真实世界伊沙佐米治疗多发性骨髓瘤疗效与安全性研究

目的 评估真实世界伊沙佐米治疗多发性骨髓瘤（MM）的疗效和安全性。方法 回顾性分析2019年1月至2021年1月来自中国贫血东部协作组单位（无锡市人民医院等）伊沙佐米治疗72例MM患者的血液学、细胞遗传学及疗效、安全性等数据。结果 难治/复发MM(RRMM)患者接受伊沙佐米的中位治疗周期为6.0(3.0,7.0)个，总体有效率（ORR）为56.5%；新诊断MM(NDMM)患者中位治疗周期为4.5(4.0,9.5)个，总体有效率为85.8%；转换维持治疗组患者中位治疗周期为5.0(3.0,8.0)个，其中25.8%的患者缓解程度加深；不良事件（AEs）的总体发生率为26.5%。结论在真实世界中，伊沙佐米对RRMM、NDMM或是维持转换MM患者，具有良好的疗效和安全性。     

伊沙佐米治疗难治复发多发性骨髓瘤临床疗效及相关毒副反应研究

目的:探讨伊沙佐米治疗难治复发多发性骨髓瘤的临床疗效及相关毒副反应。方法:2018-08-2019-08我院对15例难治复发多发性骨髓瘤患者行以伊沙佐米为基础化疗,随访分析治疗后反应率及相关毒副反应,并对相关临床指标进行分析。结果:经以伊沙佐米为基础诱导化疗诱导治疗后2例(13.3%)患者达到完全缓解,3例(20.0%)达到部分缓解,总有效率为33.3%。在治疗前,治疗无效组的血肌酐及β2微球蛋白浓度明显高于治疗有效组(均P0.05)。伊沙佐米为基础诱导化疗常见的毒副反应包括中细粒细胞减少5例,血小板减少3例,血红蛋白下降3例,皮疹2例,肺部感染3例,肝功能异常1例,恶心5例,乏力6例。结论:伊沙佐米对部分难治复发多发性骨髓瘤安全有效,是难治复发多发性骨髓瘤的治疗新选择。     

硼替佐米为主治疗多发性骨髓瘤的疗效与安全性临床观察

目的:研究以硼替佐米为主的联合化疗对多发性骨髓瘤(MM)的疗效及其不良反应。方法:回顾性分析52例MM患者,其中42例接受以硼替佐米为主的联合化疗方案:初发MM 31例,复发难治MM 11例;轻链型12例,非轻链型30例;肾功能正常27例,肾功能损害15例;另外10例接受传统型(含长春新碱+蒽环类+地塞米松)化疗方案。比较硼替佐米初治组与传统化疗组,硼替佐米治疗组中轻链型与非轻链型、肾功功能正常者与肾功能损害者的疗效。同时观察42例硼替佐米治疗患者的不良反应。结果:硼替佐米初治组总有效率(ORR)和完全缓解(CR)+非常好的部分缓解(VGPR)率分别为87.10%(27/31)和64.52%(20/31),分别优于传统化疗组的20.00%(2/10)和10.00%(1/10),2组比较均差异有统计学意义(均P0.05)。硼替佐米治疗组中非轻链型患者的ORR和CR+VGPR率分别为76.67%(23/30)和56.67%(17/30),分别高于轻链型患者的75.00%(9/12)和50.00%(6/12),但2组比较差异无统计学意义;肾功能正常患者的ORR和CR+VGPR率分别为77.78%(21/27)和59.26%(16/27),分别高于肾功能损害者的73.33(11/15)和46.67%(7/15),但2组比较差异亦无统计学意义。接受硼替佐米治疗的42例患者中,不良反应主要为乏力(28.57%、12/42)和周围神经炎(35.71%、15/42)。在给药途径方面,硼替佐米静脉给药组乏力和周围神经炎的发生率,均分别高于硼替佐米皮下注射组(42.86%∶14.28%,52.38%∶19.05%,均P0.05)。结论:以硼替佐米为主的方案治疗初发MM疗效优于传统化疗方案,肾功能不全患者可以安全使用。硼替佐米的主要不良反应为乏力和周围神经炎,不良反应可以耐受。硼替佐米皮下注射给药可以有效减少不良反应,安全性相对较高。     

