OBJECTIVE:To investigate the effects of nutritional supportive therapy on hematopoietic stem cell transplantation (HSCT) patients and to analyze its relationship with post-transplant hematopoietic reconstitution, acute graft-versus-host disease (aGVHD). METHODS:The clinical data of 76 HSCT patients in our hospital were collected from November 2020 to November 2023, included 46 cases in the nutritional intervention group and 30 in the non-intervention group. After assessing the nutritional status of the intervention group, the five-step therapy principle was followed to implement refined nutritional support treatment, the total daily energy requirement by the patients was calculated based on 25-30 kcal/(kg·d) from the first day of pretreatment to 90 days post-transplantation, followed up until March 2024. The nutritional indices and clinical outcomes of both groups pre-transplant and at 30, 60, and 90 days post-transplant was observed. RESULTS:At 30 days and 60 days after transplantation, the total protein level in the intervention group was higher than before transplantation (P<0.05). At 30 days, 60 days, and 90 days after transplan-tation, the triglyceride levels in both groups were higher than before transplantation (P<0.05). At 30 days and 90 days after transplantation, the HDL-C level in the intervention group was lower than before transplantation (P<0.05). At 60 days after transplantation, the BMI level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30, 60, and 90 days after transplantation, the albumin level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30 days after transplantation, the prealbumin level in the intervention group was higher than that in the non-intervention group (P<0.05). At 30 days and 60 days after transplantation, the total protein level in the intervention group was higher than that in the non-intervention group (P<0.05). At 60 days after transplantation, the low density lipoprotein cholesterol (LDL-C) and triglyceride levels in the intervention group were lower than those in the non-intervention group (P<0.05). At 30 days after transplantation, the HDL-C level in the intervention group was lower than that in the non-intervention group (P<0.05). Time of hematopoietic recons-truction after transplantation: the days for granulocyte reconstitution in the intervention group were earlier than those in the non-intervention group (P<0.05), while there was no statistically significant difference in the number of days for megakaryocyte reconstitution between the two groups (P＞0.05). At 30 days after transplantation, the level of soluble growth stimulus expression gene 2 protein (sST2) in the intervention group was significantly lower than that in the non-intervention group (P<0.05). The level of soluble interleukin-2 receptor (sCD25) in the intervention group at 60 days after transplantation was lower than that at 30 days after transplantation (P<0.05). At different time points after transplantation, there was no statistically significant differences between the two groups in regenerative lslet derived protein 3 alpha (REG3α), soluble tumor necrosis factor receptor 1 (sTNFR1), and elastase inhibitory factor (Elafin) (P＞0.05). CONCLUSION:The implementation of nutritional support therapy not only ameliorates malnutrition and hastens granulopoiesis, but also mitigates the risk of aGVHD and improves the prognosis of patients undergoing hematopoietic stem cell transplantation.
