Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumo...Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment,composed of activated fibroblasts and macrophages.Macrophages can be characterized as M1 or M2,with tumor-inhibiting or-promoting functions,respectively.We reported that Gremlin 1(GREM1),a key pro-fibrogenic factor,is upregulated in the stroma of CP.The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC.By mRNA in situ hybridization,we detected GREM1 mRNA expression withinα-smooth muscle actin(SMA)-positive fibroblasts of the pancreatic stroma.These designated FibroblastsGrem1+marginally increased from CP to pancreatic intraepithelial neoplasia(PanIN)and PDAC.Within PDAC,FibroblastsGrem1+increased with higher pathological tumor stages and in a majority of PDAC subtypes screened.Additionally,FibroblastsGrem1+positively correlated with total macrophages(MacCD68+)and M2 macrophages(M2CD163+)in PDAC.To begin exploring potential molecular links between FibroblastsGrem1+and macrophages in PDAC,we examined the expression of macrophage migration inhibitory factor(MIF),an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor.By IHC staining of MIF,we found MIF to be expressed by tumor cells,positively correlated with GREM1;by IHC co-staining,we found MIF to be negatively correlated with M2CD163+expression.Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development,and GREM1/MIF may play an important role in macrophage phenotype.展开更多
目的了解妊娠中晚期孕妇血清Gremlin1水平变化,探究Gremlin1对妊娠期糖尿病(gestational diabetes mellitus,GDM)的影响。方法选取2020年9-11月就诊于安徽医科大学第一附属医院行孕期体检的妊娠24~28周并完善口服葡萄糖耐量试验(oral gl...目的了解妊娠中晚期孕妇血清Gremlin1水平变化,探究Gremlin1对妊娠期糖尿病(gestational diabetes mellitus,GDM)的影响。方法选取2020年9-11月就诊于安徽医科大学第一附属医院行孕期体检的妊娠24~28周并完善口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)的妊娠期女性175例为研究对象,根据OGTT结果分为GDM组和糖代谢正常组(NGT组)。收集两组临床资料,包括一般资料、Gremlin1水平及其他生化指标,比较两组临床资料的差异。结果GDM组妊娠前体重、妊娠后体重、妊娠前体质量指数(body mass index,BMI)、妊娠后BMI、空腹血糖(fasting blood glouse,FBG)、1 h血糖(1 h blood glouse,1 hBG)、2 h血糖(2 h blood glouse,2 hBG)、空腹胰岛素(fasting insulin,FINS)、1 h胰岛素(1 h insulin,1 hINS)、2 h胰岛素(2 h insulin,2 hINS)、空腹C肽(fasting C protein,FCP)、1 h C肽(1 h C protein,1 hCP)、2 h C肽(2 h C protein,2 hCP)、胰岛素抵抗指数(homeostatic model assessment insulin resistance,HOMA-IR)、血糖曲线下面积(AUC-G)、胰岛素曲线下面积(AUC-I)高于NGT组,胰岛β细胞功能指数(homeostatic model assessmentβcell insulin secretion index,HOMA-β)、胰岛素敏感指数(insulin sensitivity index,ISI)低于NGT组(均P<0.05)。GDM组血清Gremlin1水平高于NGT组(P<0.05)。Pearson相关分析提示血清Gremlin1水平与妊娠后BMI、FBG、1 hBG、1 hINS、2 hBG、2 hINS、2 hCP、HOMA-IR、AUG-G、AUC-I呈正相关,与HOMA-β、ISI呈负相关(均P<0.05)。多因素Logistic回归分析提示,血清Gremlin1是GDM的独立危险因素(OR=8.922,95%CI 1.863~42.736,P<0.05)。结论GDM患者血清Gremlin1升高,并与胰岛素抵抗呈正相关,参与GDM的糖代谢。展开更多
