目的探讨超声造影定性及定量参数与乳腺癌患者新辅助化疗疗效及CBL proto-oncogene家族蛋白成员CBL原癌基因C(CBL proto-oncogene C,CBLC)蛋白、X型胶原蛋白(type X collagen,COL10)成员COL10A1表达水平的相关性。方法选取2019年6月至2...目的探讨超声造影定性及定量参数与乳腺癌患者新辅助化疗疗效及CBL proto-oncogene家族蛋白成员CBL原癌基因C(CBL proto-oncogene C,CBLC)蛋白、X型胶原蛋白(type X collagen,COL10)成员COL10A1表达水平的相关性。方法选取2019年6月至2021年6月于新疆医科大学第二附属医院接受全程新辅助化疗并进行保乳或全乳切除术治疗的192例乳腺癌患者作为研究对象,术中取乳腺癌组织和癌旁正常组织。化疗前,采用飞利浦iU22彩色多普勒超声诊断仪对病灶进行检查,观察并记录定性和定量参数。新辅助化疗结束后行肿块切除术,由2位病理学副主任及以上医师依据Miller and Payne改良病理反应分级标准评估疗效,分为病理完全应答(pathological complete response,PCR)组(102例)和非PCR组(90例);采用免疫组织化学法检测组织中的CBLC、COL10A1表达水平。结果单因素分析结果表明,非PCR组的增强边界不清晰、出现灌注缺损、周围放射状增强和增强不均匀的比例显著高于PCR组,非PCR组的峰值强度(peak intensity,PI)和曲线下面积(area under curve,AUC)均显著高于PCR组(均P<0.05);CBLC高表达者出现高增强、增强边界不清晰、灌注缺损、增强不均匀的比例显著低于低表达者,PI和AUC均显著低于低表达者(均P<0.05);COL10A1高表达者出现高增强、周围放射状增强、增强不均匀的比例显著高于低表达者,PI和AUC均显著高于低表达者,而达峰时间(time to peak,TTP)显著低于低表达者(均P<0.05)。多因素Logistic回归分析结果显示,增强边界不清晰、PI及AUC增大是出现非PCR的独立危险因素(均P<0.05);高增强、增强边界不清晰、PI及AUC增大是CBLC低表达的独立危险因素(均P<0.05);高增强、PI增大及TTP减小是COL10A1高表达的独立危险因素(均P<0.05)。结论超声造影定性及定量参数可用于预测乳腺癌患者新辅助化疗疗效及CBLC、COL10A1表达水平,有助于选择治疗方案和预测患者预后。展开更多
Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese ca...Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese cases with CblC disease.Methods We carried out a national,retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G>A variant either in a homozygous or compound heterozygous state.The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G>A mutation.Clinical features,including disease onset,symptoms,biochemical metabolites,gene mutation,and follow-up outcomes were reviewed and analyzed in detail.The median follow-up period spanned 3 years and 8 months,with a range of 1 year and 2 months to 12 years and 10 months.Results Among 195 patients carrying the c.482G>A variant,125(64.1%)cases were diagnosed by newborn screening(NBS),60(30.8%)cases were detected due to disease onset,and 10(5.1%)cases were identified from sibling diagnoses.One hundred and seventeen(93.6%)individuals who were diagnosed by NBS,and nine patients who came from sibling diagnoses remained asymptomatic in this study.From 69 symptomatic patients of the c.482G>A group,more patients presented with later onset,and the top six common clinical symptoms at disease onset were developmental delay(59.4%),lower limb weakness and poor exercise tolerance(50.7%),cognitive decline(37.7%),gait instability and abnormal posture(36.2%),seizures(26.1%),and psychiatric and behavioral disturbances(24.6%).In the 159 symptomatic patients lacking c.482G>A variants,the most frequently observed clinical manifestations at disease onset included developmental delay(81.8%),lethargy and feeding difficulty(62.9%),lower limb weakness and poor exercise tolerance(54.7%),prolonged neonatal jaundice(51.6%),vomiting(47.2%),and seizures(32.7%).Before treatment,the levels of blood propionylcarnitine,propionylcarnitine/acetylcarnitine ratio,and homocysteine in the c.482G>A group were significantly lower(P<0.05)than those in the non-c.482G>A group,while the concentration of urinary methylmalonic acid was slightly lower(P>0.05).The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels(P<0.05).In patients carrying the c.482G>A variant compared with the non-c.428G>A group,there were markedly lower rates of mortality(0.5%vs.2.0%)and developmental delay(20.5%vs.65.5%).When compared with individuals diagnosed due to disease onset,those identified through NBS in either group exhibited a reduced proportion of disease onset(6.7%vs.100%in the c.482G>A group,54.4%vs.100%in the non-c.482G>A group),lower mortality(0.0%vs.1.7%in the c.482G>A group,0.0%vs.3.6%in the non-c.482G>A group),and had a higher percentage of patients exhibiting normal psychomotor and language development(99.3%vs.33.3%in the c.482G>A group,58.9%vs.10.9%in the non-c.482G>A group).Conclusions The c.482G>A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease.Patients with this mutation tend to have a relatively better response to hydroxocobalamin,better metabolic control,and more favorable neurological outcomes.NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis,resulting in favorable clinical outcomes.展开更多