OBJECTIVE:To explore the clinical characteristics and prognosis of second primary cancers (SPC) in patients with hematologic malignancies. Additionally, it aims to characterize hematologic malignancies that develop as SPC following prior solid tumors. METHODS:A retrospective analysis was conducted on the clinical data of patients with hematologic malignancies treated at Wuxi People's Hospital affiliated to Nanjing Medical University from January 2018 to December 2024. Patients with hematological tumors combined with other tumors were screened, and their clinical characteristics and prognosis were evaluated. RESULTS:A total of 236 patients with hematologic malignancies were included in this study. Among them, 116 cases were complicated with SPC, including 26 cases with hematologic malignancies as the first primary cancer(FPC), which were classified as the FPC group of hematological tumors; and 90 cases diagnosed with hematological tumors after suffering from other malignant tumors in the past, which were classified as the SPC group of hematological tumors. The remaining 120 patients had only hematologic malignancies without other cancers (the single hematologic system tumor group). The rate of prior exposure to chemotherapy and/or radiotherapy for the FPC was significantly higher in the hematologic FPC group compared to the solid SPC group (80.8% vs. 34.4%, P < 0.001). Multivariable logistic regression analysis demonstrated that concomitant chronic diseases (OR =1.803, 95%CI :1.035-3.141, P =0.037) and increasing age at diagnosis of hematologic malignancies (OR =1.033, 95%CI :1.009-1.057, P =0.006) were identified as independent risk factors for SPC development. The median OS in the hematologic system tumor with SPC group was lower than that in the single hematologic system tumor group (32 months vs. 49 months), with a statistically significant difference (P < 0.05). Cox proportional hazards model analysis showed that a diagnostic interval of less than 60 months between the two cancers independently predicted inferior overall survival (HR=2.099, 95%CI :1.207-3.650, P =0.009). CONCLUSION:The development of SPC in patients with hematologic malignancies is closely associated with advanced age, chronic comorbidities, and prior exposure to chemotherapy and/or radiotherapy. Patients with both hematologic malignancies and SPC have significantly worse overall survival than those with hematologic malignancies alone. A diagnostic interval of less than 60 months between the two cancers is an independent adverse prognostic factor and may serve as a simple prognostic indicator. Therefore, intensified surveillance and long-term follow-up are warranted for high-risk patients.
OBJECTIVE:To establish a doxorubicin (DOX)-resistant acute myeloid leukemia (AML) cell line and explore the mechanisms of its drug resistance. METHODS:A DOX-resistant THP1 cell line (THP1-Rdox) was established using a low-dose, concentration-gradient intermittent induction method. The resistance effect was evaluated by calculating the resistance index (RI). The expression levels of resistance-related proteins ［P-glycoprotein (P-gp) and lung resistance-related protein (LRP)］ and cell cycle-related proteins (Cyclin A2, Cyclin B1 and Cyclin D1) were examined by Western blot. Intracellular DOX accumulation was observed using confocal laser scanning microscopy. Apoptosis rate and cell cycle distribution were analyzed by flow cytometry. RNA sequencing (RNA-seq) was performed to compare the differential gene expression profiles between DOX-sensitive parental THP1 cells and DOX-resistant THP1-Rdox cells. RESULTS:The DOX-resistant cell line THP1-Rdox was successfully established. The THP1-Rdox cells could stably proliferate at a DOX concentration of 500 ng/ml with a resistance index as high as 198.7. The THP1-Rdox cells exhibited cross-resistance to homoharringtonine (HHT) and paclitaxel (PTX) but no significant resistance to cytarabine (Ara-C). Compared with parental THP1 cells, the expression levels of drug resistance-related proteins P-gp and LRP in THP1-Rdox cells were significantly upregulated. Additionally, THP1-Rdox cells showed decreased uptake and increased efflux of DOX. Notably, after treatment with verapamil (Ver), a specific inhibitor of P-gp, intracellular DOX accumulation was significantly increased in THP1-Rdox cells. Compared with parental THP1 cells, the THP1-Rdox cells exhibited a significantly decreased apoptosis rate, a reduced proportion of cells in the S phase, an increased proportion of cells in the G1 phase, and a marked upregulation in the expression level of the cell cycle regulatory protein Cyclin D1. RNA-seq analysis showed that among the differentially expressed genes between THP1-Rdox and parental THP1 cells, the top 10 most significantly upregulated genes in THP1-Rdox cells were ABCB1, HNRNPA1P9, SEMA3E, MICB, JAML, FGL2, VSIG1, CLEC1B, DLGAP1-AS3, and HOOK1; the top 10 most significantly downregulated genes were MAGEB2, NPTX2, CGREF1, CDO1, GBP5, ZNF595, ZNF630, DTX3, KLHL4 and ZBED6CL. CONCLUSION:Low-dose, concentration-gradient intermittent induction method can successfully establish a DOX-resistant AML cell line, THP1-Rdox. The drug resistance of this cell line is likely attributed to enhanced drug efflux mediated by the elevated expression of P-gp and LRP, as well as cell cycle dysregulation resulting from the upregulation of Cyclin D1 protein.
