Erythropoiesis occurs first in the yolk sac as a transit \"primitive\" form, then is gradually replaced by the \"definitive\" form in the fetal liver (FL) during fetal development and in the bone marrow (BM) postnatally. While it is well known that differences exist between primitive and definitive erythropoiesis, the similarities and differences between FL and BM definitive erythropoiesis have not been studied. Here we performed comprehensive comparisons of erythroid progenitors and precursors at all maturational stages sorted from E16.5 FL and adult BM. We found that FL cells at all maturational stages were larger than their BM counterparts. We further found that FL BFU-E cells divided at a faster rate and underwent more cell divisions than BM BFU-E. Transcriptome comparison revealed that genes with increased expression in FL BFU-Es were enriched in cell division. Interestingly, the expression levels of glucocorticoid receptor Nr3c1, Myc and Myc downstream target Ccna2 were significantly higher in FL BFU-Es, indicating the role of the Nr3c1-Myc-Ccna2 axis in the enhanced proliferation/cell division of FL BFU-E cells. At the CFU-E stage, the expression of genes associated with hemoglobin biosynthesis were much higher in FL CFU-Es, indicating more hemoglobin production. During terminal erythropoiesis, overall temporal patterns in gene expression were conserved between the FL and BM. While biological processes related to translation, the tricarboxylic acid cycle and hypoxia response were upregulated in FL erythroblasts, those related to antiviral signal pathway were upregulated in BM erythroblasts. Our findings uncovered previously unrecognized differences between FL and BM definitive erythropoiesis and provide novel insights into erythropoiesis.

Nasopharyngeal carcinoma with bone marrow metastasis presents a rare and challenging clinical scenario associated with exceedingly poor prognosis. While standard treatment regimens offer limited efficacy and tolerability in such cases, individualized approaches are increasingly necessary. We present the case of a 64-year-old male diagnosed with recurrent nonkeratinizing undifferentiated nasopharyngeal carcinoma with extensive bone marrow metastasis (rTxN0M1). Treatment was initiated with immunotherapy-based combination therapy, consisting of pembrolizumab and low-dose cisplatin, which resulted in an initial response. Subsequently, there was a transition to standard-dose nab-paclitaxel-cisplatin chemotherapy in combination with pembrolizumab, followed by maintenance therapy with pembrolizumab plus fruquintinib. The patient achieved a sustained response with renormalization of tumor markers, imaging findings, and bone biopsies, resulting in complete remission. This case highlights the successful management of nasopharyngeal carcinoma with extensive bone marrow metastasis through an individualized treatment approach incorporating immunotherapy.

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.

Objective: To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed. Results: A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages (P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams (P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 (P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and β(2)-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and β(2)-microglobulin at the initial diagnosis (P<0.05) ; lower HGB level (P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ (P=0.034) . Conclusion: In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, β(2)-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.
目的： 探究初诊多发性骨髓瘤（NDMM）患者骨髓多克隆浆细胞占比（pPC%）与临床特征的相关性。 方法： 回顾性分析2018年1月至2023年1月在华中科技大学同济医学院附属同济医院收治的317例NDMM患者，纳入患者均有明确的pPC%结果。分析pPC%与临床特征的关系。 结果： 共纳入317例患者，其中男180例，女137例，中位确诊年龄61（26～91）岁，≥60岁患者占55.8%。NDMM患者骨髓pPC%在各DS分期、ISS分期、R-ISS分期组差异均有统计学意义（P值分别为0.002、0.010、0.049），而不同的FISH危险分层患者pPC%差异无统计学意义（P＝0.971）。NDMM患者pPC%与患者初诊时HGB呈正相关（r＝0.211，P<0.01）；与血钙、血肌酐、单克隆免疫球蛋白（M蛋白）定量、β(2)微球蛋白水平呈负相关（r分别为-0.141、-0.120、-0.181、-0.207，P值为0.012、0.033、0.004、0.002）。与pPC%≥2.5%患者相比，pPC%<2.5%组患者初诊时受累轻链、血钙、血肌酐、M蛋白和β(2)微球蛋白水平明显升高（P值均<0.05），HGB降低（P<0.001），ISS分期Ⅲ期比例更高（P＝0.034）。 结论： NDMM患者pPC%与良好预后的临床特征相关，包括更高的HGB，更低的血钙、血肌酐、M蛋白定量、β(2)微球蛋白，受累轻链，更低的晚期疾病占比（DS分期、ISS分期Ⅲ期），在临床特点上表现为肿瘤负荷较小。.

Bone marrow biopsy is one of the important means of hematopathological diagnosis, which has decisive diagnostic significance for various benign and malignant lymphohematopoietic system diseases. Its diagnostic value includes morphological observation, immunohistochemistry, genetics, and molecular biology testing. Owing to the unique nature of bone marrow biopsy, decalcification is an essential step in the pre-treatment process. Its purpose is to remove calcium from bone tissue, preserve intact collagen fiber components, facilitate tissue sectioning, and prevent tissue detachment during staining. If bone marrow biopsy lacks sufficient decalcification, preparing a section is difficult. Conversely, if decalcification is excessive, it can seriously disrupt tissue antigen activity. Therefore, a decalcification method with high decalcification efficiency and mild antigen damage is essential for bone marrow biopsy. This article introduces a bone marrow biopsy tissue decalcification method with high efficiency and less antigen loss: decalcification is performed at room temperature with 12% formic acid and 8% hydrochloric acid decalcification solution on a shaker.
骨髓活检是血液病理诊断的重要手段之一，对于多种良、恶性淋巴造血系统疾病均具有决定性的诊断意义，其诊断价值包括形态学观察，以及免疫组化、遗传学和分子生物学等辅助检测。由于骨髓活检组织本身的特殊性，脱钙是前期处理过程中必不可少的环节，其目的是将骨组织中钙盐去掉，保留完整的胶原纤维成分，以利于组织切片以及避免染色时掉片。如果骨髓活检脱钙不充分，则难以制片，但如果脱钙过度，又会严重破坏组织抗原活性，因此，一种脱钙效率高且抗原破坏小的脱钙方法对于临床病理骨髓活检十分重要。本文介绍一种高效且抗原破坏较小的骨髓活检组织脱钙方法：12%甲酸-8%盐酸脱钙液室温摇床脱钙，供广大同仁参考和指正。.

Objective: The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . Methods: This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. Results: ①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM (R(2)=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion: sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.
目的： 探索多发性骨髓瘤（MM）患者骨髓可溶性B细胞成熟抗原（sBCMA）表达对靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T细胞）治疗疗效及安全性的影响。 方法： 以2018年1月至2021年12月接受人源化抗BCMA CAR-T细胞临床试验的29例复发/难治MM（RRMM）患者为研究对象。流式细胞术检测抗BCMA CAR-T细胞治疗前后骨髓sBCMA的表达并进行差异比较。 结果： ①BCMA CAR-T细胞治疗2个月，20例（68.97%）患者获得总体反应（OR），9例患者仅为病情稳定（SD）或微小缓解（MR）。②20例OR组患者骨髓sBCMA表达治疗前高于治疗后[26 926（18 215, 32 488）ng/L对9 968（6 634, 11 459）ng/L，P<0.001]；而MR+SD组患者骨髓sBCMA表达治疗前后差异无统计学意义[41 187（33 816, 47 046）ng/L对33 954（31 569, 36 256）ng/L，P=0.145]；CAR-T细胞治疗前骨髓sBCMA表达OR组低于MR+SD组患者（P=0.005）。③全部29例RRMM患者CAR-T细胞峰值与骨髓sBCMA表达无明显线性相关性（R(2)=0.035，P=0.330）。④sBCMA表达水平与CAR-T细胞治疗不良事件严重程度的相关性：0~1级细胞因子释放综合征（CRS）组（13例）与2~4级CRS组（16例）比较骨髓sBCMA表达差异无统计学意义[32 045（18 742, 40 801）ng/L对29 102（24 679, 38 776）ng/L，P=0.879]；0级免疫效应细胞相关神经毒性综合征（ICANS）组（22例）与1~3级ICANS组（7例）比较骨髓sBCMA表达差异无统计学意义[30 073（19 375, 40 065）ng/L对33 816（22 933, 43 459）ng/L，P=0.763]。 结论： 骨髓sBCMA表达与RRMM患者接受BCMA CAR-T细胞治疗的疗效有关，但与不良事件严重程度无显著相关性。或可作为RRMM患者接受BCMA CAR-T细胞治疗的疗效预测标志物。.

UNASSIGNED: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes.
UNASSIGNED: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration\'s RoB tool. Random-effects models were used for the meta-analysis.
UNASSIGNED: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes.
UNASSIGNED: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

OBJECTIVE: To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping.
METHODS: The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed.
RESULTS: No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity (P > 0.05). At low humidity, there was a statistical difference between the two methods (P < 0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases (P < 0.05) but not in the discrete excellent rate and overlapping rate between the two methods (P > 0.05).
CONCLUSIONS: Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.

BACKGROUND: To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell carcinoma (ESCC) during neoadjuvant chemoradiotherapy (nCRT).
METHODS: The study included 106 ESCC patients treated with nCRT. We collected dosimetric parameters, including vertebral body volumes receiving 10-40 Gy (V10, V20, V30, V40) and EDIC and complete blood counts. Associations of the cell nadir and dosimetric parameters were examined by linear and logistic regression analysis. The receiver operating characteristic (ROC) curves were used to determine the cutoff values for the dosimetric parameters.
RESULTS: During nCRT, the incidence of grade 3-4 lymphopenia, leukopenia, and neutropenia was 76.4%, 37.3%, and 37.3%, respectively. Patients with EDIC ≤ 4.63 Gy plus V10 ≤ 140.3 ml were strongly associated with lower risk of grade 3-4 lymphopenia (OR, 0.050; P < 0.001), and patients with EDIC ≤ 4.53 Gy plus V10 ≤ 100.9 ml were strongly associated with lower risk of grade 3-4 leukopenia (OR, 0.177; P = 0.011), and patients with EDIC ≤ 5.79 Gy were strongly associated with lower risk of grade 3-4 neutropenia (OR, 0.401; P = 0.031). Kaplan-Meier analysis showed that there was a significant difference among all groups for grade 3-4 lymphopenia, leukopenia, and neutropenia (P < 0.05).
CONCLUSIONS: The dose of vertebral bone marrow irradiation and EDIC were significantly correlated with grade 3-4 leukopenia and lymphopenia, and EDIC was significantly correlated with grade 3-4 neutropenia. Reducing vertebral bone marrow irradiation and EDIC effectively reduce the incidence of HT.