Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately m...Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).展开更多
目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT1...目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT10低表达患者比较,NAT10高表达患者预后较差(P<0.001)。Logistic回归分析结果表明,NAT10高表达与肝癌患者临床预后不良因素相关,NAT10高表达患者更易于进展到晚期。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,NAT10高表达样本中,异生物质代谢、凝血、脂肪酸代谢等相关基因特征均有差异富集。蛋白互作分析结果显示,NAT10可能与IGF2、SST、MUC2、CHGA、AGR2等基因存在相互作用。结论NAT10在肝癌中高表达,且表达水平与肝癌的临床特征及患者生存率存在相关性。NAT10可能是一种潜在的肝癌预后生物学标志物。展开更多
目的通过检测结核病患者药物代谢酶N-乙酰基转移酶2(N-acetyltransferase 2,NAT2)与妊娠X受体基因(Pregnane X receptor,PXR)启动子区rs3814055的基因多态性,根据结果进行风险分型,并验证对发生结核药物性肝损伤的预测价值。方法将382...目的通过检测结核病患者药物代谢酶N-乙酰基转移酶2(N-acetyltransferase 2,NAT2)与妊娠X受体基因(Pregnane X receptor,PXR)启动子区rs3814055的基因多态性,根据结果进行风险分型,并验证对发生结核药物性肝损伤的预测价值。方法将382例采用一线HREZ抗结核方案的敏感性结核患者在治疗前对NAT2及rs3814055的多态性位点进行测序分析,并进行风险分型,按结果分为高、中、低风险组,通过观察其实际发生肝损伤情况进行对比分析,以此验证风险类型与ATDILT间的相关性。结果低风险组患者185名,发生ATDILT的比例为15.7%(29/185);中风险组患者132名,发生ATDILT的比例为28.0%(37/132);高风险组患者65名,发生ATDILT的比例为32.3%(21/65)。高风险组与低风险组相比,发生肝损伤的相对危险度为1.909(95%CI为1.258~2.898);中风险组与低风险组相比,发生肝损伤的相对危险度为1.481(95%CI为1.135~1.933),且均有统计学意义(χ^(2)=8.316,P<0.01;χ^(2)=7.133,P<0.01)。高、中风险组间无显著性差异。结果显示患者性别与年龄对ATDILT发生率无显著性影响。结论基于NAT2及rs3814055多态性的联合检测的风险分型可用来预测结核病患者药物性肝损伤的发生。展开更多
旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样...旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样,采用荧光定量PCR分析VGLL2基因和其反义链转录本VGLL2-AS的表达谱;采用双向转录试验和核酸酶保护试验检测VGLL2和VGLL2-AS是否可以双向转录且两者之间关系;体外分离培养原代成肌细胞(11胚龄固始鸡胚),然后用2μg·mL^(-1)的放线菌素D处理成肌细胞(对照组不做处理),收取处理不同时间点细胞(0~8 h,每组各个时间点各做3个重复),检测VGLL2-AS与VGLL2的半衰期;分离鸡成肌细胞的细胞核和细胞质,通过RT-qPCR方法确定两者的细胞定位;利用PCR扩增及测序对VGLL2的转录本进行验证;最后利用RT-qPCR检测它们在固始蛋鸡胸肌组织(1日龄、6周龄、16周龄、22周龄、30周龄每个周龄各6只)中的时空表达规律和相关性。结果表明,VGLL2-AS在鸡的转录组中真实存在;VGLL2与VGLL2-AS均在肌肉中特异高表达(P<0.05);VGLL2-AS与VGLL2可以进行双向转录且二者之间可以形成双链RNA;VGLL2-AS半衰期较VGLL2长;在成肌细胞中,VGLL2-AS和VGLL2主要定位于细胞质中(P<0.001);VGLL2只存在VGLL2-mRNA、VGLL2-X2和VGLL2-X3转录本;VGLL2-mRNA和VGLL2-X3与VGLL2-AS表达趋势一致,且VGLL2-mRNA、X3和VGLL2-AS的表达呈现极强的正相关(r分别为0.943和0.935,P<0.01)。综上所述,VGLL2-AS作为VGLL2的反义链编码的lncRNA定位于细胞质中,可能通过与VGLL2形成的双链RNA之间的相互作用,然后参与调节VGLL2的表达并维持其稳定性,最终在鸡的早期肌肉发育中发挥重要作用。本研究的结果扩展了鸡中关于NATs的研究,并为鸡VGLL2基因与其天然反义链转录本VGLL2-AS在鸡骨骼肌发育中的生物学功能的研究奠定了基础,对于提高禽类的生长发育具有一定的意义。展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82573747,82172873,W2421095,and 82503888)National Science and Technology Major Project(Grant No.2025ZD0543900)+2 种基金Natural Science Foundation of Shandong Province(Grant Nos.ZR2024LMB011 and ZR2024QH058)Taishan Scholars Program of Shandong Province(Grant No.tsqn202211337)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003).