硼替佐米联合地塞米松治疗多发性骨髓瘤临床研究

目的观察硼替佐米联合地塞米松(PD)在多发性骨髓瘤(MM)中的应用。方法 2008年2月至2010年4月北京积水潭医院36例MM患者接受PD治疗。以同期46例VADT化疗的MM患者做为对照。分析病情转归及不良反应。结果 (1)PD用于初治和复发和(或)难治MM患者疗效均显著。初治组治疗有效率85.7%(18/21);复发和(或)难治组的有效率为80.0%(12/15);总有效率为83.3%(30/36)。PD与VADT治疗初治MM的有效率差异无统计学意义(85.7%对78.1%,P=0.740),PD治疗复发和(或)难治MM的有效率明显高于VADT组(80.0%对42.9%,P=0.039)。PD起效快,治疗有效的患者均在1个疗程后达PR;63.9%患者在3个疗程内达到VGPR以上缓解,优于VADT组的30.4%。(2)PD不良反应主要有乏力、周围神经病变及血小板减少等。PD治疗初治MM较复发和(或)难治MM不良反应小,耐受性好,更能坚持长期化疗以获得最大缓解。(3)PD治疗的MM患者骨痛缓解快,全身骨密度增高较VADT组更显著[(1.138±0.102)g/cm2对(1.053±0.137)g/cm2,P=0.039)]。结论硼替佐米联合地塞米松治疗MM缓解率高,可首选用于治疗初治及复发和(或)难治MM。     

硼替佐米为主的联合方案治疗初治多发性骨髓瘤

目的 回顾性比较分析硼替佐米为主方案(VD/VT)与长春新碱联合阿霉素和地塞米松(VAD)方案治疗初治多发性骨髓瘤(MM)的疗效及不良反应.方法 18例初治MM患者采用硼替佐米1.0 mg/m2或1.3 mg/m2,1、4、8、11 d给药;12例联合地塞米松20～40mg,1～4 d;6例联合沙立度胺100mg/d,21d为一疗程.24例MM患者采用VAD方案.结果 硼替佐米组总反应率88.9%(16/18),完全缓解或接近完全缓解率38.9%(7/18),显著优于VAD组,分别为41.7%,4.2%.硼替佐米组主要的不良反应依次为血液系统毒性,胃肠道反应和周围神经病变.VAD组主要不良反应为感染、脱发及静脉炎.结论 硼替佐米为主的联合化疗在初治MM中疗效显著优于VAD组,尤其在高危人群如严重骨质破坏、肾功能不全及不良染色体表现的患者,缓解率高,毒副作用轻,应优先考虑使用.     

硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤近期疗效分析

目的:分析硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤(MM)患者的临床疗效和不良反应.方法:初治MM患者11例,复发、难治MM患者7例均采用VD方案化疗:硼替佐米1.0～1.3 mg/m2第1、4、8和11天快速静脉注射,地塞米松20 mg第1～4天(7例复发难治予地塞米松40 mg)静脉滴注,3周为1疗程,所...     

