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[Chemotherapy-free induction therapy for a critically ill pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case report and literature review]. [费城染色体阳性急性淋巴细胞白血病危重孕妇的无化疗诱导治疗:1例报告及文献复习]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250519-00235
M Gao, Y Xie, Z Y Liu, P Q Liang, L M Liu, J Yin, D Wang, B Han, H Y Qiu, J H Fu, D P Wu

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph(+) ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

本文报告了一位36岁的危重女性,在妊娠28周时被诊断为费城染色体阳性急性淋巴细胞白血病(Ph(+)ALL)。患者病情迅速恶化,出现弥漫性血管内凝血(DIC)、弥漫性肺泡出血(DAH)、感染性休克和多器官功能障碍,需要住进血液重症监护室。鉴于患者病情危重且妊娠晚期,我们开始了不含化疗的诱导治疗方案,包括伊马替尼和地塞米松,同时采取综合支持措施,包括机械通气、持续肾替代治疗(CRRT)、广谱抗生素和大剂量皮质类固醇。在治疗期间,发生了宫内胎儿死亡,并在产科干预后分娩了死胎。通过积极治疗,患者的呼吸衰竭、DIC和DAH逐渐消失,患者完全缓解。随后,她接受了巩固化疗、CAR-T细胞治疗和异体造血干细胞移植,在长期随访中实现了持续的完全分子缓解。该病例表明,对于患有Ph(+) ALL的危重妊娠患者,靶向治疗和皮质类固醇的无化疗方案,结合强化支持治疗,是一种安全有效的方法,可能为类似病例提供治疗选择。
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引用次数: 0
[Systemic necrotizing lymphadenitis: a case report]. 系统性坏死性淋巴结炎1例。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250702-00309
L L Fu, S Sun, D D Wang, J N Li
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引用次数: 0
[Prognostic value of high-risk cytogenetic abnormalities inmultiple myeloma]. [多发性骨髓瘤高危细胞遗传学异常的预后价值]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250120-00035
X X Shen, J P Yu, R Guo, Y Xu, Y Y Jin, Q L Shi, L J Chen

To retrospectively analyze the clinical data of 465 newly diagnosed patients with multiple myeloma (NDMM) admitted to the First Affiliated Hospital of Nanjing Medical University from December 2016 to December 2024, and compare the prognostic value of high-risk cytogenetic abnormalities (HRCAs) in NDMM patients under mSMART 3.0 and mSMART 4.0 risk stratification systems. The results showed that in both stratification systems, the prognosis of high-risk patients was worse than that of standard-risk patients. Moreover, a higher number of HRCAs was associated with a worse prognosis. The mSMART 4.0 system, which considers the coexistence of various cytogenetic abnormalities, provides a more precise definition of HRCA than mSMART 3.0. It demonstrates a superior ability to differentiate between different categories of cytogenetic risk.

回顾性分析2016年12月至2024年12月南京医科大学第一附属医院465例新诊断的多发性骨髓瘤(NDMM)患者的临床资料,比较mSMART 3.0和mSMART 4.0风险分层系统下高危细胞遗传学异常(HRCAs)在NDMM患者中的预后价值。结果显示,在两种分层系统中,高危患者的预后均较标准危患者差。此外,hrca数量越多,预后越差。mSMART 4.0系统考虑了各种细胞遗传学异常的共存,提供了比mSMART 3.0更精确的HRCA定义。它显示了区分不同类型的细胞遗传风险的优越能力。
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引用次数: 0
[Analysis of peripheral blood monocyte subsets in chronic myelomonocytic leukemia: a single-center study]. [慢性髓单细胞白血病外周血单核细胞亚群分析:单中心研究]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250126-00045
L Wang, M M Li, J J Bai, C X Deng, P Wu, C W Luo, P L Lai, J Y Weng, X Du

Objective: To evaluate the clinical value of peripheral blood monocyte subset analysis in the diagnosis and treatment of chronic myelomonocytic leukemia (CMML) . Method: We retrospectively enrolled 51 patients newly diagnosed with CMML at Guangdong Provincial People's Hospital between June 1, 2020, and December 31, 2024, according to the WHO 2022 diagnostic criteria. Twenty-three patients with other myeloid neoplasms (excluding CMML) and peripheral monocytosis (absolute count ≥0.5×10(9)/L and percentage ≥10%) were included as the control group. All patients underwent bone marrow aspiration for examinations including bone marrow smears, biopsies, cytogenetics, and gene mutation analysis to establish a definitive diagnosis. Concurrently, flow cytometry was used to determine the proportions of peripheral blood monocyte subsets: classical (MO1, CD14(+)CD16(-)) , intermediate (MO2, CD14(+)CD16(+)) , and