OBJECTIVE: To construct the inflammation score (IS) and nutrition-immunity score (NIS) for patients with multiple myeloma (MM), and to verify their prognostic stratification effects and significance. METHODS: The clinical data of 129 newly diagnosed MM patients admitted to our hospital from August 2011 to September 2022 were retrospectively analyzed. Univariate and multivariate Cox regression analysis of overall survival (OS) were comducted on clinical parameters, including inflammatory indicators such as red blood cell volume distribution width (RDW) and platelet count (PLT), nutritional-immune indicators such as albumin (ALB), absolute lymphocyte count (ALC), and suppressed immunoglobulin count (S-Ig count). To construct IS and NIS for prognosis, X-tile software and multivariate Cox regression analysis were used to verify the prognostic stratification role and significance of IS and NIS. The time-dependent receiver operating characteristic (ROC) curve, C-index curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical net benefit of IS and NIS in predicting overall survival(OS), and compared to the international staging system (ISS). RESULTS: IS was constructed based on the scores of RDW and PLT, and NIS was constructed based on the scores of ALB, ALC, and S-Ig count. According to X-tile analysis and multivariate Cox regression analysis, IS and NIS can divide the patients into three risk strata respectively: low, medium and high IS and NIS groups. The differences in OS and hazard ratio (HR) between the low, medium, and high strata were statistically significant (P < 0.05). IS and NIS are both independent prognostic predictors for MM. The area under the ROC curve (AUC) and C index of IS and NIS for predicting 1- to 7-year OS were greater than those of ISS, and both were greater than 0.7. The prediction results of IS and NIS for 1-, 3-, and 5-year OS rates were well consistent with the actual observed results. The DCA curves of IS and NIS for predicting 1-, 3-, and 5-year OS were higher than that of ISS in a wide range of threshold probability intervals. CONCLUSION IS and NIS have independent predictive significance for OS in MM patients. Their predictive discrimination, accuracy, and clinical net benefit are higher and better than ISS, and they may have potential application value in MM prognosis.
Humans ; Multiple Myeloma/immunology* ; Prognosis ; Retrospective Studies ; Inflammation ; Male ; Female ; Middle Aged ; ROC Curve ; Aged ; Nutritional Status ; Proportional Hazards Models

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑ^wsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β^{-88 C>G}/β^N). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.
Female ; Humans ; Male ; alpha-Thalassemia/genetics* ; beta-Globins/genetics* ; beta-Thalassemia/diagnosis* ; China ; Cohort Studies ; Genotype ; Molecular Biology ; Mutation

OBJECTIVE: To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients. METHODS: Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM. RESULTS: 36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients. CONCLUSION Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.
Humans ; Multiple Myeloma ; Ferroptosis ; Prognosis ; Hematopoietic System ; Blood Coagulation

Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.
Humans ; Lymphoma, Follicular/drug therapy* ; Duodenal Neoplasms/pathology* ; Prognosis ; Tumor Microenvironment

OBJECTIVE: To screen the differential expression of diffuse large B-cell lymphoma (DLBCL) autophagy-related gene (ARG), explore the mechanism of differential expression of autophagy gene (DEARG) in the occurrence and development of DLBCL and establish a prognostic model. METHODS: Using the NCICCR database containing clinical information and gene expression profile data of 481 patients with DLBCL and the HADb database containing 232 ARGs, the differential expression of ARG in DLBCL was determined by R language, the relationship between ARG and the occurrence and development of DLBCL was analyzed by GO and KEGG, the polygene prognostic model was established by Cox regression algorithm, the survival curve was drawn by Kaplan-Meier method, and the reliability of the prognostic model was evaluated by ROC curve. RESULTS: A total of 122 DEARGs were extracted from lymph node samples of 481 patients with DLBCL and 5 normal lymph nodes, including 4 up-regulated genes and 118 down-regulated genes. GO enrichment mainly focused on ontological annotations such as mitochondrial autophagy, autophagy regulation, and cell response to external stimuli. KEGG enrichment was mainly concentrated in cell senescence, NOD-like receptor signal pathway, PI3K-Akt signal pathway, and PD-1/PD-L1 signal pathway. Survival analysis was performed on 230 samples with complete clinical information. Univariate Cox analysis showed that 20 ARGs were significantly correlated with overall survival of DLBCL patients. Nine prognostic ARGs (HIF1A, CAPN1, ITPR1, PRKCQ, TRAIL, HDAC1, TSC2, NRG3, and MAPK3) were screened by multivariate Cox regression to establish DLBCL ARG prognostic model. Kaplan-Meier survival curve analysis showed that there was significant difference in survival rate between high risk group and low risk group (P<0.001). Multivariate Cox regression analysis showed that international prognostic index and risk value were independent prognostic indicators of DLBCL patients (P<0.05), the area under ROC curve was 0.762 and 0.747, respectively. CONCLUSION DLBCL ARG prognostic model can be used to predict the prognosis of patients, but it still needs to be confirmed by a large sample of clinical studies.
Autophagy ; Biomarkers, Tumor ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Phosphatidylinositol 3-Kinases ; Prognosis ; Reproducibility of Results