目的:探讨Gremlin-1、血尿酸(SUA)及骨代谢指标表达水平与骨质疏松患者疾病严重程度的相关性及其联合诊断价值。方法:选取我院2019年1月到2020年12月收治的80例骨质疏松患者,对所有患者依照双X线吸收法诊断结果进行严重程度分组,将骨密...目的:探讨Gremlin-1、血尿酸(SUA)及骨代谢指标表达水平与骨质疏松患者疾病严重程度的相关性及其联合诊断价值。方法:选取我院2019年1月到2020年12月收治的80例骨质疏松患者,对所有患者依照双X线吸收法诊断结果进行严重程度分组,将骨密度-2.5<T<-1患者分为骨量减少组(n=23),将骨密度T≤-2.5患者分为骨质疏松症组(n=37),将骨密度T≤-2.5,且发生过骨质疏松性骨折的患者分为严重骨质疏松症组(n=20)。对比三组患者Gremlin-1、SUA表达水平与骨代谢指标表达水平,采用Spearman相关分析Gremlin-1、SUA及骨代谢指标表达水平与骨质疏松患者疾病严重程度的相关性。最后建立ROC曲线,Gremlin-1、SUA及骨代谢指标联合对骨质疏松症的诊断价值。结果:三组患者Gremlin-1、SUA水平对比差异显著,骨量减少组Gremlin-1高于骨质疏松症组和严重骨质疏松症组,SUA低于骨质疏松症组和严重骨质疏松症组(P<0.05);三组患者维生素D3[25-(OD)-D3]、β-胶原特殊序列(β-CTX)、甲状旁腺激素(PTH)、I型前胶原N端肽(N-terminal peptide of type I procollagen,PINP)、骨钙素(OC)相关骨代谢指标水平对比差异显著,骨量减少组25-(OD)-D3、PINP、OC高于骨质疏松症组和严重骨质疏松症组,β-CTX、PTH低于骨质疏松症组和严重骨质疏松症组(P<0.05);SUA(r=-0.636)、β-CTX(r=00.626)、PTH(r=0.625)的表达与骨质疏松患者疾病严重程度呈正相关,Gremlin-1(r=-0.452)、25-(OD)-D3(r=-0.462)、PINP(r=-0.622)、OC(r=-0.426)的表达与骨质疏松患者疾病严重程度呈负相关(P<0.05);Gremlin-1、SUA及骨代谢指标联合对骨质疏松症诊断的曲线下面积为0.688,敏感度为92.53%、特异度为87.49%,显著高于单一指标诊断(P<0.05)。结论:Gremlin-1、SUA及骨代谢指标与骨质疏松病情严重程度具有密切关系,且联合诊断骨质疏松症敏感度及特异度较高。展开更多
基金This study was supported by the National Institutes of Health grant 1 R21 AA027014-01A1(T.C.K.)。
文摘Chronic pancreatitis(CP)is a major risk factor of pancreatic ductal adenocarcinoma(PDAC).How CP promotes pancreatic oncogenesis remains unclear.A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment,composed of activated fibroblasts and macrophages.Macrophages can be characterized as M1 or M2,with tumor-inhibiting or-promoting functions,respectively.We reported that Gremlin 1(GREM1),a key pro-fibrogenic factor,is upregulated in the stroma of CP.The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC.By mRNA in situ hybridization,we detected GREM1 mRNA expression withinα-smooth muscle actin(SMA)-positive fibroblasts of the pancreatic stroma.These designated FibroblastsGrem1+marginally increased from CP to pancreatic intraepithelial neoplasia(PanIN)and PDAC.Within PDAC,FibroblastsGrem1+increased with higher pathological tumor stages and in a majority of PDAC subtypes screened.Additionally,FibroblastsGrem1+positively correlated with total macrophages(MacCD68+)and M2 macrophages(M2CD163+)in PDAC.To begin exploring potential molecular links between FibroblastsGrem1+and macrophages in PDAC,we examined the expression of macrophage migration inhibitory factor(MIF),an endogenous counteracting molecule of GREM1 and an M1 macrophage promoting factor.By IHC staining of MIF,we found MIF to be expressed by tumor cells,positively correlated with GREM1;by IHC co-staining,we found MIF to be negatively correlated with M2CD163+expression.Our findings suggest that GREM1 expression by activated fibroblasts may promote PDAC development,and GREM1/MIF may play an important role in macrophage phenotype.
