of PGC-1α gene, and Thr394Thr (G/ A) variant of PGC-1α gene appears to play an auxiliary role in this association.
5.The clinical value of bedside testing of plasma levels of NT-proBNP and cTnI in the rapid diagnosis of cardiac dyspnea
Tong LIAO ; Yuanchun ZHANG ; Huanlun LI ; Zhentuo GU ; Chaoqing PAN ; Lihua LU ; Zhiwei TAN ; Xifan HUANG
Tianjin Medical Journal 2016;44(10):1255-1258
Objective To explore the diagnostic value of combined bedside detection of aminoterminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in the diagnosis of cardiac dyspnea. Methods A total of 120 patients with dyspnea admitted in our department from June 2014 to February 2016 were included in this study. At the time of admission, NT-proBNP and cTnI levels were measured by bedside test. Values of NT-proBNP>300 ng/L or cTnI>0.16 mg/L were defined as positive for cardiac dyspnea. According to the final diagnosis, patients were divided into two groups:cardiac dyspnea group (n=68) and pulmonary dyspnea group (n=52). At the same time, 30 healthy people were selected as control group. Values of NT-proBNP and cTnI were used for statistical analysis between the three groups. The sensitivity and specificity of NT-proBNP, cTnI and cTnI+NT-proBNP were compared between three groups. Results The levels of NT-proBNP and cTnI were significantly higher in pulmonary dyspnea group and cardiac dyspnea group than those in the control group, and the levels were significantly higher in cardiac dyspnea group than those of pulmonary dyspnea group (P<0.01). The detection sensitivity of NT-proBNP and cTnI alone was 67.65% and 52.94%, combined detection of both was up to 94.12%. The specificity of NT-proBNP and cTnI detection alone was 70.00% and 53.33%, respectively, and combined detection of both was up to 86.67%. The sensitivity of NT-proBNP+cTnI was significantly higher than that of NT-proBNP and cTnI alone (P<0.05), but there was no significant difference in the specificity between combined detection andindividual detection of NT-proBNP. The positive predictive value of the combined detection in the diagnosis of cardiac dyspnea was 94.12%(64/68), and the negative predictive value was 86.67%(26/30). Conclusion Bedside detection with combination of cTnI and NT-proBNP has important clinical application value in the rapid diagnosis of cardiac dyspnea, which is a rapid clinical testing method.
6.Comparison of epidemiological situation in chronic kidney disease between urban and rural areas in Guangxi province
Sheng TANG ; Xiaomei PENG ; Chaoqing WU ; Wenxin ZHANG ; Haoyu WANG ; Min BI ; Yunfang LIU ; Jinyu LI ; Ling HUANG ; Zhifeng GONG
Chinese Journal of Nephrology 2011;27(12):890-895
ObjectiveTo investigate and compare the prevalence,awareness and risk factors of chronic kidney disease (CKD) between urban and rural population in Guangxi province in order to provide information for prevention and treatment of CKD.MethodsBy a stratified multistage random sampling method,18 to 74 years old residents in Guangxi province were surveyed. They wereevaluatedbyquestionnaire,urinaryalbumin/creatinineratio, hematuria (microscopic examination of centrifuged urine sediment),kidney B-mode ultrasound,and abnormal results were reviewed 3 months later.Estimated glomerular filtration rate(eGFR) was calculated with the simplified MDRD equation modified by a Chinese coefficient.The risk factors associated with CKD were also investigated.Results There were no significant differences between urban and rural residents in the prevalence of albuminuria (5.22% vs 5.47%) and hematuria (1.07% vs 1.11%)(all P>0.05).The prevalence of renal lithiasis in rural residents was significantly higher than that in the town(10.54% vs 6.95%)(P<0.05).The decreased renal function between urban and rural residents(3.87% vs 4.04%,P>0.05) had no significant difference.The prevalence of CKD was 9.58% in urban and 9.42% in rural(P>0.05).The prevalence of albuminuria according to the age distribution was different between urban and rural,which increased along with the age in urban but showed two peaks(30-40 years old and 60-74 years old) in rural.Based on logistic regression analysis,the risk factors for albuminuria were diabetes,hyperuricemia,the history of cardiovascular disease,chronic tonsillitis and HBsAg positive.The risk factors for kidney function decline were age,hyperuricemia,hypertension,diabetes,renal lithiasis and history of cardiovascular disease.The awareness rate of CKD in urban was significantly higher than that in rural (14.45% vs 6.27%,P<0.05).Conclusions The prevalenceof CKD has no significant difference between urban and rural in Guangxi province.The awareness rate of CKD in urban is significantly higher than that in rural.It is needed to enhance the prevention and treatment of CKD in rural.
