Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whethe...Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whether its therapeutic mechanism is related to the expression of HIF-1α and VEGF (angiogenic factors), BMP2 and Osterix (osteogenic factor), CD31 (type H vascular marker) and MMP13 (bone destruction-related factor). Methods: Twenty-seven healthy male New Zealand white rabbits were divided into a normal group, model group, traditional Chinese medcine (TCM) group (clinical equivalent dose group of YKP), miR-130a inhibitor group and TCM + inhibitor group. The SANFH model was established by combining horse serum with methylprednisolone. After the model is successfully established, TCM group was given 6.44 g/kg·d YKP by gavage, and the miR-130a gene inhibitor group was intraperitoneally injected with 25 mg/kg miR-130a inhibitor, locked nucleic acid (LNA)-anti-miR-130a. TCM + inhibitor group was treated with YKP intragastrically and miR-130a inhibitor intraperitoneally. The rabbits in the normal group and the model group were intragastrically administered with normal saline 10 ml/d. Once a day for 4 weeks. The avascular necrosis was detected by HE staining. The contents of HIF-1α, VEGF, BMP2 and Osterix in rabbit tissues were detected by qRT-PCR kit, and the expression of CD31 and MMP13 was detected by immunofluorescence staining. Results: In the normal group, the surface of the cartilage layer of the femoral head was smooth, the bone trabeculae were intact and densely arranged, the cells of each layer were neatly arranged, the morphology of the bone cells, the chondrocytes and the adipocytes were normal. In the model group, cartilage surfaces of the femoral head showed exfoliative cracks. The bone trabecular structure was loose and incomplete, chondrocytes, osteoblasts and bone marrow cells were significantly reduced, and the number of empty bone traps was significantly increased. In the TCM-treated group, more chondrocytes, thicker cartilage layer, and more regular bone trabeculae were detected as compared to model rabbits. In contrast, the cartilage layer was thinner, the destruction and fracture of bone trabeculae was more serious, chondrocytes and osteocytes were decreased as compared to model group. The expression of HIF-1α, VEGF, BMP2, and Osterix in the model group decreased significantly as compared to the normal group (P Conclusion: YKP can regulate the expression of angiogenic-related factors (VEGF and HIF-α), osteogenic-related factors (BMP2 and Osterix), and H-type vascular marker CD31, resulting in increased expressions of VEGF, HIF-α, BMP2, and Osterix, which promote intra-femoral head revascularization. Meanwhile, YKP decreased the expression of bone-destruction-related factor MMP13, thus enhancing the ability of bone tissue to repair itself. Regulation of these molecules’ expression may be one of the mechanisms of YKP in the treatment of hormonal femoral head necrosis.展开更多
Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphism...Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.展开更多
Objective： To observe the regulation of Youguiyin （YGY, 右归钦） on the gene expression profile of the rat with steroid-induced femoral head necrosis （sFHN）, for the sake of investigating its molecular mechanism o...Objective： To observe the regulation of Youguiyin （YGY, 右归钦） on the gene expression profile of the rat with steroid-induced femoral head necrosis （sFHN）, for the sake of investigating its molecular mechanism of sFHN prevention and treatment. Methods： All the 30 rats were randomly divided into three groups, the normal control group （A）, the model control group （B）, and the YGY treated group （C）, 10 in each group. After rats in Groups B and C were being made into FHN models with steroid injection, they received a daily intragastdc administration of saline and YGY respectively in equal volume for a total of 6 weeks, while to the unmodeled normal rats in Group A, saline was administered instead. The rats were sacrificed at the terminal of administration; their mRNA from femoral head tissue was extracted and prepared to cDNA probe through inverse transcription for detecting gene expression profile by microarray, outcomes of which was passing fluorescence quantitative PCR verification, and the differential expressed genes were analyzed adopting gene ontology （GO） method. Results： Compared with Group A, the numbers of differential genes found in Groups B and C were 190 and 92, respectively, but the changing trend in the two groups was opposite, mainly manifested as down-regulating in Group B/Group A （GB/GA） and up-regulating in Group C/Group B （GC/GB）. The analysis showed that these differential genes were mainly assigned to cell apoptosis, signal transduction, metabolism, cell proliferation and differentiation, cell cycle, blood coagulation, antioxidant activity, etc. Conclusions： sFHN was regulated by various genes; the regulation of YGY on expressions of these genes and the intra]extra-cellular signaling processes was possibly the molecular mechanism of YGY for preventing/treating sFHN. This study gave an explanation to the effectiveness of Chinese medicine in preventing/treating FHN from aspects of gene expression and enriched the Chinese medicine theory of ＂Kidney （Shen） governing bones＂.展开更多
激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SIONFH)是由于糖皮质激素使用不当或过度而引起的髋关节疾病,发病机制尚未统一,临床疗效亦不佳。当前,没有效果明确的药物可以延缓疾病进程,而中医药治疗SIONFH在...激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SIONFH)是由于糖皮质激素使用不当或过度而引起的髋关节疾病,发病机制尚未统一,临床疗效亦不佳。当前,没有效果明确的药物可以延缓疾病进程,而中医药治疗SIONFH在临床上取得一定疗效。即便如此,仍未能完整的从分子生物及细胞生物学角度阐明中药治疗SIONFH的作用机制。转化生长因子-β(TGF-β)/骨形态发生蛋白(BMP)/Smad信号通路的转导是防治SIONFH的研究热点之一,故该文阐明了该信号通路的转导机制以及与SIONFH的联系,检索了基于该通路治疗SIONFH的全部中药及复方并阐述其影响机制。基于中医对SIONFH的认识,现临床上使用补肝肾强筋骨以及活血祛瘀通络类的方药治疗SIONFH,且具有良好的疗效。中药通过调控该通路,可刺激骨髓间充质干细胞成骨分化,降低破骨细胞含量,减少脂肪生成,改善微循环,抗氧化损伤,促进股骨头内血管新生,从而促进股骨头损伤的修复。现基于TGF-β/BMP/Smad信号通路对中医药治疗SIONFH的研究进展做一综述,期许为中医药治疗SIONFH提供理论依据及参考。展开更多
激素性股骨头坏死(steroid-induced necrosis of the femoral head, SNOFH)是骨科常见难治性疾病,又被视为“不死癌症”,若不及时干预将导致患者面临人工全髋关节置换术的风险。近些年研究证实,“成骨-成血管耦联”途径研究SNOFH发生发...激素性股骨头坏死(steroid-induced necrosis of the femoral head, SNOFH)是骨科常见难治性疾病,又被视为“不死癌症”,若不及时干预将导致患者面临人工全髋关节置换术的风险。近些年研究证实,“成骨-成血管耦联”途径研究SNOFH发生发展的机制具有重要意义。SNOFH中医病机责之于脾肾亏虚为本,瘀血为病,痰阻为渐,毒聚为损。“成骨-成血管耦联”机制与“瘀去-新生-骨合”中医理论存在高度契合性。越来越多的临床证据表明中医药治疗SNOFH不仅具有疗效显著、不良反应小、价格低廉等优势,还能提高患者生存质量,为促进股骨头血管重建与再生以及股骨头坏死骨修复等发挥重要作用。基于“瘀去-新生-骨合”理论,临床上多采用补肾活血类中药及中药复方用于SNOFH防治,运用“成骨”之健脾补肾药,“成血管”之活血化瘀药,祛除“抑制因素”之化痰药、祛湿药,有步骤、有层次的治疗SNOFH取得显著效果。因此,从“成骨-成血管耦联”角度探讨SNOFH中医药干预的科学内涵已成为当今研究新热点,能够为后续SNOFH的防治研究和新药研发提供理论参考和借鉴。展开更多
文摘Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whether its therapeutic mechanism is related to the expression of HIF-1α and VEGF (angiogenic factors), BMP2 and Osterix (osteogenic factor), CD31 (type H vascular marker) and MMP13 (bone destruction-related factor). Methods: Twenty-seven healthy male New Zealand white rabbits were divided into a normal group, model group, traditional Chinese medcine (TCM) group (clinical equivalent dose group of YKP), miR-130a inhibitor group and TCM + inhibitor group. The SANFH model was established by combining horse serum with methylprednisolone. After the model is successfully established, TCM group was given 6.44 g/kg·d YKP by gavage, and the miR-130a gene inhibitor group was intraperitoneally injected with 25 mg/kg miR-130a inhibitor, locked nucleic acid (LNA)-anti-miR-130a. TCM + inhibitor group was treated with YKP intragastrically and miR-130a inhibitor intraperitoneally. The rabbits in the normal group and the model group were intragastrically administered with normal saline 10 ml/d. Once a day for 4 weeks. The avascular necrosis was detected by HE staining. The contents of HIF-1α, VEGF, BMP2 and Osterix in rabbit tissues were detected by qRT-PCR kit, and the expression of CD31 and MMP13 was detected by immunofluorescence staining. Results: In the normal group, the surface of the cartilage layer of the femoral head was smooth, the bone trabeculae were intact and densely arranged, the cells of each layer were neatly arranged, the morphology of the bone cells, the chondrocytes and the adipocytes were normal. In the model group, cartilage surfaces of the femoral head showed exfoliative cracks. The bone trabecular structure was loose and incomplete, chondrocytes, osteoblasts and bone marrow cells were significantly reduced, and the number of empty bone traps was significantly increased. In the TCM-treated group, more chondrocytes, thicker cartilage layer, and more regular bone trabeculae were detected as compared to model rabbits. In contrast, the cartilage layer was thinner, the destruction and fracture of bone trabeculae was more serious, chondrocytes and osteocytes were decreased as compared to model group. The expression of HIF-1α, VEGF, BMP2, and Osterix in the model group decreased significantly as compared to the normal group (P Conclusion: YKP can regulate the expression of angiogenic-related factors (VEGF and HIF-α), osteogenic-related factors (BMP2 and Osterix), and H-type vascular marker CD31, resulting in increased expressions of VEGF, HIF-α, BMP2, and Osterix, which promote intra-femoral head revascularization. Meanwhile, YKP decreased the expression of bone-destruction-related factor MMP13, thus enhancing the ability of bone tissue to repair itself. Regulation of these molecules’ expression may be one of the mechanisms of YKP in the treatment of hormonal femoral head necrosis.