文摘Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).
文摘目的探讨NAT10在肝癌中的临床意义与潜在作用机制。方法基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)获得的50例正常和374例肿瘤样本,采用R 4.2.1处理所获数据。结果NAT10在肿瘤样本中的表达显著高于正常样本(P<0.001)。与NAT10低表达患者比较,NAT10高表达患者预后较差(P<0.001)。Logistic回归分析结果表明,NAT10高表达与肝癌患者临床预后不良因素相关,NAT10高表达患者更易于进展到晚期。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,NAT10高表达样本中,异生物质代谢、凝血、脂肪酸代谢等相关基因特征均有差异富集。蛋白互作分析结果显示,NAT10可能与IGF2、SST、MUC2、CHGA、AGR2等基因存在相互作用。结论NAT10在肝癌中高表达,且表达水平与肝癌的临床特征及患者生存率存在相关性。NAT10可能是一种潜在的肝癌预后生物学标志物。
文摘目的通过检测结核病患者药物代谢酶N-乙酰基转移酶2(N-acetyltransferase 2,NAT2)与妊娠X受体基因(Pregnane X receptor,PXR)启动子区rs3814055的基因多态性,根据结果进行风险分型,并验证对发生结核药物性肝损伤的预测价值。方法将382例采用一线HREZ抗结核方案的敏感性结核患者在治疗前对NAT2及rs3814055的多态性位点进行测序分析,并进行风险分型,按结果分为高、中、低风险组,通过观察其实际发生肝损伤情况进行对比分析,以此验证风险类型与ATDILT间的相关性。结果低风险组患者185名,发生ATDILT的比例为15.7%(29/185);中风险组患者132名,发生ATDILT的比例为28.0%(37/132);高风险组患者65名,发生ATDILT的比例为32.3%(21/65)。高风险组与低风险组相比,发生肝损伤的相对危险度为1.909(95%CI为1.258~2.898);中风险组与低风险组相比,发生肝损伤的相对危险度为1.481(95%CI为1.135~1.933),且均有统计学意义(χ^(2)=8.316,P<0.01;χ^(2)=7.133,P<0.01)。高、中风险组间无显著性差异。结果显示患者性别与年龄对ATDILT发生率无显著性影响。结论基于NAT2及rs3814055多态性的联合检测的风险分型可用来预测结核病患者药物性肝损伤的发生。
文摘旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样,采用荧光定量PCR分析VGLL2基因和其反义链转录本VGLL2-AS的表达谱;采用双向转录试验和核酸酶保护试验检测VGLL2和VGLL2-AS是否可以双向转录且两者之间关系;体外分离培养原代成肌细胞(11胚龄固始鸡胚),然后用2μg·mL^(-1)的放线菌素D处理成肌细胞(对照组不做处理),收取处理不同时间点细胞(0~8 h,每组各个时间点各做3个重复),检测VGLL2-AS与VGLL2的半衰期;分离鸡成肌细胞的细胞核和细胞质,通过RT-qPCR方法确定两者的细胞定位;利用PCR扩增及测序对VGLL2的转录本进行验证;最后利用RT-qPCR检测它们在固始蛋鸡胸肌组织(1日龄、6周龄、16周龄、22周龄、30周龄每个周龄各6只)中的时空表达规律和相关性。结果表明,VGLL2-AS在鸡的转录组中真实存在;VGLL2与VGLL2-AS均在肌肉中特异高表达(P<0.05);VGLL2-AS与VGLL2可以进行双向转录且二者之间可以形成双链RNA;VGLL2-AS半衰期较VGLL2长;在成肌细胞中,VGLL2-AS和VGLL2主要定位于细胞质中(P<0.001);VGLL2只存在VGLL2-mRNA、VGLL2-X2和VGLL2-X3转录本;VGLL2-mRNA和VGLL2-X3与VGLL2-AS表达趋势一致,且VGLL2-mRNA、X3和VGLL2-AS的表达呈现极强的正相关(r分别为0.943和0.935,P<0.01)。综上所述,VGLL2-AS作为VGLL2的反义链编码的lncRNA定位于细胞质中,可能通过与VGLL2形成的双链RNA之间的相互作用,然后参与调节VGLL2的表达并维持其稳定性,最终在鸡的早期肌肉发育中发挥重要作用。本研究的结果扩展了鸡中关于NATs的研究,并为鸡VGLL2基因与其天然反义链转录本VGLL2-AS在鸡骨骼肌发育中的生物学功能的研究奠定了基础,对于提高禽类的生长发育具有一定的意义。