7.The short-term therapeutic effects of DNA immunoadsorbent combined with medication on patients with ;severe systemic lupus erythematosus
Chaoqing WU ; Lijia XIONG ; Hongguang HE ; Yunfang LIU ; Jinyu LI ; Haoyu WANG ; Sheng TANG ; Kun YE ; Xiaomei PENG ; Ling HUANG ; Yeying TANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2014;26(2):84-87
Objective To evaluate the short-term therapeutic effects of DNA immunoadsorbent (IA) combined with glucocorticoid and immune depressant on patients with severe systemic lupus erythematosus(SLE). Methods 32 patients with severe SLE were selected to undergo DNA IA treatment combined with glucocorticoid plus cyclophosphamide therapy, and each patient received IA therapy 3 times, once 2.5 hours, with an interval of 24-48 hours to take another two times of IA. The changes in SLE disease activity index(SLEDAI)score, health status evaluation indexes〔 physiologic functional( PF) and emotional health( MH) scores〕,renal function indexes〔 blood urea nitrogen(BUN)and serum creatinine(SCr)〕 were observed; and anti-double stranded DNA antibody( ds-DNA), immunoglobulin (IgA, IgG, IgM), complements(C3 and C4)and high-sensitivity C-reactive protein (hs-CRP) were examined before and after IA treatment for 2 weeks. Results Two weeks after the combination therapy, the SLEDAI score, BUN, SCr, dsDNA, IgA, IgG, IgM, hs-CRP were significantly lower than those before treatment 〔SLEDAI score : 14.38±3.85 vs. 15.69±1.40, BUN (mmol/L): 11.22±4.78 vs. 16.31±7.90, SCr (μmol/L): 127.02±38.17 vs. 167.25±45.63, dsDNA( U/L): 1.36±0.12 vs. 1.43±0.18, IgA( g/L): 2.41±0.73 vs. 2.59±0.86, IgG( g/L): 16.82±4.83 vs. 21.01±4.84, IgM( g/L): 1.64±0.45 vs. 1.75±0.58, hs-CRP( mg/L): 14.41±2.20 vs. 14.94±2.60, P<0.05 or P<0.01〕; PF score, MH score, complement C3 were increased〔 PF score : 71.19±17.53 vs. 56.66±22.41, MH score : 74.01±15.72 vs. 61.50±17.98, C3( g/L): 0.56±0.09 vs. 0.52±0.10, all P<0.05〕; clinical symptoms were improved significantly, and no significant adverse reactions were found. Conclusion IA combined with medical treatment has shown that it has significant therapeutic effect for treatment of patients with severe SLE, and it may decrease the levels of dsDNA, IgA, IgG, IgM,hs-CRP, and increase the level of complement C3.
8.Dynamic changes of renal blood perfusion in Goto-Kakizaki rats using contrast-enhanced ultrasonography
Fang MA ; Baozhen ZHAO ; Yuanyuan LIU ; Yuanyuan DANG ; Weiping LI ; Lehang GUO ; Chen Lü ; Rong WU ; Lin YANG ; Wei YAN ; Xiao HUANG ; Chaoqing WANG
Chinese Journal of Ultrasonography 2011;20(9):803-807
Objective To explore dynamic changes of renal cortex blood perfusion in Goto-Kakizaki rats(GK rats) by contrast-enhanced ultrasonography.The clues for early diagnosis and intervention of diabetic renal impairment may be obtained from the study.Methods Male GK rats were taken as experimental groups,and Wistar male rats were used as controls.Contrast-enhanced agent SonoVue was administered via the femoral vein cannulation in a bolus fashion.Image changes of renal cortex were observed in real time, and dynamic image changes within 0 - 5 minute after injection were observed and stored.The renal cortex blood perfusion changes were analyzed using the time-intensity curve (TIC).Results (1) The kidney was quickly enhanced after the injection of contrast agent.The renal artery, cortex, renal vein were displayed in sequence.(2)The shape of renal perfusion TIC in all the objects was a single peak,steep ascending, flat descending curve.The overall shape of TIC in GK rats was wider than controls and they were wider and wider with age increasing of the GK rats.(3) Compare to controls,the time to peak (TTP)and the half time of peak descending (HDT) in GK rats was longer (P <0.01), the slope rates of the ascending curve (S1) and the slope rates of the descending curve (S2) decreased and the area under the curve increased in 12-week-old and 20-week-old GK rats (P < 0.05 or P < 0.01).Conclusions The abnormal blood perfusion of renal cortex microcirculation was present in the early stage of diabetic in GK rats.Real-time contrast-enhanced ultrasonography and TIC could display this change effectively.
9.Predictive factors analysis of the efficacy of cyclophosphamide combined with glucocorticoids in the treatment of idiopathic membranous nephropathy
Hongguang HE ; Yiyun HUANG ; Chun ZENG ; Chaoqing WU ; Kun YE ; Lijia XIONG ; Xiaomei PENG
Chinese Journal of Nephrology 2019;35(1):9-17
Objective To investigate the predictive factors affecting the efficacy of cyclophosphamide (CTX) combined with glucocorticoids in the treatment of idiopathic membranous nephropathy (IMN),and to evaluate the efficacy of calcineurin inhibitor (CNI) adjustment due to poor treatment.Methods A retrospective cohort study was conducted.Two hundreds and twenty-eight patients with IMN diagnosed by renal biopsy in the People's Hospital of Guangxi Zhuang Autonomous Region from January 1,2007 to December 1,2016 were enrolled.All subjects were treated with CTX in combination with glucocorticoids.The patients were divided into two groups:remission group and no remission group.Multivariable logistic regression analysis was used to determine the baseline clinical-pathological influencing factors for the remission of IMN in the enrolled patients.Results The number of total remission (including complete and partial remission) of the first CTX combined with glucocorticoid treatment in 228 patients with IMN was 188(82.5%).Among them,141 patients (61.8%) had complete remission (CR),the median time for CR was 8(6,12) months,and the median time for partial remission (PR) was 3(1,4) months.The median follow-up time for this study was 25(13,43) months.Compared with the remission group,the serum albumin level was lower in the non-remission group,the 24-hour urine protein content,the blood complement C3 and C4 levels were higher,and the pathological stage was milder (all P < 0.05).Multivariate logistic regression analysis suggested that the levels of baseline serum albumin,complement C4,and pathological stage were independent predictors of clinical remission in IMN patients.Twenty-four non-remission patients were treated with CNI.The overall response rate was 66.7%(16/24) at 6 months and 77.3%(17/22) at 12 months.Conclusions The levels of baseline albumin,blood complement C4,and pathological stage were independent predictors of clinical remission in IMN patients treated with CTX plus glucocorticoids.The non-remission patients with CTX combined with glucocorticoid therapy can still achieve a higher response rate after adjusting for CNI.