non-classical (MO3, CD14(low)CD16(+)) . Differences between the groups were compared, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. Result: Among the 51 CMML patients, the proportion of the peripheral blood MO1 subset was significantly higher than that in patients with other myeloid neoplasms (P=0.027) , whereas there were no significant differences in the MO2 and MO3 subsets (all P>0.05) . Further analysis revealed that 43 (84.31%) of the CMML patients met the WHO diagnostic threshold for the MO1 subset (≥94%) , while the remaining 8 patients did not; 46 patients (90.20%) had MO3 subset proportions below the threshold proposed by Hudson (≤1.13%) , while the remaining 5 patients were above this threshold. In-depth analysis showed that among the 8 patients who did not meet the WHO criteria, 7 were experiencing inflammation. Similarly, all 5 patients who did not meet the Hudson criteria were in an inflammatory state. Subsequent ROC curve analysis of this cohort identified a cut-off value for the MO1 subset of 97.55% [Area Under the Curve (AUC) =0.661, P=0.027], which aligns with the WHO criteria. Conclusion: Peripheral blood monocyte subset analysis, particularly MO1 subset analysis, can effectively assist in CMML diagnosis, but exclusion of inflammatory conditions is required.

目的:探讨外周血单核细胞亚群分析在慢性髓单细胞白血病(CMML)诊治中的临床价值。方法:根据WHO 2022诊断标准,回顾性纳入广东省人民医院2020年6月1日至2024年12月31日期间新诊断为CMML的51例患者。其他髓系肿瘤(CMML除外)伴外周单核细胞增多症(绝对计数≥0.5×10(9)/L,百分比≥10%)患者23例作为对照组。所有患者均行骨髓穿刺检查,包括骨髓涂片、活检、细胞遗传学和基因突变分析,以确定明确的诊断。同时,流式细胞术测定外周血单核细胞亚群的比例:经典(MO1, CD14(+)CD16(-)),中间(MO2, CD14(+)CD16(+))和非经典(MO3, CD14(低)CD16(+))。比较两组间的差异,并采用受试者工作特征(ROC)曲线评价诊断效果。结果:51例CMML患者外周血MO1亚群比例显著高于其他髓系肿瘤患者(P=0.027),而MO2、MO3亚群比例差异无统计学意义(P均为0.05)。进一步分析显示,43例(84.31%)CMML患者符合WHO对MO1亚群的诊断阈值(≥94%),其余8例患者不符合;46例(90.20%)患者的MO3亚群比例低于Hudson提出的阈值(≤1.13%),其余5例患者高于该阈值。深入分析显示,在不符合世卫组织标准的8例患者中,有7例出现炎症。同样,不符合Hudson标准的5例患者均处于炎症状态。随后对该队列进行ROC曲线分析,确定MO1亚群的临界值为97.55%[曲线下面积(AUC) =0.661, P=0.027],符合WHO标准。结论:外周血单核细胞亚群分析特别是MO1亚群分析可有效辅助CMML的诊断,但需排除炎症情况。
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引用次数: 0
[Clinical and molecular characteristics of myeloproliferative neoplasms patients with NFE2 gene mutations]. 【NFE2基因突变骨髓增生性肿瘤患者的临床及分子特征】。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20241214-00569
S Y Zhao, B Li, Z F Xu, T J Qin, S Q Qu, L J Pan, M Jiao, Q Y Gao, H J Wang, Q Sun, Y J Jia, Y R Yan, J Y Gong, F H Li, X Wang, Z J Xiao
<p><p><b>Objective:</b> To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations. <b>Methods:</b> Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed. <b>Results:</b> Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) (<i>P</i><0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years <i>vs</i> 54 (41, 63) years, <i>P</i>=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% <i>vs</i> 22.0%, <i>P</i>=0.012) and pre-diagnosis arterial thrombosis (36.6% <i>vs</i> 20.4%, <i>P</i>=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) (<i>OR</i>=2.747, 95%<i>CI</i>: 1.143-6.605, <i>P</i>=0.024) , interferon-gamma (IFN-γ) (<i>OR</i>=2.689, 95%<i>CI</i>: 1.191-6.076, <i>P</i>=0.017) , IL-10 (<i>OR</i>=3.219, 95% <i>CI</i>: 1.343-7.717, <i>P</i>=0.009) , IL-12P70 (<i>OR</i>=3.397, 95%<i>CI</i>:1.003-11.508, <i>P</i>=0.049) , IL-17 (<i>OR</i>=2.284, 95%<i>CI</i>: 1.017-5.127, <i>P</i>=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% <i>vs</i> 25.3% for IWG-PV, <i>P</i>=0.033; 22.2% <i>vs</i> 2.0% for MIPSS-PV, <i>P</i>=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% <i>vs</i> 6.1%, <i>P</i>=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, <i>P</i>>0.05) . <b>Conclusion:</b> NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene
