Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mech...Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.展开更多
目的探讨伴有骨髓水肿的老年膝骨关节炎与护骨因子、dickkopf-1(DKK-1)和硬骨素的相关性。方法选取2017年9月-2018年12月四川省骨科医院的老年膝骨关节炎患者100例,分为骨髓水肿组(50例)和非骨髓水肿组(50例),分别收集其基本资料、西安...目的探讨伴有骨髓水肿的老年膝骨关节炎与护骨因子、dickkopf-1(DKK-1)和硬骨素的相关性。方法选取2017年9月-2018年12月四川省骨科医院的老年膝骨关节炎患者100例,分为骨髓水肿组(50例)和非骨髓水肿组(50例),分别收集其基本资料、西安大略和麦克马斯特大学骨关节炎指数(Western Ontario and McMaster University Osteoarthritis Index,WOMAC)评分和视觉模拟评分法得分,检测其血清护骨因子、DKK-1、硬骨素、C反应蛋白、红细胞沉降率,并比较两组之间的差异,探讨其检测指标与骨髓水肿及其临床指标的相关性。结果两组患者的年龄、性别、病程、C反应蛋白和红细胞沉降率差异无统计学意义(P>0.05)。骨髓水肿组患者的WOMAC评分[(76.1±5.4)vs.(67.5±6.6)分]、视觉模拟评分法得分[(8.4±1.1)vs.(5.5±0.9)分]、滑膜炎比例(84.0%vs.52.0%)、护骨因子[(1.3±1.1)vs.(0.6±0.5)μg/L]、DKK-1[(18.4±16.9)vs.(6.9±6.0)μg/L]和硬骨素[(147.3±119.4)vs.(99.7±70.7)pg/mL]均高于非骨髓水肿组(P<0.05)。骨髓水肿组患者的骨髓水肿容积积分和程度积分与血清护骨因子相关性无统计学意义(P>0.05),与血清DKK-1(容积积分rs=0.464,P=0.001;程度积分rs=0.379,P=0.007)、硬骨素(容积积分rs=0.316,P=0.025;程度积分rs=0.461,P=0.003)呈正相关。结论伴有骨髓水肿的老年膝骨关节炎患者局部骨代谢指标护骨因子、DKK-1、硬骨素上调,尤以DKK-1、硬骨素与骨髓水肿的严重程度相关。展开更多
目的探讨玻璃酸钠+温针灸联合牛杞地黄丸剂治疗肝肾亏虚型膝骨关节炎老年患者的临床疗效。方法选取2022年2月—2023年6月期间四川省骨科医院风湿骨关节病科收治的肝肾亏虚型膝骨关节炎老年患者98例,按随机数字表法分为对照组和观察组,...目的探讨玻璃酸钠+温针灸联合牛杞地黄丸剂治疗肝肾亏虚型膝骨关节炎老年患者的临床疗效。方法选取2022年2月—2023年6月期间四川省骨科医院风湿骨关节病科收治的肝肾亏虚型膝骨关节炎老年患者98例,按随机数字表法分为对照组和观察组,每组各49例。对照组采用玻璃酸钠+温针灸理疗的方法。观察组在对照组患者治疗方法基础上加用牛杞地黄丸剂进行治疗。治疗5周后,观察比较两组患者临床疗效、不良反应情况,治疗前后膝关节视觉模拟评分(Visual analogue scale,VAS)、Lysholm膝关节评分、西安大略和麦克马斯特大学骨关节炎指数(Western ontario and mcmaster universities osteoarthritis index,WOMAC)评分、世界卫生组织生活质量评定简表(World health organization quality of life-brief,WHOQOL-BREF)评分。结果治疗后两组患者VAS评分均较治疗前降低,Lysholm评分均较治疗前升高,差异有统计学意义(P<0.05);且观察组VAS评分明显低于对照组,Lysholm评分明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者WOMAC评分均较治疗前降低,WHOQOL-BREF评分均较治疗前升高,差异有统计学意义(P<0.05),且观察组WOMAC评分明显低于对照组,WHOQOL-BREF评分明显高于对照组,差异有统计学意义(P<0.05)。治疗后观察组临床总有效率95.92%(47/49)明显高于对照组83.67%(41/49),差异有统计学意义(P<0.05)。治疗期间,两组患者各不良反应发生率比较,差异无统计学意义(P>0.05)。结论牛杞地黄丸剂可有效改善老年肝肾亏虚型膝骨关节炎患者疼痛程度,提高临床疗效及生活质量。展开更多
High-density genetic markers are required for genotyping and linkage mapping in identifying genes from crops with complex genomes, such as barley. As the most common variation, single nucleotide polymorphisms(SNPs) ar...High-density genetic markers are required for genotyping and linkage mapping in identifying genes from crops with complex genomes, such as barley. As the most common variation, single nucleotide polymorphisms(SNPs) are suitable for accurate genotyping by using the next-generation sequencing(NGS) technology. Reduced representation libraries(RRLs) of five barley accessions and one mutant were sequenced using NGS technology for SNP discovery. Twenty million short reads were generated and the proportion of repetitive sequences was reduced by more than 56%. A total of 6061 SNPs were identified, and 451 were mapped to the draft sequence of the barley genome with pairing reads. Eleven SNPs were validated using length polymorphic allele-specific PCR markers.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172840)Gusu Health Talents Project of Suzhou Municipal Health Commission(Grant Nos.GSWS2023007 and GSWS2022062)+2 种基金Suzhou Science and Technology Development Plan Project(Grant No.SYW2024005)Chinese Pharmaceutical Association Hospital Pharmacy Department(Grant No.CPA-Z05-ZC-2024002)Jiangsu Research Hospital Association for Precision Medication(Grant No.JY202202).
