BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres...BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.展开更多
目的构建过表达内质网应激标志蛋白葡萄糖调节蛋白78(Glucose-regulated protein 78,GRP78)的人乳腺癌细胞系HS578T、MDA-MB-231,为探讨GRP78在乳腺癌发生发展中的作用机制提供基础。方法采用分子克隆技术构建表达GRP78的慢病毒载体pCDH...目的构建过表达内质网应激标志蛋白葡萄糖调节蛋白78(Glucose-regulated protein 78,GRP78)的人乳腺癌细胞系HS578T、MDA-MB-231,为探讨GRP78在乳腺癌发生发展中的作用机制提供基础。方法采用分子克隆技术构建表达GRP78的慢病毒载体pCDH-CMV-GRP78-HA-EF1-Puro质粒,采用PCR法扩增质粒,后使用EcoRⅠ、NotⅠ限制性内切酶切割质粒,对酶切产物进行测序鉴定,成功构建pCDH-CMV-GRP78-HA-EF1-Puro质粒。取对数生长期293FT细胞系(克隆分离株),在培养皿中加入pCDH-CMV-GRP78-HA-EF1-Puro混合液,培养48 h收集含GRP78慢病毒颗粒的上清液,保存备用。另取对数生长期人乳腺癌细胞系HS578T及MDA-MB-231,置于含GRP78慢病毒颗粒上清液的培养基中培养,培养48 h时在培养基中加入1∶500稀释嘌呤霉素,筛选GRP78过表达的HS578T、MDA-MB-231细胞系。加入嘌呤霉素培养48 h采用Western Blotting法检测HS578T、MDA-MB-231细胞GRP78。采用激光共聚焦显微镜对HS578T、MDA-MB-231细胞中GRP78蛋白进行定位。结果构建表达GRP78的慢病毒载体pCDH-CMV-GRP78-HA-EF1-Puro质粒。GRP78过表达的HS578T、MDA-MB-231细胞系在78 kD左右可见明显GPR78蛋白电泳条带。HS578T细胞系中存在GRP78蛋白表达,主要分布在细胞质中。结论成功构建GRP78过表达的MDA-MB-231、HS578T细胞系,GRP78主要表达于细胞质中。展开更多
[Objective] The study was to understand the subcellular localization of OsWRKY78 protein in plants. [Method] Primers specific for OsWRKY78 gene were designed according to the OsWRKY78 full length sequence in Genbank. ...[Objective] The study was to understand the subcellular localization of OsWRKY78 protein in plants. [Method] Primers specific for OsWRKY78 gene were designed according to the OsWRKY78 full length sequence in Genbank. The gene was cloned by RT-PCR method. The gene was then recombined into a plasmid expression vector carrying green fluorescent protein (GFP) gene, pBinGFP. The recombinant was confirmed by PCR and enzyme digestion. The recombinant plasmid pBinGFP-OsWRKY was transformed into Arabidopsis through Agrobacterium tumefaciens strain GV3101 and transgenic plants were obtained. [Result] Measured by fluorescence microscopy, the expression of OsWRKY78 and GFP fusion protein in root tip cells was localized in the nucleus. [Conclusion] This study laid the foundation for further investigating the function of OsWRKY78 gene and its role in related signal transduction and provided theoretical basis for exploring the relation between OsWRKY78 gene and brown planthoppers.展开更多
AIM To investigate the protective effect of prostaglandin E1(PGE1) against endoplasmic reticulum(ER) stressinduced hepatocyte apoptosis, and to explore its underlying mechanisms.METHODS Thapsigargin(TG) was used to in...AIM To investigate the protective effect of prostaglandin E1(PGE1) against endoplasmic reticulum(ER) stressinduced hepatocyte apoptosis, and to explore its underlying mechanisms.METHODS Thapsigargin(TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinomaderived cell line Hep G2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RTPCR. Apoptotic index and cell viability of L02 cells and Hep G2 cells were determined with flow cytometry and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium] assay. RESULTS Pretreatment with 1 μmol/L PGE1 protected against TG-induced apoptosis in both L02 cells and Hep G2 cells. PGE1 enhanced the TG-induced expression of C/EBP homologous protein(CHOP), glucose-regulated protein(GRP) 78 and spliced X box-binding protein 1 at 6 h. However, it attenuated their expressions after 24 h. PGE1 alone induced protein and m RNA expressions of GRP78; PGE1 also induced protein expression of DNA damage-inducible gene 34 and inhibited the expressions of phospho-PKR-like ER kinase, phosphoeukaryotic initiation factor 2α and CHOP. Treatment with protein kinase A(PKA)-inhibitor H89 or KT5720 blocked PGE1-induced up-regulation of GRP78. Further, the cytoprotective effect of PGE1 on hepatocytes was not observed after blockade of GRP78 expression by H89 or small interfering RNA specifically targeted against human GRP78.CONCLUSION Our study demonstrates that PGE1 protects against ER stress-induced hepatocyte apoptosis via PKA pathwaydependent induction of GRP78 expression.展开更多
BACKGROUND: Glucose-regulated protein 78 (GRP78), a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein (CHOP), a transcription fact...BACKGROUND: Glucose-regulated protein 78 (GRP78), a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein (CHOP), a transcription factor specific for endoplasmic reticulum stress, can cause cell cycle arrest and cell apoptosis. OBJECTIVE: To study the protective effects of serum containing natural cerebrolysin on endoplasmic reticulum stress in tunicamycin-induced neuronal PC12 cells, and analyze the influence on GRP78 and CHOP expressions. DESIGN, TIME AND SETTING: A parallel controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, between March 2006 and August 2008. MATERIALS: Adult Sprague-Dawley rats were perfused with natural Cerebrolysin aqueous extract (0.185 g/kg/d) to produce serum containing natural Cerebrolysin. Physiological saline was used to produce blank serum. PC12 cell line was provided by Shanghai Institute of Cell Biology, Chinese Academy of Science. Tunicamycin was provided by Sigma (St. Louis, USA), and natural Cerebrolysin, containing ginseng, rhizoma gastrodiae, and gingko leaf (1:2:2), by Shengzhen Institute of Integrated Western and Traditional Chinese Medicine. METHODS: PC12 cells were treated with DMEM culture media containing 10% blank serum (normal control group), tunicamycin (1 μg/mL; model group), and 5%, 10%, and 15% serum containing natural cerebrolysin and tunicamycin (1 μ g/mL; low-, moderate-, and high-dose serum containing natural cerebrotysin groups), for 2 hours. MAIN OUTCOME MEASURES: PC12 cells were treated with tunicamycin for 48 hours after which apoptosis was measured using the TUNEL method to calculate apoptotic index. GRP78 expression was detected using immunocytochemistry. After 24 hours of treatment with tunicamycin, GRP78 and CHOP mRNA expressions were measured using RT-PCR. RESULTS: The apoptotic index and CHOP mRNA expression were in the model group and three cerebrolysin groups were significantly increased when compared to the normal control group (P 〈 0.05). In contrast, GRP78 mRNA and protein expressions were significantly decreased (P 〈 0.05). CONCLUSION: Serum containing natural cerebrolysin significantly reduced apoptosis in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress. These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.展开更多
Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n...Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.展开更多
目的探究维持性血液透析(maintenance hemodialysis,MHD)患者血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、骨形态发生蛋白2(bone morphogenetic protein 2,BMP2)水平及其与血管钙化(vascular calcification,VC)的相关...目的探究维持性血液透析(maintenance hemodialysis,MHD)患者血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、骨形态发生蛋白2(bone morphogenetic protein 2,BMP2)水平及其与血管钙化(vascular calcification,VC)的相关性。方法选取2020年4月~2022年5月三河燕郊福合第一医院收治的MHD患者为研究对象。收集临床资料,检测血清GRP78、BMP2水平并统计VC发生情况;分析MHD患者及VC患者血清GRP78、BMP2水平与一般临床资料的相关性,MHD患者发生VC的危险因素。结果共纳入112例患者,52例发生轻中度钙化(轻中度钙化组),21例发生重度钙化(重度钙化组),39例未发生钙化(无钙化组);无钙化组、轻中度钙化组、重度钙化组年龄、糖尿病比例、白蛋白(Alb)、血红蛋白(Hb)、血磷、血钙、钙磷乘积、全段甲状旁腺激素(iPTH)、血清GRP78、BMP2水平差异有统计学意义(F/χ^(2)=38.987、20.187、34.952、43.411、34.541、11.572、48.522、598.639、123.029、259.490,P均<0.001);MHD患者血清GRP78与BMP2水平呈正相关(r=0.490,P<0.001);VC患者血清GRP78与年龄、糖尿病、血磷、血钙、钙磷乘积、iPTH呈正相关(r=0.581、0.339、0.516、0.534、0.611、0.513,P均<0.001),与Alb、Hb呈负相关(r=-0.302、-0.296,P=0.005、0.007);VC患者血清BMP2与年龄、糖尿病、血磷、血钙、钙磷乘积、iPTH呈正相关(r=0.524、0.415、0.535、0.547、0.602、0.498,P均<0.001),与Alb、Hb呈负相关(r=-0.298、-0.284,P=0.008、0.011);年龄、钙磷乘积、iPTH、GRP78、BMP2为MHD患者发生VC的危险因素(OR值分别为3.009、4.321、4.719、6.679、6.237;95%CI分别为1.337~6.774、1.634~11.423、1.693~13.153、1.951~22.871、1.962~19.824;P值分别为0.008、0.003、0.003、0.002、0.002)。结论MHD患者血清GRP78、BMP2水平与VC的发生和病情有关,二者水平升高是VC发生的危险因素。展开更多
文摘BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.