真实世界国产硼替佐米治疗初诊多发性骨髓瘤疗效评价

目的:探讨国产硼替佐米治疗初诊多发性骨髓瘤的有效性及安全性。方法:回顾性分析2017年7月—2020年8月我院接受以国产硼替佐米为基础的联合化疗方案治疗的初诊多发性骨髓瘤患者74例,其中BD方案化疗47例,BCD方案化疗11例,BAD方案化疗16例,每2个疗程后行有效性及安全性评估。结果:截至2020年11月,4例患者出现失访,部分患者因经济原因、依从性差等原因未能返院治疗。共有74例患者完成2个疗程,治疗总反应率(ORR)为68.9%(51/74)。58例患者完成4个疗程,ORR为77.6%(45/58)。32例患者完成6个疗程治疗,ORR为81.3%(26/32)。13例患者完成8个疗程治疗,ORR为92.3%(12/13)。三药联合的BCD、BAD方案治疗2、4个疗程的ORR优于两药联合的BD方案,差异有统计学意义(P0.05)。治疗中出现的不良反应主要为白细胞减少、血小板减少、周围神经病变、胃肠道反应、带状疱疹病毒感染等,多为Ⅰ～Ⅲ级,未见Ⅳ级血液学及非血液学不良反应。三药联合组白细胞减少发生率高于两药组(33.3%vs 12.8%,P0.05),其余不良反应差异无统计学意义。结论:在真实世界中,以国产硼替佐米为基础的联合化疗方案治疗初诊多发性骨髓瘤患者可取得较好的临床疗效,安全可靠,尚需要大样本临床数据进行长期追踪随访来验证其远期疗效。     

硼替佐米和沙利度胺为主的化疗方案对伴有肾功能不全的多发性骨髓瘤患者的疗效比较

目的:观察以硼替佐米为主和沙利度胺为主的化疗方案治疗伴有肾功能不全的多发性骨髓瘤(MM)患者的疗效,探讨对伴有肾功能不全的MM治疗的最佳方案.方法:40例伴有肾功能不全的MM患者,其中初治20例,复发(难治)20例.选择20例使用以硼替佐米为主的化疗方案作为试验组,以同期20例接受沙利度胺为基础的联合化疗方案治疗的MM...     

硼替佐米为主的化疗方案治疗多发性骨髓瘤50例临床分析

目的：研究硼替佐米（万珂）为主的化疗方案治疗多发性骨髓瘤（MM）的疗效和安全性。方法：收集近4年来我科住院和随访的MM患者91例的临床资料,其中50例接受万珂为主化疗方案（VDT组）;41例接受传统化疗方案（VADT）。分析并比较2组患者的年龄、性别、β2-微球蛋白值、白蛋白值和2组的缓解率及不良反应。疗效评价按照欧洲骨髓移植协作组（EBMT）标准。结果：2组患者的年龄、性别、疾病分期无明显差异。中位随访20个月,发现VDT组50例患者总体反应率为88%,平均2个疗程即起效。其中初治患者CR＋nCR率明显优于同组复发难治患者以及传统方案治疗组,且初治患者的总缓解率在VDT组与VADT组中存在显著差异。VDT组不良反应以周围神经病变和血小板减少为常见,经对症治疗均可缓解。结论：万珂为主的化疗方案治疗初治和复发难治MM患者,起效快,其中初治患者CR＋nCR率及总缓解率更高,其不良反应可耐受。对有不良核型和IgD型MM患者,如何提高疗效尚待研究。     

硼替佐米联合地塞米松方案治疗多发性骨髓瘤的临床疗效

目的探讨硼替佐米联合地塞米松方案治疗多发性骨髓瘤(MM)的临床疗效。方法选取该院诊治的51例MM患者作为研究对象,按治疗方案分为两组,观察组31例采用硼替佐米联合地塞米松治疗,对照组20例接受长春新碱、吡柔比星、地塞米松和左旋苯丙氨酸氮芥(马法兰)治疗。比较两组患者临床疗效、不良反应等情况。结果观察组总有效率为80.65%(25/31),对照组总有效率65.00%(13/20)差异显著(P<0.05);观察组对初治病例有效率为86.36%(19/22),难治复发病例有效率为66.67%(6/9);对肾功能正常病例有效率为90.00%(18/20),对肾功能损害病例的有效率为63.64%(7/11)差异显著(P<0.05);观察组总不良反应发生率为51.61%,对照组为65.00%,差异显著(P<0.05)。结论硼替佐米联合地塞米松治疗MM有效率高,不良反应轻,对初治患者疗效最显著,值得推广应用。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.