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bortezomib/therapeutic use* ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Propensity Score ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

OBJECTIVE: To investigate the serum lipid levels and their prognostic significance in patients with multiple myeloma (MM). METHODS: A total of 87 newly diagnosed MM patients and 87 healthy controls in our hospital from January 2012 to April 2021 were selected. Serum lipid levels were compared between MM patients and healthy controls. The differences of serum lipid levels in patients among two groups of sex, age, hemoglobin (Hb), albumin (ALB), platelet (PLT), β₂-microglobulin (β₂-MG) and bone marrow plasma cell ratio (BMPC), different immune types, different ISS stages, before and after chemotherapy were analyzed. Univariate and COX multivariate regression analysis were used to analyze the influence of clinical parameters such as serum lipid indexes on prognosis of MM. RESULTS: The serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) in MM patients were significantly lower than those in healthy controls (P<0.05). Anemia, low protein and low PLT in patients were related to low cholesterol. The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with low Hb and ALB were significantly lower than those in patients with high Hb and ALB (P<0.05). The Apo B level of low PLT patients was significantly lower than that of high PLT patients (P<0.05). The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with different immune types were significantly different, the above indexes of IgA type were significantly lower than IgG type(P<0.05), IgG type were significantly lower than light chain type(P<0.05), double clone type were significantly lower than light chain type (P<0.05). The levels of TC, LDL-C, and Apo B in patients with different ISS stages were significantly different, stage Ⅱ were lower than those of stage Ⅰ (P>0.05), stage Ⅲ were significantly lower than those of stage Ⅱ and stageⅠ(P<0.05). The levels of TC, TG, LDL-C, HDL-C, Apo A1 and Apo B in patients after chemotherapy were significantly higher than those before chemotherapy (P<0.05). Univariate analysis showed that Hb, PLT, β₂-MG, BMPC, LDL-C and Apo B affected the prognosis of MM. Multivariate analysis showed that BMPC and Apo B were independent factors affecting the prognosis of MM. CONCLUSION The serum cholesterol level is decreased in MM patients, and hypocholesterolemia is related to the classification and staging of the disease. With the improvement of the disease, the serum cholesterol level is increased, and low serum Apo B level predicts a poor prognosis.
Apolipoprotein A-I ; Apolipoproteins B ; Cholesterol, HDL ; Cholesterol, LDL ; Humans ; Immunoglobulin G ; Multiple Myeloma ; Prognosis