目的:探讨骨髓增生性肿瘤(mpn) NFE2基因突变患者的临床特点及分子特征。方法:采用基因靶向测序检测2021年4月至2023年6月在中国医学科学院血液学血液病研究所和北京协和医学院住院的723例MPNs患者的NFE2基因突变。回顾性分析NFE2基因突变与MPNs患者临床特征及分子特征的关系。结果:723例MPNs患者中,NFE2基因突变41例(5.7%)。NFE2基因突变以移码突变为主(44.4%),其次是无义突变(33.3%)。NFE2基因突变患者的中位突变数(4[2,5])高于无NFE2基因突变组(2,[1,3])(Pvs 54(41,63)年,P=0.001)。NFE2基因突变患者的诊断前血栓发生率(39.0% vs 22.0%, P=0.012)和诊断前动脉血栓发生率(36.6% vs 20.4%, P=0.014)较高。通过调整年龄和合共病(包括慢性感染、恶性肿瘤和自身免疫性疾病)的logistic回归分析模型,确定NFE2基因突变是肿瘤坏死因子-α (TNF-α) (OR=2.747, 95%CI: 1.143-6.605, P=0.024)、干扰素-γ (IFN-γ) (OR=2.689, 95%CI: 1.191-6.076, P=0.017)、IL-10 (OR=3.219, 95%CI: 1.343-7.717, P=0.009)、IL-12P70 (OR=3.397, 95%CI:1.003-11.508, P=0.049)、IL-17 (OR=2.284, 95%CI: P=0.049)升高的独立决定因素。1.017-5.127, p =0.045)。在NFE2基因突变的真性红细胞增多症(PV)患者中,在IWG-PV和突变增强的PV国际预后系统(MIPSS-PV)中,被归类为高风险的比例明显更高(IWG-PV为66.7% vs 25.3%, P=0.033; MIPSS-PV为22.2% vs 2.0%, P=0.013)。同样,对于原发性血小板增多症(ET)患者,突变增强的ET国际预后系统(MIPSS-ET)在高危人群中的比例明显更高(15.4% vs 6.1%, P=0.021)。nfe2突变(38例)与非突变(671例,P < 0.05) mpn患者的总生存期和累计血栓发生率无统计学差异。结论:NFE2基因在mpn中以移码突变为主。NFE2基因突变与年龄增大、多种炎症因子(TNF-α、IFN-γ、IL-10、IL-12P70、IL-17)水平升高相关,且多发生在mpn晚期。
{"title":"[Clinical and molecular characteristics of myeloproliferative neoplasms patients with NFE2 gene mutations].","authors":"S Y Zhao, B Li, Z F Xu, T J Qin, S Q Qu, L J Pan, M Jiao, Q Y Gao, H J Wang, Q Sun, Y J Jia, Y R Yan, J Y Gong, F H Li, X Wang, Z J Xiao","doi":"10.3760/cma.j.cn121090-20241214-00569","DOIUrl":"10.3760/cma.j.cn121090-20241214-00569","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations. &lt;b&gt;Methods:&lt;/b&gt; Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed. &lt;b&gt;Results:&lt;/b&gt; Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) (&lt;i&gt;P&lt;/i&gt;&lt;0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years &lt;i&gt;vs&lt;/i&gt; 54 (41, 63) years, &lt;i&gt;P&lt;/i&gt;=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% &lt;i&gt;vs&lt;/i&gt; 22.0%, &lt;i&gt;P&lt;/i&gt;=0.012) and pre-diagnosis arterial thrombosis (36.6% &lt;i&gt;vs&lt;/i&gt; 20.4%, &lt;i&gt;P&lt;/i&gt;=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) (&lt;i&gt;OR&lt;/i&gt;=2.747, 95%&lt;i&gt;CI&lt;/i&gt;: 1.143-6.605, &lt;i&gt;P&lt;/i&gt;=0.024) , interferon-gamma (IFN-γ) (&lt;i&gt;OR&lt;/i&gt;=2.689, 95%&lt;i&gt;CI&lt;/i&gt;: 1.191-6.076, &lt;i&gt;P&lt;/i&gt;=0.017) , IL-10 (&lt;i&gt;OR&lt;/i&gt;=3.219, 95% &lt;i&gt;CI&lt;/i&gt;: 1.343-7.717, &lt;i&gt;P&lt;/i&gt;=0.009) , IL-12P70 (&lt;i&gt;OR&lt;/i&gt;=3.397, 95%&lt;i&gt;CI&lt;/i&gt;:1.003-11.508, &lt;i&gt;P&lt;/i&gt;=0.049) , IL-17 (&lt;i&gt;OR&lt;/i&gt;=2.284, 95%&lt;i&gt;CI&lt;/i&gt;: 1.017-5.127, &lt;i&gt;P&lt;/i&gt;=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% &lt;i&gt;vs&lt;/i&gt; 25.3% for IWG-PV, &lt;i&gt;P&lt;/i&gt;=0.033; 22.2% &lt;i&gt;vs&lt;/i&gt; 2.0% for MIPSS-PV, &lt;i&gt;P&lt;/i&gt;=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% &lt;i&gt;vs&lt;/i&gt; 6.1%, &lt;i&gt;P&lt;/i&gt;=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, &lt;i&gt;P&lt;/i&gt;&gt;0.05) . &lt;b&gt;Conclusion:&lt;/b&gt; NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene ","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"46 10","pages":"943-951"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Progress in metabolomics of multiple myeloma]. [多发性骨髓瘤代谢组学研究进展]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20241205-00536
X Ye, Z X Sun, X Y Qu, L Fan

Multiple myeloma (MM) is a malignant disease characterized by clonal plasma cell proliferation, with metabolic reprogramming. Abnormal metabolism of amino acids, glucose, lipids and nucleotides plays a crucial role in various pathological processes in MM, such as proliferation, metastasis, immune escaping and drug resistance. This review summarized the application of metabolomics technology in identifying biomarkers for MM and targeting related metabolic pathways. The objective is to guide further investigations into the metabolic mechanisms underlying MM and encourage innovation in clinical diagnosis and treatment strategies for this disease.