基金supported by the General Project of Henan Natural Science Foundation(No.232300420034)the National Natural Science Foundation of China for the Youth(No.81600555)the General Project of China Postdoctoral Science Foundation(No.2018M640684)。
文摘Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.
基金Supported by the National Natural Science Foundation of China (No.30672702,No.81072820 and No.30873276)Key Program of Traditional Chinese Medicine of Zhejiang Province (No.2005Z003)
文摘Objective： To observe the regulation of Youguiyin （YGY, 右归钦） on the gene expression profile of the rat with steroid-induced femoral head necrosis （sFHN）, for the sake of investigating its molecular mechanism of sFHN prevention and treatment. Methods： All the 30 rats were randomly divided into three groups, the normal control group （A）, the model control group （B）, and the YGY treated group （C）, 10 in each group. After rats in Groups B and C were being made into FHN models with steroid injection, they received a daily intragastdc administration of saline and YGY respectively in equal volume for a total of 6 weeks, while to the unmodeled normal rats in Group A, saline was administered instead. The rats were sacrificed at the terminal of administration; their mRNA from femoral head tissue was extracted and prepared to cDNA probe through inverse transcription for detecting gene expression profile by microarray, outcomes of which was passing fluorescence quantitative PCR verification, and the differential expressed genes were analyzed adopting gene ontology （GO） method. Results： Compared with Group A, the numbers of differential genes found in Groups B and C were 190 and 92, respectively, but the changing trend in the two groups was opposite, mainly manifested as down-regulating in Group B/Group A （GB/GA） and up-regulating in Group C/Group B （GC/GB）. The analysis showed that these differential genes were mainly assigned to cell apoptosis, signal transduction, metabolism, cell proliferation and differentiation, cell cycle, blood coagulation, antioxidant activity, etc. Conclusions： sFHN was regulated by various genes; the regulation of YGY on expressions of these genes and the intra]extra-cellular signaling processes was possibly the molecular mechanism of YGY for preventing/treating sFHN. This study gave an explanation to the effectiveness of Chinese medicine in preventing/treating FHN from aspects of gene expression and enriched the Chinese medicine theory of ＂Kidney （Shen） governing bones＂.
文摘激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SIONFH)是由于糖皮质激素使用不当或过度而引起的髋关节疾病,发病机制尚未统一,临床疗效亦不佳。当前,没有效果明确的药物可以延缓疾病进程,而中医药治疗SIONFH在临床上取得一定疗效。即便如此,仍未能完整的从分子生物及细胞生物学角度阐明中药治疗SIONFH的作用机制。转化生长因子-β(TGF-β)/骨形态发生蛋白(BMP)/Smad信号通路的转导是防治SIONFH的研究热点之一,故该文阐明了该信号通路的转导机制以及与SIONFH的联系,检索了基于该通路治疗SIONFH的全部中药及复方并阐述其影响机制。基于中医对SIONFH的认识,现临床上使用补肝肾强筋骨以及活血祛瘀通络类的方药治疗SIONFH,且具有良好的疗效。中药通过调控该通路,可刺激骨髓间充质干细胞成骨分化,降低破骨细胞含量,减少脂肪生成,改善微循环,抗氧化损伤,促进股骨头内血管新生,从而促进股骨头损伤的修复。现基于TGF-β/BMP/Smad信号通路对中医药治疗SIONFH的研究进展做一综述,期许为中医药治疗SIONFH提供理论依据及参考。
文摘激素性股骨头坏死(steroid-induced necrosis of the femoral head, SNOFH)是骨科常见难治性疾病,又被视为“不死癌症”,若不及时干预将导致患者面临人工全髋关节置换术的风险。近些年研究证实,“成骨-成血管耦联”途径研究SNOFH发生发展的机制具有重要意义。SNOFH中医病机责之于脾肾亏虚为本,瘀血为病,痰阻为渐,毒聚为损。“成骨-成血管耦联”机制与“瘀去-新生-骨合”中医理论存在高度契合性。越来越多的临床证据表明中医药治疗SNOFH不仅具有疗效显著、不良反应小、价格低廉等优势,还能提高患者生存质量,为促进股骨头血管重建与再生以及股骨头坏死骨修复等发挥重要作用。基于“瘀去-新生-骨合”理论,临床上多采用补肾活血类中药及中药复方用于SNOFH防治,运用“成骨”之健脾补肾药,“成血管”之活血化瘀药,祛除“抑制因素”之化痰药、祛湿药,有步骤、有层次的治疗SNOFH取得显著效果。因此,从“成骨-成血管耦联”角度探讨SNOFH中医药干预的科学内涵已成为当今研究新热点,能够为后续SNOFH的防治研究和新药研发提供理论参考和借鉴。