文摘目的探讨超声造影定性及定量参数与乳腺癌患者新辅助化疗疗效及CBL proto-oncogene家族蛋白成员CBL原癌基因C(CBL proto-oncogene C,CBLC)蛋白、X型胶原蛋白(type X collagen,COL10)成员COL10A1表达水平的相关性。方法选取2019年6月至2021年6月于新疆医科大学第二附属医院接受全程新辅助化疗并进行保乳或全乳切除术治疗的192例乳腺癌患者作为研究对象,术中取乳腺癌组织和癌旁正常组织。化疗前,采用飞利浦iU22彩色多普勒超声诊断仪对病灶进行检查,观察并记录定性和定量参数。新辅助化疗结束后行肿块切除术,由2位病理学副主任及以上医师依据Miller and Payne改良病理反应分级标准评估疗效,分为病理完全应答(pathological complete response,PCR)组(102例)和非PCR组(90例);采用免疫组织化学法检测组织中的CBLC、COL10A1表达水平。结果单因素分析结果表明,非PCR组的增强边界不清晰、出现灌注缺损、周围放射状增强和增强不均匀的比例显著高于PCR组,非PCR组的峰值强度(peak intensity,PI)和曲线下面积(area under curve,AUC)均显著高于PCR组(均P<0.05);CBLC高表达者出现高增强、增强边界不清晰、灌注缺损、增强不均匀的比例显著低于低表达者,PI和AUC均显著低于低表达者(均P<0.05);COL10A1高表达者出现高增强、周围放射状增强、增强不均匀的比例显著高于低表达者,PI和AUC均显著高于低表达者,而达峰时间(time to peak,TTP)显著低于低表达者(均P<0.05)。多因素Logistic回归分析结果显示,增强边界不清晰、PI及AUC增大是出现非PCR的独立危险因素(均P<0.05);高增强、增强边界不清晰、PI及AUC增大是CBLC低表达的独立危险因素(均P<0.05);高增强、PI增大及TTP减小是COL10A1高表达的独立危险因素(均P<0.05)。结论超声造影定性及定量参数可用于预测乳腺癌患者新辅助化疗疗效及CBLC、COL10A1表达水平,有助于选择治疗方案和预测患者预后。
基金funded by the Scientific research Project Plan of Shanghai Municipal Health Commission(No.202140346)the National Key Research and Development Program of China(No.2016YFC0901505).
文摘Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese cases with CblC disease.Methods We carried out a national,retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G>A variant either in a homozygous or compound heterozygous state.The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G>A mutation.Clinical features,including disease onset,symptoms,biochemical metabolites,gene mutation,and follow-up outcomes were reviewed and analyzed in detail.The median follow-up period spanned 3 years and 8 months,with a range of 1 year and 2 months to 12 years and 10 months.Results Among 195 patients carrying the c.482G>A variant,125(64.1%)cases were diagnosed by newborn screening(NBS),60(30.8%)cases were detected due to disease onset,and 10(5.1%)cases were identified from sibling diagnoses.One hundred and seventeen(93.6%)individuals who were diagnosed by NBS,and nine patients who came from sibling diagnoses remained asymptomatic in this study.From 69 symptomatic patients of the c.482G>A group,more patients presented with later onset,and the top six common clinical symptoms at disease onset were developmental delay(59.4%),lower limb weakness and poor exercise tolerance(50.7%),cognitive decline(37.7%),gait instability and abnormal posture(36.2%),seizures(26.1%),and psychiatric and behavioral disturbances(24.6%).In the 159 symptomatic patients lacking c.482G>A variants,the most frequently observed clinical manifestations at disease onset included developmental delay(81.8%),lethargy and feeding difficulty(62.9%),lower limb weakness and poor exercise tolerance(54.7%),prolonged neonatal jaundice(51.6%),vomiting(47.2%),and seizures(32.7%).Before treatment,the levels of blood propionylcarnitine,propionylcarnitine/acetylcarnitine ratio,and homocysteine in the c.482G>A group were significantly lower(P<0.05)than those in the non-c.482G>A group,while the concentration of urinary methylmalonic acid was slightly lower(P>0.05).The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels(P<0.05).In patients carrying the c.482G>A variant compared with the non-c.428G>A group,there were markedly lower rates of mortality(0.5%vs.2.0%)and developmental delay(20.5%vs.65.5%).When compared with individuals diagnosed due to disease onset,those identified through NBS in either group exhibited a reduced proportion of disease onset(6.7%vs.100%in the c.482G>A group,54.4%vs.100%in the non-c.482G>A group),lower mortality(0.0%vs.1.7%in the c.482G>A group,0.0%vs.3.6%in the non-c.482G>A group),and had a higher percentage of patients exhibiting normal psychomotor and language development(99.3%vs.33.3%in the c.482G>A group,58.9%vs.10.9%in the non-c.482G>A group).Conclusions The c.482G>A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease.Patients with this mutation tend to have a relatively better response to hydroxocobalamin,better metabolic control,and more favorable neurological outcomes.NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis,resulting in favorable clinical outcomes.