多发性骨髓瘤(MM)是一种以克隆性浆细胞增殖为特征的恶性疾病,伴有代谢重编程。氨基酸、葡萄糖、脂质和核苷酸的异常代谢在MM的增殖、转移、免疫逃逸和耐药等多种病理过程中起着至关重要的作用。本文综述了代谢组学技术在识别MM生物标志物和靶向相关代谢途径中的应用。目的是指导进一步研究MM的代谢机制,并鼓励临床诊断和治疗策略的创新。
{"title":"[Progress in metabolomics of multiple myeloma].","authors":"X Ye, Z X Sun, X Y Qu, L Fan","doi":"10.3760/cma.j.cn121090-20241205-00536","DOIUrl":"10.3760/cma.j.cn121090-20241205-00536","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a malignant disease characterized by clonal plasma cell proliferation, with metabolic reprogramming. Abnormal metabolism of amino acids, glucose, lipids and nucleotides plays a crucial role in various pathological processes in MM, such as proliferation, metastasis, immune escaping and drug resistance. This review summarized the application of metabolomics technology in identifying biomarkers for MM and targeting related metabolic pathways. The objective is to guide further investigations into the metabolic mechanisms underlying MM and encourage innovation in clinical diagnosis and treatment strategies for this disease.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"46 10","pages":"980-984"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Methodological appraisal of statistical approaches to evaluating the impact of chronic graft-versus-host disease on mortality after hematopoietic stem cell transplantation]. [评估慢性移植物抗宿主病对造血干细胞移植后死亡率影响的统计方法的方法学评价]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250731-00356
J J Wu, J F Wang

Objective: Using the impact of chronic graft-versus-host disease (cGVHD) on overall survival after hematopoietic stem cell transplantation as an example, this study aims to introduces and critically appraises five statistical approaches for handling time-dependent events in survival analysis. Methods: This study was based on data from the Center for International Blood and Marrow Transplant Research (CIBMTR) GV18-03 study. A total of 4361 patients with acute myeloid leukemia or myelodysplastic syndrome were included, who were aged ≥40 years and had received an HLA 8/8 matched sibling donor transplant between 2008 and 2017. Five analytical approaches were used, treating cGVHD as: ① a baseline fixed covariate, ② a time-dependent covariate, ③ a time-dependent event via landmarking analysis, ④ a transitional event in a multi-state model, and ⑤ an exposure in the parametric g-formula. For each approach, we presented its core concept and results, and elaborated on its rationale, strengths, limitations, and applicable scenarios. Results: The five approaches showed significant differences in bias control, modeling flexibility, and clinical interpretability. Method 1 was prone to immortal time bias. Method 2 partially corrected this bias but was vulnerable to informative censoring and estimation instability due to insufficient sample sizes in the early-onset cGVHD group. Method 3 was straightforward but dependent on a predefined landmark time point and unable to account for cGVHD occurring after this point. Method 4 allowed for a comprehensive description of the impact of time-dependent events on survival prognosis by modeling dynamic clinical transitions. Method 5 could simultaneously handle both time-dependent events and confounders, making it suitable for estimating population-level effects of specific exposure strategies. Conclusion: Researchers should select the appropriate method based on their specific study objectives to ensure that the estimation of the impact of time-dependent events on outcomes is both statistically valid and clinically meaningful.

目的:以慢性移植物抗宿主病(chronic graft- anti -host disease, cGVHD)对造血干细胞移植后总生存率的影响为例,介绍并批判性评价在生存分析中处理时间依赖性事件的五种统计方法。方法:本研究基于国际血液和骨髓移植研究中心(CIBMTR) GV18-03研究的数据。共纳入4361例急性髓性白血病或骨髓增生异常综合征患者,年龄≥40岁,在2008年至2017年期间接受了HLA 8/8匹配的兄弟姐妹供体移植。采用五种分析方法,将cGVHD视为:①基线固定协变量,②时间相关协变量,③通过地标分析的时间相关事件,④多状态模型中的过渡事件,以及⑤参数g公式中的暴露。对于每种方法,我们都介绍了其核心概念和结果,并详细阐述了其基本原理、优势、局限性和适用场景。结果:五种方法在偏倚控制、建模灵活性和临床可解释性方面存在显著差异。方法一易出现不朽时间偏差。方法2部分纠正了这一偏差,但由于早发性cGVHD组的样本量不足,容易受到信息审查和估计不稳定的影响。方法3是直接的,但依赖于一个预定义的里程碑时间点,无法解释cGVHD发生在这一点之后。方法4允许通过模拟动态临床转变来全面描述时间依赖性事件对生存预后的影响。方法5可以同时处理时间相关事件和混杂因素,使其适合于估计特定暴露策略的人群水平效应。结论:研究者应根据其具体的研究目的选择合适的方法,以确保对时间相关事件对结果影响的估计在统计上有效且具有临床意义。
{"title":"[Methodological appraisal of statistical approaches to evaluating the impact of chronic graft-versus-host disease on mortality after hematopoietic stem cell transplantation].","authors":"J J Wu, J F Wang","doi":"10.3760/cma.j.cn121090-20250731-00356","DOIUrl":"10.3760/cma.j.cn121090-20250731-00356","url":null,"abstract":"<p><p><b>Objective:</b> Using the impact of chronic graft-versus-host disease (cGVHD) on overall survival after hematopoietic stem cell transplantation as an example, this study aims to introduces and critically appraises five statistical approaches for handling time-dependent events in survival analysis. <b>Methods:</b> This study was based on data from the Center for International Blood and Marrow Transplant Research (CIBMTR) GV18-03 study. A total of 4361 patients with acute myeloid leukemia or myelodysplastic syndrome were included, who were aged ≥40 years and had received an HLA 8/8 matched sibling donor transplant between 2008 and 2017. Five analytical approaches were used, treating cGVHD as: ① a baseline fixed covariate, ② a time-dependent covariate, ③ a time-dependent event via landmarking analysis, ④ a transitional event in a multi-state model, and ⑤ an exposure in the parametric g-formula. For each approach, we presented its core concept and results, and elaborated on its rationale, strengths, limitations, and applicable scenarios. <b>Results:</b> The five approaches showed significant differences in bias control, modeling flexibility, and clinical interpretability. Method 1 was prone to immortal time bias. Method 2 partially corrected this bias but was vulnerable to informative censoring and estimation instability due to insufficient sample sizes in the early-onset cGVHD group. Method 3 was straightforward but dependent on a predefined landmark time point and unable to account for cGVHD occurring after this point. Method 4 allowed for a comprehensive description of the impact of time-dependent events on survival prognosis by modeling dynamic clinical transitions. Method 5 could simultaneously handle both time-dependent events and confounders, making it suitable for estimating population-level effects of specific exposure strategies. <b>Conclusion:</b> Researchers should select the appropriate method based on their specific study objectives to ensure that the estimation of the impact of time-dependent events on outcomes is both statistically valid and clinically meaningful.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"46 10","pages":"905-913"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[A preliminary analysis of the efficacy and safety of homoharringtonine, venetoclax, and azacitidine for newly diagnosed acute myeloid leukemia]. 【高杉碱、venetoclax和阿扎胞苷治疗新诊断急性髓系白血病的疗效和安全性初步分析】。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20241111-00443