文摘目的了解妊娠中晚期孕妇血清Gremlin1水平变化,探究Gremlin1对妊娠期糖尿病(gestational diabetes mellitus,GDM)的影响。方法选取2020年9-11月就诊于安徽医科大学第一附属医院行孕期体检的妊娠24~28周并完善口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)的妊娠期女性175例为研究对象,根据OGTT结果分为GDM组和糖代谢正常组(NGT组)。收集两组临床资料,包括一般资料、Gremlin1水平及其他生化指标,比较两组临床资料的差异。结果GDM组妊娠前体重、妊娠后体重、妊娠前体质量指数(body mass index,BMI)、妊娠后BMI、空腹血糖(fasting blood glouse,FBG)、1 h血糖(1 h blood glouse,1 hBG)、2 h血糖(2 h blood glouse,2 hBG)、空腹胰岛素(fasting insulin,FINS)、1 h胰岛素(1 h insulin,1 hINS)、2 h胰岛素(2 h insulin,2 hINS)、空腹C肽(fasting C protein,FCP)、1 h C肽(1 h C protein,1 hCP)、2 h C肽(2 h C protein,2 hCP)、胰岛素抵抗指数(homeostatic model assessment insulin resistance,HOMA-IR)、血糖曲线下面积(AUC-G)、胰岛素曲线下面积(AUC-I)高于NGT组,胰岛β细胞功能指数(homeostatic model assessmentβcell insulin secretion index,HOMA-β)、胰岛素敏感指数(insulin sensitivity index,ISI)低于NGT组(均P<0.05)。GDM组血清Gremlin1水平高于NGT组(P<0.05)。Pearson相关分析提示血清Gremlin1水平与妊娠后BMI、FBG、1 hBG、1 hINS、2 hBG、2 hINS、2 hCP、HOMA-IR、AUG-G、AUC-I呈正相关,与HOMA-β、ISI呈负相关(均P<0.05)。多因素Logistic回归分析提示,血清Gremlin1是GDM的独立危险因素(OR=8.922,95%CI 1.863~42.736,P<0.05)。结论GDM患者血清Gremlin1升高,并与胰岛素抵抗呈正相关,参与GDM的糖代谢。
文摘目的:探讨Gremlin-1、血尿酸(SUA)及骨代谢指标表达水平与骨质疏松患者疾病严重程度的相关性及其联合诊断价值。方法:选取我院2019年1月到2020年12月收治的80例骨质疏松患者,对所有患者依照双X线吸收法诊断结果进行严重程度分组,将骨密度-2.5<T<-1患者分为骨量减少组(n=23),将骨密度T≤-2.5患者分为骨质疏松症组(n=37),将骨密度T≤-2.5,且发生过骨质疏松性骨折的患者分为严重骨质疏松症组(n=20)。对比三组患者Gremlin-1、SUA表达水平与骨代谢指标表达水平,采用Spearman相关分析Gremlin-1、SUA及骨代谢指标表达水平与骨质疏松患者疾病严重程度的相关性。最后建立ROC曲线,Gremlin-1、SUA及骨代谢指标联合对骨质疏松症的诊断价值。结果:三组患者Gremlin-1、SUA水平对比差异显著,骨量减少组Gremlin-1高于骨质疏松症组和严重骨质疏松症组,SUA低于骨质疏松症组和严重骨质疏松症组(P<0.05);三组患者维生素D3[25-(OD)-D3]、β-胶原特殊序列(β-CTX)、甲状旁腺激素(PTH)、I型前胶原N端肽(N-terminal peptide of type I procollagen,PINP)、骨钙素(OC)相关骨代谢指标水平对比差异显著,骨量减少组25-(OD)-D3、PINP、OC高于骨质疏松症组和严重骨质疏松症组,β-CTX、PTH低于骨质疏松症组和严重骨质疏松症组(P<0.05);SUA(r=-0.636)、β-CTX(r=00.626)、PTH(r=0.625)的表达与骨质疏松患者疾病严重程度呈正相关,Gremlin-1(r=-0.452)、25-(OD)-D3(r=-0.462)、PINP(r=-0.622)、OC(r=-0.426)的表达与骨质疏松患者疾病严重程度呈负相关(P<0.05);Gremlin-1、SUA及骨代谢指标联合对骨质疏松症诊断的曲线下面积为0.688,敏感度为92.53%、特异度为87.49%,显著高于单一指标诊断(P<0.05)。结论:Gremlin-1、SUA及骨代谢指标与骨质疏松病情严重程度具有密切关系,且联合诊断骨质疏松症敏感度及特异度较高。