文摘[Objective] The study was to understand the subcellular localization of OsWRKY78 protein in plants. [Method] Primers specific for OsWRKY78 gene were designed according to the OsWRKY78 full length sequence in Genbank. The gene was cloned by RT-PCR method. The gene was then recombined into a plasmid expression vector carrying green fluorescent protein (GFP) gene, pBinGFP. The recombinant was confirmed by PCR and enzyme digestion. The recombinant plasmid pBinGFP-OsWRKY was transformed into Arabidopsis through Agrobacterium tumefaciens strain GV3101 and transgenic plants were obtained. [Result] Measured by fluorescence microscopy, the expression of OsWRKY78 and GFP fusion protein in root tip cells was localized in the nucleus. [Conclusion] This study laid the foundation for further investigating the function of OsWRKY78 gene and its role in related signal transduction and provided theoretical basis for exploring the relation between OsWRKY78 gene and brown planthoppers.
基金Supported by the National Natural Science Foundation of China,No.81160067 and No.814600124
文摘AIM To investigate the protective effect of prostaglandin E1(PGE1) against endoplasmic reticulum(ER) stressinduced hepatocyte apoptosis, and to explore its underlying mechanisms.METHODS Thapsigargin(TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinomaderived cell line Hep G2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RTPCR. Apoptotic index and cell viability of L02 cells and Hep G2 cells were determined with flow cytometry and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium] assay. RESULTS Pretreatment with 1 μmol/L PGE1 protected against TG-induced apoptosis in both L02 cells and Hep G2 cells. PGE1 enhanced the TG-induced expression of C/EBP homologous protein(CHOP), glucose-regulated protein(GRP) 78 and spliced X box-binding protein 1 at 6 h. However, it attenuated their expressions after 24 h. PGE1 alone induced protein and m RNA expressions of GRP78; PGE1 also induced protein expression of DNA damage-inducible gene 34 and inhibited the expressions of phospho-PKR-like ER kinase, phosphoeukaryotic initiation factor 2α and CHOP. Treatment with protein kinase A(PKA)-inhibitor H89 or KT5720 blocked PGE1-induced up-regulation of GRP78. Further, the cytoprotective effect of PGE1 on hepatocytes was not observed after blockade of GRP78 expression by H89 or small interfering RNA specifically targeted against human GRP78.CONCLUSION Our study demonstrates that PGE1 protects against ER stress-induced hepatocyte apoptosis via PKA pathwaydependent induction of GRP78 expression.
