达雷妥尤单抗治疗复发/难治性多发性骨髓瘤疗效观察研究

背景　多发性骨髓瘤不可治愈,绝大多数患者终将复发。达雷妥尤单抗是一种人源化、抗CD38单克隆抗体,国外研究达雷妥尤单抗复发/难治性多发性骨髓瘤疗效显著,我国患者临床使用数据有限。目的　观察达雷妥尤单抗治疗复发/难治性多发性骨髓瘤临床疗效及不良反应。方法　回顾性分析北京积水潭医院血液科2019年10月-2020年6月接受达雷妥尤单抗治疗的9例复发/难治性多发性骨髓瘤患者临床资料,随访分析疗效及不良反应。结果　9例复发/难治性多发性骨髓瘤患者中7例可进行疗效评估,其中完全缓解（CR）2例（28.6%）,非常好的部分缓解（VGPR）2例（28.6%）,部分缓解（PR）1例（14.3%）,微小缓解（MR）1例（14.3%）,疾病稳定（SD）1例（14.3%）,总体缓解率（ORR）71.4%（5/7）。常见的不良反应为血小板减少、中性粒细胞减少、淋巴细胞减少〔3~4级发生率分别为33.3%（3/9）、33.3（3/9）和55.6%（5/9）〕;输液相关不良反应发生率为44.4%（4/9）。结论　达雷妥尤单抗治疗复发/难治性多发性骨髓瘤具有较好的临床疗效、安全性好。     

含达雷妥尤单抗方案巩固和维持治疗高龄高危初治多发性骨髓瘤1例并文献复习

目的 观察达雷妥尤单抗联合来那度胺及地塞米松(DRd)方案巩固治疗序贯达雷妥尤单抗和来那度胺两药维持治疗1例高龄高危初治多发性骨髓瘤患者的疗效、生存时间和不良反应。方法 回顾分析广州市第一人民医院老年病科血液肿瘤科2019年3月收治的1例高龄高危初治多发性骨髓瘤患者的临床资料，并复习相关最新文献。结果 患者应用伊沙佐米、来那度胺和地塞米松方案诱导治疗13疗程后只达到部分缓解的疗效，未能进一步缓解，且不良反应多且严重，后改为DRd方案巩固治疗2疗程后，达到完全缓解，继续使用达雷妥尤单抗联合来那度胺两药维持治疗，不良反应少，至随访结束总生存期和无进展生存期均为35个月。结论 含达雷妥尤单抗方案巩固和维持治疗可能会改善高龄高危初治多发性骨髓瘤患者的预后，延长生存时间，耐受性好。     

达雷妥尤单抗治疗复发难治性多发性骨髓瘤疗效及对患者骨髓液CD38水平的影响

【摘要】 目的 探讨达雷妥尤单抗治疗复发难治性多发性骨髓瘤（MM）的疗效及对患者骨髓液CD38水平的影响。 方法 选取2019年7月～2020年9月我院收治的115例复发难治性MM患者,随机分为研究组64例和对照组51例。对照组采用BCD方案（硼替佐米+环磷酰胺+地塞米松）或PAD方案（硼替佐米+阿霉素+地塞米松）,研究组在此基础上给予达雷妥尤单抗,均8周为1个疗程。比较两组的临床疗效、治疗前后的骨髓液CD38水平、生存分析以及不良反应。 结果 治疗后,研究组总体缓解率76.56%高于对照组的52.94% (P＜0.05);研究组CD38阳性表达率以及CD38浆细胞表面Notch1表达水平低于对照组 (P＜0.05);研究组中位无进展生存期8.5个月（2.5～15个月）长于对照组的6.0个月（1.4～15个月） (P＜0.05);两组不良反应发生率比较差异无统计学意义（P＞0.05）。 结论 复发难治性多发性骨髓瘤在常规治疗的基础上联合达雷妥尤单抗可提高总体缓解率,延长无进展生存期,耐受性较好,可增加患者临床获益。     

