Jing Liu

Background: Extrachromosomal circular DNA (EccDNA) is widespread in various heterogeneous tumors and closely associated with tumor resistance and progression.

Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota–host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.

Background: Multiple myeloma (MM) is a malignant and incurable disease. Currently, chemotherapy is the primary approach for the treatment of MM. Bortezomib (BTZ) is a breakthrough drug for MM, significantly improving patient survival. However, BTZ can interrupt the treatment due to its serious side effects. Therefore, developing novel therapeutics for MM is essential. Herein, an innovative nanoparticle-based drug delivery system P-R@Ni₃P-BTZ is designed and constructed to treat MM. The present study investigated the feasibility, effectiveness, and safety of P-R@Ni₃P-BTZ in vitro and in vivo. Results: Trinickel monophosphide nanoparticles (Ni₃P NPs) are spherical porous hollow materials with photothermal performance. As a novel scaffold, Ni₃P integrates photothermal therapy (PTT) with chemotherapy by loading BTZ (Ni₃P-BTZ). In addition, Ni₃P-BTZ is wrapped by a thin layer of the red blood cell membrane (Rm) to form R@Ni₃P-BTZ, which confers the enhanced permeability and retention (EPR) effect and reduces immunogenicity. Finally, CD38-targeting peptide P is inserted into Rm via DSPE-PEG2000-P to precisely target MM cells (P-R@Ni₃P-BTZ). In vitro and in vivo, it proved that P-R@Ni₃P-BTZ has excellent targeting ability to CD38 + MM cells and is highly effective in killing MM cells. P-R@Ni₃P-BTZ significantly induces the accumulation of intracellular reactive oxygen species (ROS) levels and increases apoptosis of MM cells, which underlies the primary mechanism of antitumor effects. In addition, in vitro and in vivo experiments proved that P-R@Ni₃P possesses good biocompatibility and biosafety. Conclusions: These findings suggested that P-R@Ni₃P-BTZ nanodrug delivery system is a promising CD38 targeting chemotherapy and PTT nanocomposites, which is a specific and efficient MM therapeutic method.

Objective: To understand the infection characteristics and risk factors for infection by analyzing multicenter clinical data of newly diagnosed multiple myeloma (NDMM) patients.Methods: This study reviewed 564 NDMM patients from 2 large tertiary hospitals from January 2018 to December 2021, of whom 395 comprised the training set and 169 comprised the validation set. Thirty-eight variables from first admission records were collected, including patient demographic characteristics, clinical scores and characteristics, laboratory indicators, complications, and medication history, and key variables were screened using the Lasso method. Multiple machine learning algorithms were compared, and the best performing algorithm was used to build a machine learning prediction model. The model performance was evaluated using the AUC, accuracy, and Youden’s index. Finally, the SHAP package was used to assess two cases and demonstrate the application of the model.Results: In this study, 15 important key variables were selected, namely, age, ECOG, osteolytic disruption, VCD, neutrophils, lymphocytes, monocytes, hemoglobin, platelets, albumin, creatinine, lactate dehydrogenase, affected globulin, β2 microglobulin, and preventive medicine. The predictive performance of the XGBoost model was significantly better than that of the other models (AUROC: 0.8664), and it also performed well for the expected dataset (accuracy: 68.64%).Conclusion: A machine learning algorithm was used to establish an infection prediction model for NDMM patients that was simple, convenient, validated, and performed well in reducing the incidence of infection and improving the prognosis of patients.

国内多发性骨髓瘤(multiple myeloma，MM)临床大数据较少，本研究旨在分析湖南省多中心1年期间新诊断多发性骨髓瘤(newly diagnosed multiple myeloma，NDMM)患者的临床资料，了解湖南省MM患者真实的临床特征和诊疗情况，加强对MM规范化诊疗流程和诊疗方案的认识。 收集湖南省12家大型综合性医院2019年1月1日至12月31日收治的共529例NDMM患者的临床资料，包括基线资料、治疗方案、疗程和不良反应等。采用SPSS 21.0统计软件分析患者的临床特征、治疗情况及安全性。 529例NDMM患者确诊年龄33~90(中位数64)岁，男女比为1.38꞉1；临床特征占比从高到低依次为骨痛(77.7%)、贫血(66.8%)、肾功能不全(40.6%)、高钙血症(15.1%)。分型：IgG型46.5%，IgA型24.6%，IgD型2.6%，IgM型0.8%，轻链型15.7%，双克隆型3.0%，不分泌0.6%，缺失6.2%。DS(Durie-Salmon)分期I期、II期、III期分别为4.5%、10.6%、77.3%，缺失40例(7.6%)；国际分期系统(International Staging System，ISS)分期I期、II、III期分别为10.4%、24.4%、47.6%，缺失93例(17.6%)；修订的国际分期系统(Revised International Staging System，R-ISS)分期I期、II、III期分别为5.5%、27.0%、23.1%，缺失235例(44.4%)，其中中南大学湘雅三医院单中心98例NDMM患者中DS分期缺失2.0%，ISS分期缺失12.3%，R-ISS分期缺失12.3%。治疗情况：529例患者中475例接受治疗，接受治疗率为89.8%；67.4%的患者能规范完成4个疗程诱导阶段的化学治疗(以下简称化疗)，其中90.3%的患者接受1次以上以蛋白酶体抑制剂为基础的化疗方案，67.2%接受1次以上以免疫调节剂为基础的化疗方案，59.8%的患者接受1次以上含蛋白酶体抑制剂与免疫调节剂的联合化疗方案。疗效：4个疗程组总缓解率(overall response rate，ORR)及高质量缓解率(high quality response rate，HQR)均优于2个疗程组(ORR为85% vs 65%，P=0.006；HQR为68.3% vs 24.0%，PP=0.035)。治疗期间出现的不良反应：血液学毒性17.5%、外周神经病变24.8%、胃肠道不良反应23.8%、肺部感染25.9%、带状疱疹4.6%、静脉血栓1.7%。 2019年期间湖南省NDMM的漏诊率较高，中位确诊年龄较大；诊断精准度不高，特别是在分期及危险分层上各医疗中心差异较大，将近一半的NDMM患者诊断时没有作出R-ISS分期；细胞遗传学数据缺失，需在后续研究中跟进。NDMM患者就诊时骨痛、贫血症状占比较高；接受治疗的患者中蛋白酶体抑制剂和/或免疫调节剂化疗方案使用率较高，但各医疗中心差距明显，规范化治疗尚待加强；化疗期间的安全性总体可控。

Background: Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments.

Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM prognosis and advance potential therapeutic targets.