OBJECTIVE: To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients. RESULTS: Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β₂-microglobulin(β₂-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%（HR=1.253, 95%CI : 0.580-2.889, P =0.018）, age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β₂-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients. CONCLUSION MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans ; Multiple Myeloma/pathology* ; Prognosis ; Plasma Cells/cytology* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Bone Marrow

OBJECTIVE: To investigate the role of MK2 inhibitor MMI-0100 on inflammatory response after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related mechanisms. METHODS: An allo-HSCT mouse model was established. Recipient rats were randomly divided into BMT+NaCl group and BMT+MMI-0100 group, and were injected with NaCl and MMI-0100 every day after transplantation, respectively. Samples of the two groups were collected on d 7 and 14, femur paraffin sections were stained with HE, and pathological changes in the bone marrow cavity were observed under the light microscope. The gene and protein expression levels of pro-inflammatory cytokines IL-1β and IL-18 were detected by qPCR and Western blot. Macrophage typing was detected by flow cytometry. The expression levels of NLRP3 and Caspase-1 were detected by Western blot. RESULTS: Inflammatory cell infiltration in the bone marrow cavity was significantly reduced in the BMT+MMI-0100 group. Western blot results showed that the protein expression levels of IL-1β and IL-18 in the BMT+MMI-0100 group were decreased compared to the BMT+NaCl group on day 7 and day 14 (all P <0.01). The qPCR results showed that compared to the BMT+NaCl group, the IL-18 gene expression levels in the BMT+MMI-0100 group were significantly reduced on day 7 and day 14 (both P <0.01). In the BMT+MMI-0100 group, the expression level of IL-1β gene decreased on day 7 (P <0.05), but increased and was higher than that in the BMT+NaCl group on day 14 (P <0.05). Flow cytometry results showed that the expression of M1 macrophages and M1/M2 ratio decreased in the BMT+MMI-0100 group compared to BMT+NaCl group (all P <0.05). Western blot results showed that the protein expression levels of NLRP3 and Caspase-1 in the BMT+MMI-0100 group were lower than those in the BMT+NaCl group (all P <0.05). CONCLUSION MMI-0100 can ameliorate bone marrow inflammatory injury after allo-HSCT and may act by reducing NLRP3 expression to promote M2 polarization.
Animals ; Interleukin-1beta/metabolism* ; Rats ; Interleukin-18/metabolism* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammation ; Bone Marrow/pathology* ; Protein Serine-Threonine Kinases/metabolism* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Caspase 1/metabolism* ; Macrophages ; Transplantation, Homologous

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( ¹⁸F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL. METHODS: A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and ¹⁸F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of ¹⁸F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described. RESULTS: The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively. CONCLUSION ¹⁸F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Fluorodeoxyglucose F18 ; Bone Marrow/pathology* ; Retrospective Studies ; Positron-Emission Tomography/methods* ; Lymphoma, Large B-Cell, Diffuse/pathology*

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.
Humans ; Animals ; Mice ; Multiple Myeloma/pathology* ; Bone Marrow/pathology* ; Disease Models, Animal ; Drug Resistance ; Tumor Microenvironment

OBJECTIVE: To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis. METHODS: Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m^-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m^-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group. RESULTS: The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001). CONCLUSION Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/diagnostic imaging* ; Bone Marrow/pathology* ; Case-Control Studies ; Bone Marrow Diseases/etiology* ; Osteoporosis/complications* ; Edema/etiology* ; Magnetic Resonance Imaging/methods*

OBJECTIVE: To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis. METHODS: From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m^-2 ranged from 21.39 to 34.46 kg·m^-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs. RESULTS: There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ²=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001). CONCLUSION Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/pathology* ; Bone Marrow/pathology* ; Knee Joint/diagnostic imaging* ; Bone Marrow Diseases/etiology* ; Pain/pathology* ; Arthralgia ; Edema/pathology*

OBJECTIVES: To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS: Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.
Child, Preschool ; Female ; Humans ; Male ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bone Marrow Neoplasms/drug therapy* ; China ; Combined Modality Therapy ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Neuroblastoma/pathology* ; Prognosis ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.
Male ; Adult ; Humans ; Aged ; Lymphoma, Mantle-Cell/drug therapy* ; Prognosis ; Retrospective Studies ; Bone Marrow/pathology* ; Risk Factors

Humans ; Bone Marrow/pathology* ; Hodgkin Disease/pathology* ; Bone Marrow Neoplasms/pathology*

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*