达雷妥尤单抗应用于硼替佐米治疗后复发多发性骨髓瘤的效果观察

目的 探讨达雷妥尤单抗应用于硼替佐米治疗后复发多发性骨髓瘤的效果。方法 选取河南科技大学第一附属医院血液科2018年5月～2021年5月收治的72例复发多发性骨髓瘤患者,随机分为观察和对照两组,各36例。对照组采取硼替佐米+阿霉素+地塞米松(PAD)方案治疗,观察组在对照组的基础上给予达雷妥尤单抗治疗。比较两组患者治疗后临床疗效及不良反应。结果 观察组完全缓解(CR)12例、非常好的部分缓解(VGPR)10例、部分缓解(PR)6例、疾病稳定(SD)7例、疾病进展(ORR)1例,总缓解率(ORR)28例(77.78%),对照组CR5例、VGPR7例、PR8例、SD7例、PD9例、ORR20例(55.56%),观察组ORR显著高于对照组(P<0.05);观察组发生感染5例、中重度疼痛3例、胃肠系统反应2例、骨髓抑制2例,不良反应总发生12例(33.33%),对照组发生感染5例、骨髓抑制3例、中重度疼痛2例、胃肠系统反应4例,不良反应总发生15例(41.67%),两组患者不良反应总发生率比较,无统计学意义(P>0.05)。结论 采用达雷妥尤单抗治疗多发性骨髓瘤能有效提高总缓解率,...     

含达雷妥尤单抗方案在复发难治多发性骨髓瘤患者中的疗效与安全性分析

目的探讨含达雷妥尤单抗的方案在复发难治多发性骨髓瘤(RRMM)患者中的疗效与安全性。方法回顾性分析2020年12月至2023年11月青岛市市立医院收治的42例RRMM患者的临床资料, 其中男26例, 女16例, 年龄为59(47, 82)岁。根据患者使用达雷妥尤单抗疗程数不同分为3组:长疗程组(≥9个疗程, n=21)、中疗程组(7～8个疗程, n=12)、短疗程组(≤6个疗程, n=9)。随访截至2023年11月10日, 随访时间为15.6(6.0, 34.0)个月。患者完成至少2个疗程的治疗后进行疗效评估, 包括严格意义上的完全缓解(sCR)、完全缓解(CR)、非常好的部分缓解(VGPR)、部分缓解(PR)、微小缓解(MR)、疾病稳定(SD)和疾病进展(PD)。统计分析患者基本临床特征、治疗的总有效率以及不良反应。采用Kaplan-Meier法绘制生存曲线, 比较不同疗程数组间无进展生存时间(PFS)的差异。结果 42例患者中, 15例(35.7%)合并髓外病变或浆细胞白血病, 7例(16.6%)合并淀粉样变性, 18例(42.9%)合并肾功能不全。Mayo分期中, 骨髓瘤细胞遗传...     

CD38单抗治疗多发性骨髓瘤配血方法探讨

目的 分析应用达雷妥尤单抗治疗的难治性、复发性多发性骨髓瘤患者的输血效果,寻求安全的配血方法。方法 查阅胜利油田中心医院2例多发性骨髓瘤患者应用达雷妥尤单抗治疗前后输血相容性检测结果和患者病历,分析输注凝聚胺配血相合ABO及Rh同型血液的输血效果。结果 治疗前患者意外抗体筛查及交叉配血均阴性,治疗后均阳性（+～++凝集）,微柱法交叉配血主侧不相合（+～++凝集）,次侧相合。0.2 mol/L的二硫苏醣醇（DTT）溶液处理筛选细胞和供血者红细胞后抗筛阴性配血相合,凝聚胺方法均阴性。输注凝聚胺相合红细胞后,2例患者红细胞输注有效率为60.0%和52.6%,部分有效率为40.0%和47.4%,效果显著。结论 单抗治疗患者排除同种抗体情况下输注凝聚胺配血相合Rh同型血液是有效的。     

达雷妥尤单抗治疗复发难治多发性骨髓瘤的成本效果分析

目的 评价达雷妥尤单抗联合硼替佐米、地塞米松(D-Vd)在治疗复发或难治性多发性骨髓瘤患者(RRMM),相比硼替佐米和地塞米松(Vd)治疗RRMM的成本效果性.方法 采用基于中国患者的LEPUS临床试验所获数据(D-Vd:141名患者;Vd:70名患者),建立患者无进展状态、进展状态和死亡状态的疾病发展过程Markov...     

1例暴发性复发-缓解型多发性硬化症患者脑脊液和外周血液的临床稳态和有效B淋巴细胞衰竭

背景:抗CD20单克隆抗体利妥昔单抗能有效耗尽B淋巴细胞,并已成功用于治疗外周神经系统免疫介导性疾病。最近有利妥昔单抗对原发进行性多发性硬化症(M S)患者脑脊液中B淋巴细胞有限作用的报道。目的:明确利妥昔单抗对复发-缓解型M S患者临床、磁共振成像和免疫学变量的影响。设计:用利妥昔单抗治疗1例复发-缓解型M S患者,反复检查患者的临床和M RI表现。在利妥昔单抗治疗前、治疗期间和治疗后分别采用流式细胞仪分析外周血液和脑脊液中的B淋巴细胞数。结果:利妥昔单抗单一治疗使患者的临床症状显著改善,M RI中的炎性替代标记物也减少…     

利妥昔单抗联合挽救化疗治疗复发或难治弥漫大B细胞性非霍奇金淋巴瘤的长期随访结果

目的 旨在评价利妥昔单抗联合挽救化疗治疗复发难治弥漫大B细胞性非霍奇金淋巴瘤(DLBCL)的疗效和不良反应.方法 中山大学肿瘤防治中心1998年10月至2009年11月使用利妥昔单抗共治疗69例复发难治DLBCL患者,其中男性40例,女性29例,中位年龄51.5岁(17-82岁).所有患者均经病理确诊,并接受利妥昔单抗联合常用挽救化疗,化疗方案主要包括EPOCH、ICE、DHAP、GEMOX及GDP等.27例在初治时曾使用过利妥昔单抗,其余则在复发难治时与联合挽救化疗首次联合使用.结果 69例患者中有64例可以评价疗效,5例未进行疗效评价.总体客观有效率为73.4%(47/64),完全缓解率为45.3%(29/47).13例患者在挽救方案获得缓解后接受自体造血干细胞支持下的超大剂量化疗(AHSCT/HDT);主要不良反应为骨髓抑制、乏力及胃肠道反应.与利妥昔单抗相关的不良反应主要有寒战、发热和乏力.随访截止至2009年11月13日,中位随访40.6(3.7～179.9)月,有28例患者死于肿瘤进展,2例死于Ⅳ度骨髓抑制并严重感染,其余患者仍健在.中位生存时间为51.6月(3.7～179.9),第1、3和5年生存率分别为92%、62%和37%.初治未使用利妥昔单抗患者的生存期较初治曾使用利妥昔单抗组的患者长,两组的第1、3年生存率分别为97.4%,73.5%和83.1%,42.8%(P=0.001).GCB型较非GCB型复发难治DLBCL有明显生存优势,5年生存率分别为42.3%和21.4%(P=0.005).结论 利妥昔单抗联合挽救化疗治疗DLBCL的疗效较好,不良反应可以耐受,结果与文献报道相似.     

贝林妥欧单抗治疗成人复发或难治性前体B细胞急性淋巴细胞白血病的安全用药实践经验

目的 总结贝林妥欧单抗治疗成人复发或难治性前体B细胞急性淋巴细胞白血病(R/R BCP-ALL)的安全用药实践经验。方法 回顾性分析使用贝林妥欧单抗治疗的9例R/R BCP-ALL患者的临床资料，记录患者用药情况、输注中断情况、不良反应发生情况及治疗结局。结果 9例患者共接受446次贝林妥欧单抗静脉输注，其中由疾病原因导致用药提前结束4次，实际按规定剂量完成用药442次。发生计划外中断输注6次(1.36%,6/442),输注中断原因包括输液泵报警、输液器脱出、药液未能及时配送到病房。9例患者均发生细胞因子释放综合征，严重不良事件2例，其中1例为肺部感染，1例为听力受损，均未发生神经系统毒性和危及生命的不良反应。随访时间0～20个月，中位随访13个月，1例患者保持完全缓解，4例患者行造血干细胞移植术(2例死亡),2例患者行姑息性化疗后死亡，2例患者回当地医院治疗后失访。结论 贝林妥欧单抗药物配置过程复杂，持续输注要求严格，不良反应发生率高，要求护理人员具备较高的静脉导管维护技术和早期发现、识别不良反应的能力。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.