OBJECTIVE: In order to conduct high-throughput genome-wide translocation sequencing based on CRISPR/Cas9, Nalm6-cas9 monoclonal cell line expressing Cas9 protein was constructed by lentivirus transduction. METHODS: Lentiviral vectors LentiCas9-Blast, pSPAX2, and pMD2.G were used to co-transfect HEK293T cells to obtain recombinant lentivirus. After Nalm6 cells were infected with the recombinant lentivirus, the cells were screened by Blasticidin, and multiple monoclonal cell lines expressing Cas9 protein were obtained by limited dilution. Western blot was used to detect the expression level of Cas9 protein in monoclonal cell lines, and cell count analysis was used to detect the proliferation activity of monoclonal cell lines. LentiCRISPRV2GFP-Δcas9, LentiCRISPRV2GFP-Δcas9-AF4, LentiCRISPRV2GFP-Δ cas9-MLL plasmids were constructed, and transfected with pSPAX2 and pMD2.G, respectively. T vector cloning was used to detect the function of Cas9 protein in Nalm6-Cas9 monoclonal cell line infected with virus. RESULTS: Western blot showed that Nalm6-Cas9_1-6 monoclonal cell line had high expression of Cas9 protein. Cell count analysis showed that high expression of Cas9 protein in Nalm6-Cas9_1-6 monoclonal cell line did not affect cell proliferation activity. The Nalm6-Cas9_1-6 monoclonal cell line had high cleavage activity, and the editing efficiency of AF4 and MLL genes was more than 90% which was determined by T vector cloning. CONCLUSION Nalm6-Cas9_1-6 monoclonal cell line stably expressing highly active Cas9 protein was obtained, which provided a basis for exploring the translocation of MLL in therapy-related leukemias based on CRISPR/Cas9 genome-wide high-throughput genome-wide translocation sequencing.
CRISPR-Associated Protein 9/genetics* ; CRISPR-Cas Systems ; Genetic Vectors ; HEK293 Cells ; Humans ; Lentivirus/genetics* ; Plasmids

OBJECTIVE: To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment. RESULTS: A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively. CONCLUSION The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide/therapeutic use* ; Doxorubicin/therapeutic use* ; Humans ; Liposomes/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisolone ; Prednisone/therapeutic use* ; Retrospective Studies ; Rituximab/therapeutic use* ; Vincristine/therapeutic use*

OBJECTIVE: To study the expression of B lymphocyte-induced mature protein-1 (BLIMP-1) in regulatory T cells (Tregs) of children with aplastic anemia (AA), and analyze its correlation with the number of Tregs and the levels of inhibitory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β in plasma. METHODS: The peripheral blood samples of 10 newly diagnosed AA children and 10 healthy children were collected for experiment. qPCR was used to detect FOXP3 and PRDM1 mRNA expression levels. Flow cytometry was used to detect the proportion of Tregs, the expression of BLIMP-1 in Tregs, and the levels of cytokines such as IL-2, IL-17A, IL-6, interferon (IFN)-γ, IL-10 and TGF-β in plasma. Pearson correlation model was used to evaluate the relationship between the expression of BLIMP-1 in Treg and the number of Tregs, as well as the levels of IL-10 and TGF-β in plasma. RESULTS: Compared with control group, the proportion of Tregs in peripheral blood of AA children was decreased significantly (P<0.001); The plasma levels of proinflammatory cytokines IL-2, IL-6 and IFN-γ in AA children were increased significantly (P=0.033, P=0.031, P=0.006), and IL-17A also was increased but the difference was not statistically significant (P=0.052), while anti-inflammatory cytokines IL-10 and TGF-β were significantly reduced (P=0.048, P=0.002). The relative expressions level of FOXP3 and PRDM1 mRNA in AA children were significantly lower than those in control group (P=0.037, P=0.016). The expression of BLIMP-1 protein in Tregs of AA children was significantly lower than that in control group (P<0.001). The expression level of BLIMP-1 protein in Tregs was positively correlated with the percentage of Tregs in lymphocytes (r=0.671, P=0.001), and was also positively correlated with the levels of IL-10 and TGF-β in plasma (r=0.500, P=0.029; r=0.486, P=0.030). CONCLUSION The expression of BLIMP-1 in Tregs of AA children is impaired, and the low expression of BLIMP-1 is related to the decrease of the number in Tregs and IL-10 and TGF-β expressions.
Anemia, Aplastic ; Child ; Cytokines ; Flow Cytometry ; Forkhead Transcription Factors ; Humans ; Positive Regulatory Domain I-Binding Factor 1 ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta