目的分析早期2型糖尿病肾病患者应用补肾活血泄浊汤治疗的临床效果。方法选取2019年1月—2022年12月江苏武进中医院收治的早期2型糖尿病肾病患者79例,随机数字表法分为对照组(39例)和研究组(40例)。对照组采用西医常规治疗,研究组在对...目的分析早期2型糖尿病肾病患者应用补肾活血泄浊汤治疗的临床效果。方法选取2019年1月—2022年12月江苏武进中医院收治的早期2型糖尿病肾病患者79例,随机数字表法分为对照组(39例)和研究组(40例)。对照组采用西医常规治疗,研究组在对照组的基础上采用补肾活血泄浊汤治疗,两组连续治疗4周。比较治疗4周后两组临床疗效及治疗期间不良反应发生情况,治疗前及治疗4周后中医证候积分、24 h尿蛋白(24 h urinary protein,24 h pro)、24 h尿白蛋白的排泄率(24 h urinary albumin excretion rate,UAER)、血清单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、β2-微球蛋白(β2-microglobulin,β2-MG)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、白细胞介素-17(interleukin-17,IL-17)、可溶性细胞间黏附分子(soluble intercellular adhesion molecule,sICAM-1)水平。结果治疗4周后,研究组总有效率高于对照组;与治疗前比较,治疗4周后两组24 h pro、UAER、血清β2-MG、TGF-β1、MCP-1、sICAM-1、IL-17水平、中医证候各项积分降低,且研究组水平更低(P<0.05)。结论早期2型糖尿病肾病患者应用补肾活血泄浊汤治疗,有助于提高临床疗效,缓解临床症状、体征,改善肾功能,下调炎症因子指标(血清TGF-β1、MCP-1、sICAM-1、IL-17)表达水平,且不良反应少。展开更多
Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory r...Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory response and phagocytic functions,which contributes to the progression of NP.Most current research on NP focuses on microglial inflammation,with relatively little attention to their phagocytic function.Early growth response factor 2(EGR2)has been shown to regulate microglial phagocytosis,but its specific role in NP remains unclear.This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP,with the goal of identifying potential therapeutic targets.Methods:Adult male Sprague-Dawley(SD)rats were used to establish a chronic constriction injury(CCI)model of the sciatic nerve.Pain behaviors were assessed on days 1,3,7,10,and 14 post-surgery to confirm successful model induction.The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR(RT-qPCR),Western blotting,and immunofluorescence staining.Adeno-associated virus(AAV)was used to overexpress EGR2 in the spinal cord,and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP.CCI and lipopolysaccharide(LPS)models were established in animals and microglial cell lines,respectively,and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays.After confirming the involvement of microglial phagocytosis in NP,AAV was used to overexpress EGR2 in both in vivo and in vitro models,and phagocytic activity was further evaluated.Finally,eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses to identify potential downstream effectors of EGR2.Results:The CCI model successfully induced NP.Following CCI,EGR2 expression in the spinal cord was upregulated in parallel with NP development.Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats.Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis,which was further amplified by EGR2 overexpression.Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation.Among them,Lag3 emerged as a potential downstream target of EGR2.Conclusion:EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.展开更多
抗体药物偶联物(antibody drug conjugates,ADCs)是一类新型的抗肿瘤药物,兼具有靶向药物的特异性和化疗药物的高度抗肿瘤活性,极具临床应用前景。近年来,乳腺癌的治疗正进入ADCs治疗时代,以恩美曲妥珠单抗、德曲妥珠单抗等为代表的ADCs...抗体药物偶联物(antibody drug conjugates,ADCs)是一类新型的抗肿瘤药物,兼具有靶向药物的特异性和化疗药物的高度抗肿瘤活性,极具临床应用前景。近年来,乳腺癌的治疗正进入ADCs治疗时代,以恩美曲妥珠单抗、德曲妥珠单抗等为代表的ADCs,为人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性乳腺癌患者的治疗带来了新的突破。此外,ADCs的出现,引入了“HER2低表达(HER2-low)”的概念,并为HER2-low的乳腺癌患者带来了生存获益。本综述重点探讨了ADCs在治疗HER2表达乳腺癌中的应用进展。展开更多
文摘目的分析早期2型糖尿病肾病患者应用补肾活血泄浊汤治疗的临床效果。方法选取2019年1月—2022年12月江苏武进中医院收治的早期2型糖尿病肾病患者79例,随机数字表法分为对照组(39例)和研究组(40例)。对照组采用西医常规治疗,研究组在对照组的基础上采用补肾活血泄浊汤治疗,两组连续治疗4周。比较治疗4周后两组临床疗效及治疗期间不良反应发生情况,治疗前及治疗4周后中医证候积分、24 h尿蛋白(24 h urinary protein,24 h pro)、24 h尿白蛋白的排泄率(24 h urinary albumin excretion rate,UAER)、血清单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、β2-微球蛋白(β2-microglobulin,β2-MG)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、白细胞介素-17(interleukin-17,IL-17)、可溶性细胞间黏附分子(soluble intercellular adhesion molecule,sICAM-1)水平。结果治疗4周后,研究组总有效率高于对照组;与治疗前比较,治疗4周后两组24 h pro、UAER、血清β2-MG、TGF-β1、MCP-1、sICAM-1、IL-17水平、中医证候各项积分降低,且研究组水平更低(P<0.05)。结论早期2型糖尿病肾病患者应用补肾活血泄浊汤治疗,有助于提高临床疗效,缓解临床症状、体征,改善肾功能,下调炎症因子指标(血清TGF-β1、MCP-1、sICAM-1、IL-17)表达水平,且不良反应少。
基金supported by the National Natural Science Foundation of China(82071249 and 81771207).
文摘Objective:Neuropathic pain(NP)is one of the most common forms of chronic pain,yet current treatment options are limited in effectiveness.Peripheral nerve injury activates spinal microglia,altering their inflammatory response and phagocytic functions,which contributes to the progression of NP.Most current research on NP focuses on microglial inflammation,with relatively little attention to their phagocytic function.Early growth response factor 2(EGR2)has been shown to regulate microglial phagocytosis,but its specific role in NP remains unclear.This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP,with the goal of identifying potential therapeutic targets.Methods:Adult male Sprague-Dawley(SD)rats were used to establish a chronic constriction injury(CCI)model of the sciatic nerve.Pain behaviors were assessed on days 1,3,7,10,and 14 post-surgery to confirm successful model induction.The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR(RT-qPCR),Western blotting,and immunofluorescence staining.Adeno-associated virus(AAV)was used to overexpress EGR2 in the spinal cord,and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP.CCI and lipopolysaccharide(LPS)models were established in animals and microglial cell lines,respectively,and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays.After confirming the involvement of microglial phagocytosis in NP,AAV was used to overexpress EGR2 in both in vivo and in vitro models,and phagocytic activity was further evaluated.Finally,eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses to identify potential downstream effectors of EGR2.Results:The CCI model successfully induced NP.Following CCI,EGR2 expression in the spinal cord was upregulated in parallel with NP development.Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats.Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis,which was further amplified by EGR2 overexpression.Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation.Among them,Lag3 emerged as a potential downstream target of EGR2.Conclusion:EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