H Ai, Q Wang, H F Wu, Q S Yin
<p><p><b>Objective:</b> To compare the efficacy and safety of two induction regimens, homoharringtonine plus venetoclax and azacitidine (VHA) versus venetoclax and azacitidine (VA) , for newly diagnosed acute myeloid leukemia (AML) patients who are elderly or ineligible for intensive chemotherapy. <b>Methods:</b> We retrospectively analyzed the clinical data of 59 newly diagnosed AML patients treated with the VHA or VA regimen at Zhengzhou University Affiliated Cancer Hospital from September 2018 to July 2021. The cohort included 25 males and 34 females, with a median age of 63 years. The overall response rate (ORR) , composite complete remission (CRc) rate [CR+CR with incomplete hematologic recovery (CRi) ], minimal residual disease (MRD) negativity rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were compared between the two groups. Survival was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using univariable and multivariable Cox regression. <b>Results:</b> At the end of the treatment, the ORR was 88.4% (23/26) in the VHA group [21 CR, 2 partial remissions (PR) ] and 90.9% (30/33) in the VA group (25 CR, 5 PR) , with no significant difference between the groups (<i>P</i>=0.458) . The MRD negativity rates after one cycle of induction were 73.1% (19/26) in the VHA group and 60.6% (20/33) in the VA group, respectively (<i>P</i>=0.315) . In the high-risk subgroup, the composite remission rates after one cycle were 78.6% (11/14) with VHA and 50.0% (5/10) with VA (<i>P</i>=0.143) ; MRD negativity rates were 64.3% (9/14) and 20.0% (2/10) , respectively (<i>P</i>=0.032) . The main adverse events were myelosuppression, gastrointestinal reactions, and infections during neutropenia. Rates of grade 3-4 neutropenia and decreased hemoglobin were similar between groups, whereas grade 3-4 thrombocytopenia was more frequent with VHA than with VA (76.9% <i>vs</i> 45.5%, <i>P</i>=0.015) . With a median follow-up of 13 months (range, 1-59) , 1 year RFS was 69.9% (95% <i>CI</i>: 53.1%-92.2%) with VHA and 55.6% (95% <i>CI</i>: 40.1%-77.1%) with VA (<i>P</i>=0.305) . The 1 year OS rates were 91.7% (95% <i>CI</i>: 77.3%-100.0%) and 58.2% (95% <i>CI</i>: 41.7%-81.4%) , respectively (<i>P</i>=0.024) . Among high risk patients, 1 year RFS and OS were higher with VHA than with VA (RFS: 66.2% <i>vs</i> 37.5%, <i>P</i>=0.046; OS: 85.7% <i>vs</i> 48.0%, <i>P</i>=0.011) . Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS (<i>P</i>=0.027 and 0.047, respectively) . On multivariable analysis, ELN risk classification and MRD negativity after the first cycle were independent prognostic factors for RFS. Treatment regimen (VHA <i>vs</i> VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. <b>Conclusion:</b> VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemo
目的:比较高杉酸酯碱联合venetoclax和阿扎胞苷(VHA)与venetoclax和阿扎胞苷(VA)两种诱导方案对老年或不适合强化化疗的新诊断急性髓系白血病(AML)患者的疗效和安全性。方法:回顾性分析2018年9月至2021年7月郑州大学附属肿瘤医院59例新诊断AML患者VHA或VA方案的临床资料。该队列包括25名男性和34名女性,中位年龄为63岁。比较两组患者的总缓解率(ORR)、复合完全缓解率(CRc) [CR+CR伴不完全血液学恢复(CRi)]、最小残留病(MRD)阴性率、总生存期(OS)、无复发生存期(RFS)、不良事件。生存率采用Kaplan-Meier法估计,预后因素采用单变量和多变量Cox回归评估。结果:治疗结束时,VHA组[21 CR, 2 PR]的ORR为88.4% (23/26),VA组(25 CR, 5 PR)的ORR为90.9%(30/33),两组间差异无统计学意义(P=0.458)。1周期诱导后,VHA组MRD阴性率为73.1% (19/26),VA组为60.6%(20/33),差异有统计学意义(P=0.315)。高危亚组一个周期后综合缓解率VHA组为78.6% (11/14),VA组为50.0% (5/10)(P=0.143);MRD阴性率分别为64.3%(9/14)和20.0% (2/10)(P=0.032)。中性粒细胞减少期间的主要不良事件为骨髓抑制、胃肠道反应和感染。3-4级中性粒细胞减少和血红蛋白降低的发生率在两组之间相似,而VHA组的3-4级血小板减少发生率高于VA组(76.9% vs 45.5%, P=0.015)。中位随访13个月(范围1-59),VHA组1年RFS为69.9% (95% CI: 53.1%-92.2%), VA组为55.6% (95% CI: 40.1%-77.1%) (P=0.305)。1年OS率分别为91.7% (95% CI: 77.3% ~ 100.0%)和58.2% (95% CI: 41.7% ~ 81.4%) (P=0.024)。在高危患者中,VHA组1年RFS和OS高于VA组(RFS: 66.2% vs 37.5%, P=0.046; OS: 85.7% vs 48.0%, P=0.011)。同种异体造血干细胞移植(allogeneic hematopoietic stem cell transplantation, alloo - hsct)可显著改善RFS和OS (P=0.027和0.047)。在多变量分析中,ELN风险分类和第一周期后MRD阴性是RFS的独立预后因素。治疗方案(VHA vs VA)、第一周期后MRD阴性和接受移植是OS的独立预后因素。结论:VHA在新诊断的不适合强化化疗的AML患者和老年人中提供临床益处,对高危患者尤其有利;序贯的同种异体造血干细胞移植带来了额外的益处,并且相关的不良事件是可控的。
{"title":"[A preliminary analysis of the efficacy and safety of homoharringtonine, venetoclax, and azacitidine for newly diagnosed acute myeloid leukemia].","authors":"H Ai, Q Wang, H F Wu, Q S Yin","doi":"10.3760/cma.j.cn121090-20241111-00443","DOIUrl":"10.3760/cma.j.cn121090-20241111-00443","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; To compare the efficacy and safety of two induction regimens, homoharringtonine plus venetoclax and azacitidine (VHA) versus venetoclax and azacitidine (VA) , for newly diagnosed acute myeloid leukemia (AML) patients who are elderly or ineligible for intensive chemotherapy. &lt;b&gt;Methods:&lt;/b&gt; We retrospectively analyzed the clinical data of 59 newly diagnosed AML patients treated with the VHA or VA regimen at Zhengzhou University Affiliated Cancer Hospital from September 2018 to July 2021. The cohort included 25 males and 34 females, with a median age of 63 years. The overall response rate (ORR) , composite complete remission (CRc) rate [CR+CR with incomplete hematologic recovery (CRi) ], minimal residual disease (MRD) negativity rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were compared between the two groups. Survival was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using univariable and multivariable Cox regression. &lt;b&gt;Results:&lt;/b&gt; At the end of the treatment, the ORR was 88.4% (23/26) in the VHA group [21 CR, 2 partial remissions (PR) ] and 90.9% (30/33) in the VA group (25 CR, 5 PR) , with no significant difference between the groups (&lt;i&gt;P&lt;/i&gt;=0.458) . The MRD negativity rates after one cycle of induction were 73.1% (19/26) in the VHA group and 60.6% (20/33) in the VA group, respectively (&lt;i&gt;P&lt;/i&gt;=0.315) . In the high-risk subgroup, the composite remission rates after one cycle were 78.6% (11/14) with VHA and 50.0% (5/10) with VA (&lt;i&gt;P&lt;/i&gt;=0.143) ; MRD negativity rates were 64.3% (9/14) and 20.0% (2/10) , respectively (&lt;i&gt;P&lt;/i&gt;=0.032) . The main adverse events were myelosuppression, gastrointestinal reactions, and infections during neutropenia. Rates of grade 3-4 neutropenia and decreased hemoglobin were similar between groups, whereas grade 3-4 thrombocytopenia was more frequent with VHA than with VA (76.9% &lt;i&gt;vs&lt;/i&gt; 45.5%, &lt;i&gt;P&lt;/i&gt;=0.015) . With a median follow-up of 13 months (range, 1-59) , 1 year RFS was 69.9% (95% &lt;i&gt;CI&lt;/i&gt;: 53.1%-92.2%) with VHA and 55.6% (95% &lt;i&gt;CI&lt;/i&gt;: 40.1%-77.1%) with VA (&lt;i&gt;P&lt;/i&gt;=0.305) . The 1 year OS rates were 91.7% (95% &lt;i&gt;CI&lt;/i&gt;: 77.3%-100.0%) and 58.2% (95% &lt;i&gt;CI&lt;/i&gt;: 41.7%-81.4%) , respectively (&lt;i&gt;P&lt;/i&gt;=0.024) . Among high risk patients, 1 year RFS and OS were higher with VHA than with VA (RFS: 66.2% &lt;i&gt;vs&lt;/i&gt; 37.5%, &lt;i&gt;P&lt;/i&gt;=0.046; OS: 85.7% &lt;i&gt;vs&lt;/i&gt; 48.0%, &lt;i&gt;P&lt;/i&gt;=0.011) . Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS (&lt;i&gt;P&lt;/i&gt;=0.027 and 0.047, respectively) . On multivariable analysis, ELN risk classification and MRD negativity after the first cycle were independent prognostic factors for RFS. Treatment regimen (VHA &lt;i&gt;vs&lt;/i&gt; VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. &lt;b&gt;Conclusion:&lt;/b&gt; VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemo","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"46 10","pages":"937-942"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[The guideline for the diagnosis and treatment of marginal zone lymphoma in China (2025)]. [中国边缘带淋巴瘤诊疗指南(2025)]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250612-00273

Marginal zone lymphoma (MZL) is an indolent B-cell lymphoma arising from marginal zone B cells within lymphoid follicles, accounting for approximately 5%-15% of non-Hodgkin lymphomas. MZL is characterized by diagnostic challenges and diverse treatment options, making it a challenging subtype in clinical practice. In recent years, with the rapid progress in lymphoma research, the understanding of MZL has improved significantly worldwide. To further standardize the diagnosis and treatment of MZL in China, the Chinese Workshop of Indolent Lymphomas convened a panel of national experts. Based on thorough discussion and consensus, this guideline was developed to provide a reference for medical practitioners.

边缘带淋巴瘤(MZL)是一种起源于淋巴滤泡边缘带B细胞的惰性B细胞淋巴瘤,约占非霍奇金淋巴瘤的5%-15%。MZL的特点是诊断困难和多种治疗选择,使其成为临床实践中具有挑战性的亚型。近年来,随着淋巴瘤研究的快速进展,世界范围内对MZL的认识有了显著提高。为了进一步规范中国惰性淋巴瘤的诊断和治疗,中国惰性淋巴瘤研讨会召集了全国专家小组。本指南是在深入讨论和共识的基础上制定的,旨在为医疗从业者提供参考。
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引用次数: 0
[Efficacy and safety of lusutrombopag monotherapy for cyclosporine A-refractory, transfusion-dependent non-severe aplastic anemia]. [lusutrombopag单药治疗环孢素a难治性输血依赖性非严重再生障碍性贫血的疗效和安全性]。
Q3 Medicine Pub Date : 2025-10-14 DOI: 10.3760/cma.j.cn121090-20250225-00094
Y X Zhou, Y Y Wei, Z W Liu, C Yang, M Chen, B Han

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

本研究回顾性分析了12例输血依赖性非严重再生障碍性贫血(TD-NSAA)患者对环孢素A (CsA)难治性,并采用lusutrombopag单药治疗。这些患者要么有各种慢性合并症或药物相关风险,要么对其他血小板生成素受体激动剂(TPO-RA)无反应或不耐受。lusutrombopag的中位治疗时间为4个月(范围:3-11个月),中位随访时间为8个月(范围:6-11个月)。随访3个月、6个月和结束时的总缓解率(OR)分别为50.0%、58.3%和50.0%,达到OR的中位时间为2个月(范围:1-4个月)。在同一时间点,完全缓解(CR)率分别为8.3%、16.7%和16.7%,达到CR的中位时间为4个月(范围:2-5个月)。不良事件均为1级,发生率为25.0%。随访期间,1例患者停药后OR丧失,复发率为14.3%;未观察到克隆进化或死亡。这些研究结果表明,lusutrombopag在csa难治性TD-NSAA患者中既有效又耐受性良好,对于治疗耐受性差的患者来说是一种有希望的治疗选择。
{"title":"[Efficacy and safety of lusutrombopag monotherapy for cyclosporine A-refractory, transfusion-dependent non-severe aplastic anemia].","authors":"Y X Zhou, Y Y Wei, Z W Liu, C Yang, M Chen, B Han","doi":"10.3760/cma.j.cn121090-20250225-00094","DOIUrl":"10.3760/cma.j.cn121090-20250225-00094","url":null,"abstract":"<p><p>This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":"46 10","pages":"963-966"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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