文摘Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.
文摘目的探讨伴有骨髓水肿的老年膝骨关节炎与护骨因子、dickkopf-1(DKK-1)和硬骨素的相关性。方法选取2017年9月-2018年12月四川省骨科医院的老年膝骨关节炎患者100例,分为骨髓水肿组(50例)和非骨髓水肿组(50例),分别收集其基本资料、西安大略和麦克马斯特大学骨关节炎指数(Western Ontario and McMaster University Osteoarthritis Index,WOMAC)评分和视觉模拟评分法得分,检测其血清护骨因子、DKK-1、硬骨素、C反应蛋白、红细胞沉降率,并比较两组之间的差异,探讨其检测指标与骨髓水肿及其临床指标的相关性。结果两组患者的年龄、性别、病程、C反应蛋白和红细胞沉降率差异无统计学意义(P>0.05)。骨髓水肿组患者的WOMAC评分[(76.1±5.4)vs.(67.5±6.6)分]、视觉模拟评分法得分[(8.4±1.1)vs.(5.5±0.9)分]、滑膜炎比例(84.0%vs.52.0%)、护骨因子[(1.3±1.1)vs.(0.6±0.5)μg/L]、DKK-1[(18.4±16.9)vs.(6.9±6.0)μg/L]和硬骨素[(147.3±119.4)vs.(99.7±70.7)pg/mL]均高于非骨髓水肿组(P<0.05)。骨髓水肿组患者的骨髓水肿容积积分和程度积分与血清护骨因子相关性无统计学意义(P>0.05),与血清DKK-1(容积积分rs=0.464,P=0.001;程度积分rs=0.379,P=0.007)、硬骨素(容积积分rs=0.316,P=0.025;程度积分rs=0.461,P=0.003)呈正相关。结论伴有骨髓水肿的老年膝骨关节炎患者局部骨代谢指标护骨因子、DKK-1、硬骨素上调,尤以DKK-1、硬骨素与骨髓水肿的严重程度相关。
文摘目的探讨玻璃酸钠+温针灸联合牛杞地黄丸剂治疗肝肾亏虚型膝骨关节炎老年患者的临床疗效。方法选取2022年2月—2023年6月期间四川省骨科医院风湿骨关节病科收治的肝肾亏虚型膝骨关节炎老年患者98例,按随机数字表法分为对照组和观察组,每组各49例。对照组采用玻璃酸钠+温针灸理疗的方法。观察组在对照组患者治疗方法基础上加用牛杞地黄丸剂进行治疗。治疗5周后,观察比较两组患者临床疗效、不良反应情况,治疗前后膝关节视觉模拟评分(Visual analogue scale,VAS)、Lysholm膝关节评分、西安大略和麦克马斯特大学骨关节炎指数(Western ontario and mcmaster universities osteoarthritis index,WOMAC)评分、世界卫生组织生活质量评定简表(World health organization quality of life-brief,WHOQOL-BREF)评分。结果治疗后两组患者VAS评分均较治疗前降低,Lysholm评分均较治疗前升高,差异有统计学意义(P<0.05);且观察组VAS评分明显低于对照组,Lysholm评分明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者WOMAC评分均较治疗前降低,WHOQOL-BREF评分均较治疗前升高,差异有统计学意义(P<0.05),且观察组WOMAC评分明显低于对照组,WHOQOL-BREF评分明显高于对照组,差异有统计学意义(P<0.05)。治疗后观察组临床总有效率95.92%(47/49)明显高于对照组83.67%(41/49),差异有统计学意义(P<0.05)。治疗期间,两组患者各不良反应发生率比较,差异无统计学意义(P>0.05)。结论牛杞地黄丸剂可有效改善老年肝肾亏虚型膝骨关节炎患者疼痛程度,提高临床疗效及生活质量。
基金supported by the National Natural Science Foundation of China (31000711, 31370032)China Agriculture Research System (CARS-05)the Agricultural Science and Technology Innovation Program
文摘High-density genetic markers are required for genotyping and linkage mapping in identifying genes from crops with complex genomes, such as barley. As the most common variation, single nucleotide polymorphisms(SNPs) are suitable for accurate genotyping by using the next-generation sequencing(NGS) technology. Reduced representation libraries(RRLs) of five barley accessions and one mutant were sequenced using NGS technology for SNP discovery. Twenty million short reads were generated and the proportion of repetitive sequences was reduced by more than 56%. A total of 6061 SNPs were identified, and 451 were mapped to the draft sequence of the barley genome with pairing reads. Eleven SNPs were validated using length polymorphic allele-specific PCR markers.