基金Supported by:Scientific and Technological Foundation of the National Administration of Traditional Chinese Medicine of China,No.02-03LP41the Scientific and Technological Key Project of Guangdong Province,No. 2006B35630007
文摘BACKGROUND: Glucose-regulated protein 78 (GRP78), a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein (CHOP), a transcription factor specific for endoplasmic reticulum stress, can cause cell cycle arrest and cell apoptosis. OBJECTIVE: To study the protective effects of serum containing natural cerebrolysin on endoplasmic reticulum stress in tunicamycin-induced neuronal PC12 cells, and analyze the influence on GRP78 and CHOP expressions. DESIGN, TIME AND SETTING: A parallel controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, between March 2006 and August 2008. MATERIALS: Adult Sprague-Dawley rats were perfused with natural Cerebrolysin aqueous extract (0.185 g/kg/d) to produce serum containing natural Cerebrolysin. Physiological saline was used to produce blank serum. PC12 cell line was provided by Shanghai Institute of Cell Biology, Chinese Academy of Science. Tunicamycin was provided by Sigma (St. Louis, USA), and natural Cerebrolysin, containing ginseng, rhizoma gastrodiae, and gingko leaf (1:2:2), by Shengzhen Institute of Integrated Western and Traditional Chinese Medicine. METHODS: PC12 cells were treated with DMEM culture media containing 10% blank serum (normal control group), tunicamycin (1 μg/mL; model group), and 5%, 10%, and 15% serum containing natural cerebrolysin and tunicamycin (1 μ g/mL; low-, moderate-, and high-dose serum containing natural cerebrotysin groups), for 2 hours. MAIN OUTCOME MEASURES: PC12 cells were treated with tunicamycin for 48 hours after which apoptosis was measured using the TUNEL method to calculate apoptotic index. GRP78 expression was detected using immunocytochemistry. After 24 hours of treatment with tunicamycin, GRP78 and CHOP mRNA expressions were measured using RT-PCR. RESULTS: The apoptotic index and CHOP mRNA expression were in the model group and three cerebrolysin groups were significantly increased when compared to the normal control group (P 〈 0.05). In contrast, GRP78 mRNA and protein expressions were significantly decreased (P 〈 0.05). CONCLUSION: Serum containing natural cerebrolysin significantly reduced apoptosis in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress. These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.
基金supported by grants from the National Natural Science Foundation of China(No.81360185)the Foundation of the First Affiliated Hospital of Medical College of Shihezi University of China(No.SS2011-095)
文摘Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.
文摘目的探究维持性血液透析(maintenance hemodialysis,MHD)患者血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、骨形态发生蛋白2(bone morphogenetic protein 2,BMP2)水平及其与血管钙化(vascular calcification,VC)的相关性。方法选取2020年4月~2022年5月三河燕郊福合第一医院收治的MHD患者为研究对象。收集临床资料,检测血清GRP78、BMP2水平并统计VC发生情况;分析MHD患者及VC患者血清GRP78、BMP2水平与一般临床资料的相关性,MHD患者发生VC的危险因素。结果共纳入112例患者,52例发生轻中度钙化(轻中度钙化组),21例发生重度钙化(重度钙化组),39例未发生钙化(无钙化组);无钙化组、轻中度钙化组、重度钙化组年龄、糖尿病比例、白蛋白(Alb)、血红蛋白(Hb)、血磷、血钙、钙磷乘积、全段甲状旁腺激素(iPTH)、血清GRP78、BMP2水平差异有统计学意义(F/χ^(2)=38.987、20.187、34.952、43.411、34.541、11.572、48.522、598.639、123.029、259.490,P均<0.001);MHD患者血清GRP78与BMP2水平呈正相关(r=0.490,P<0.001);VC患者血清GRP78与年龄、糖尿病、血磷、血钙、钙磷乘积、iPTH呈正相关(r=0.581、0.339、0.516、0.534、0.611、0.513,P均<0.001),与Alb、Hb呈负相关(r=-0.302、-0.296,P=0.005、0.007);VC患者血清BMP2与年龄、糖尿病、血磷、血钙、钙磷乘积、iPTH呈正相关(r=0.524、0.415、0.535、0.547、0.602、0.498,P均<0.001),与Alb、Hb呈负相关(r=-0.298、-0.284,P=0.008、0.011);年龄、钙磷乘积、iPTH、GRP78、BMP2为MHD患者发生VC的危险因素(OR值分别为3.009、4.321、4.719、6.679、6.237;95%CI分别为1.337~6.774、1.634~11.423、1.693~13.153、1.951~22.871、1.962~19.824;P值分别为0.008、0.003、0.003、0.002、0.002)。结论MHD患者血清GRP78、BMP2水平与VC的发生和病情有关,二者水平升高是VC发生的危险因素。