多发性骨髓瘤中表观遗传学修饰的研究进展北大核心

多发性骨髓瘤(multiple myeloma,MM)是一种病因不明,目前仍无法治愈的恶性血液系统性疾病。研究显示MM是一种复杂的表观遗传学修饰所驱动的恶性肿瘤,表观遗传学修饰是改变MM发病进展的重要机制,并影响治疗及预后。本文将对表观遗传学异常调控在MM的发生发展过程中的作用及相关耐药机制和治疗的现状进行综述。     

FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m6A-YTHDF2-dependent manner

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Social cognitive correlates of device-measured and self-reported physical activity in Black and White individuals with multiple sclerosis

BackgroundThere is increasing research interest regarding physical activity behavior among persons with multiple sclerosis (MS), yet there is little known about physical activity and its correlates in Black persons with MS.ObjectiveThis cross-sectional study assessed associations among social cognitive theory (SCT) variables and device-measured and self-reported physical activity in samples of Black and White persons with MS.MethodsParticipants included 67 Black and 141 White persons with MS who wore an ActiGraph accelerometer on a belt around the waist measuring moderate-to-vigorous physical activity (MVPA) for seven days and completed a battery of questionnaires. Questionnaires included demographic and clinical characteristics, leisure-time exercise, exercise self-efficacy, overcoming barriers self-efficacy, function, social support, exercise outcome expectations, and goal setting and planning.ResultsBlack participants with MS engaged in significantly less MVPA, but not sedentary behavior or light physical activity, than the White participants with MS. Black participants further had significantly lower levels of exercise self-efficacy and outcome expectations than the White sample. All SCT correlates were significantly correlated with self-reported physical activity, but only exercise and barriers self-efficacy, perceived function, and exercise goal setting were associated with device-measured MVPA. The difference in physical activity between Black and White participants with MS was accounted for by differences in exercise self-efficacy and outcome expectations.ConclusionsResearchers should consider developing behavioral interventions that target exercise self-efficacy and outcome expectations as SCT variables for increasing physical activity in Black persons with MS.     

Pentobarbital overdose: A case of contract killing

Suicides by pentobarbital overdose have increased since about 2012, which appear to be influenced by technical information on active euthanasia that has spread over the Internet. We encountered a pentobarbital poisoning case of a patient with amyotrophic lateral sclerosis. A caregiver found the patient unconscious immediately after two visitors left the room. The patient was immediately transferred to the emergency hospital but eventually declared dead. A fatal concentration of pentobarbital was detected in peripheral blood samples collected in the emergency hospital and during autopsy (53.8 μg/mL and 29.4 μg/mL, respectively). Because the ratios of pentobarbital concentrations between the gastric contents and peripheral blood were 35 and 29 in the hospital and autopsy samples, respectively, it is likely that pentobarbital was administered via the gastrostomy tube. The patient had contacted the visitors through social media. Although the patient had requested the doctor perform active euthanasia and expressed a desire to end their life on social media, nobody had noticed the plan to commit suicide.     

Method’s corner: Allergist’s guide to network meta-analysis

Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.     

多指标综合加权评分法优选复方夏枯草洗剂提取工艺研究

[目的] 优选复方夏枯草洗剂的提取工艺。[方法] 采用L₉（3⁴）正交设计，以迷迭香酸、丹酚酸B的含量及出膏率的综合评分为指标，考察料液比、提取时间、提取次数对提取效果的影响，优选复方夏枯草洗剂的最佳提取工艺。[结果] 根据综合评分的结果，优选出最佳提取工艺为加8倍水，提取3次，每次0.5 h。[结论] 该工艺准确可靠，可行性好。     

B-cell maturation antigen-specific chimeric antigen receptor T cells for multiple myeloma: Clinical experience and future perspectives

Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long-term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B-cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA-targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA-specific CAR-T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA-directed CAR-T cells and discuss potential future perspective for this promising treatment approach in MM.     

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.