Objective:To explore the clinical features,treatment strategies,and prognostic factors of patients with new diagnosed Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM),thereby enhancing the diagnostic and therapeutic understanding of this disease.Methods:Comprehensive clinical data were collected from 35 newly diagnosed LPL/WM patients at our hospital between December 2015 and June 2024.A systematic analysis was conducted on baseline characteristics,laboratory parameters,treatment regimens,and follow-up information.Survival analysis was performed using the Kaplan-Meier method,and a Cox regression model was applied to assess prognostic factors.Results:A total of 35 LPL/WM patients were enrolled,with a male predominance(91.4％)and a median age at diagnosis of 69 years(range:32-83).The most common clinical manifestations were fatigue(45.7％),lower limb edema(28.5％),and lymphadenopathy(62.9％).Laboratory findings revealed anemia in 88.6％of patients.The vast majority(94.3％)secreted monoclonal IgM,one patient secreted monoclonal IgG,and one patient had both monoclonal IgM and IgG.The light chain type was predominantly kappa(77.1％).Molecular genetic testing showed a MYD88 L265P mutation rate of 82.4％(28/34),while the CXCR4 mutation rate was lower(17.6％,3/17).The overall response rate was 82.4％in the treatment group containing Bruton's tyrosine kinase inhibitors(BTKi)and 66.7％in the non-BTKi treatment group.With a median follow-up of 70 months,one patient was lost to follow-up and 14 patients died.The median overall survival(OS)for the entire cohort was 71 months.Univariate analysis identifiedβ2-microglobulin ≥4 mg/L at diagnosis was associated with OS(P=0.036)and PFS(P=0.021).Multivariate analysis confirmed β2-microglobulin ≥4 mg/L at diagnosis as an independent adverse prognostic factor for OS(HR=3.854,P=0.025)and PFS(HR=3.201,P=0.030),while receiving BTKi-containing therapy was identified as a protective factor for OS(HR=0.312,P=0.047).Conclusion:This study confirms that elevated β2-microglobulin levels are an independent adverse prognostic factor in patients with LPL/WM.In our center's cohort,patients receiving BTKi therapy achieve higher response rates and longer OS.
OBJECTIVE:To retrospectively analyze the early death of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, build a risk warning model and verify its clinical decision-making benefits. METHODS:The clinical data of 112 NDMM patients treated with daratumumab combination therapy in Tangshan Gongren Hospital from June 2018 to June 2022 were retrospectively collected as the training set, and the clinical data of 78 NDMM patients who received daratumumab combination therapy in the same period were collected as the validation set. According to whether early death occurred during regular follow-up (OS <24 months), the patients were divided into early death group (26 cases) and non-early death group (86 cases). The differences of clinical data between the two groups were analyzed, and Kaplan-Meier survival curves were used to analyze the survival difference of patients with different efficacy. Univariate and multivariate Cox regression analysis were used to analyze the independent risk factors affecting early death of NDMM patients treated with daratumumab. A warning nomogram model for the risk of early death was established, and the predictive performance was analyzed by receiver operating characteristic (ROC) curve and verified internally. RESULTS:According to whether the efficacy of daratumumab treatment achieved partial response (PR), the patients were divided into <PR group (32 cases) and ≥PR group (80 cases). Kaplan-Meier analysis found that the median OS of both groups were not reached, while the OS of patients with efficacy ≥PR was significantly longer than that of patients with efficacy <PR (log-rank χ2=14.225, P <0.001). Multivariate Cox regression analysis showed that older age, R-ISS stage Ⅲ, elevated hs-CRP, and efficacy <PR were independent risk factors for early death in NDMM patients (all P <0.05), and a nomogram model for early death risk in NDMM patients was constructed. ROC analysis and DeLong test showed that the AUC of the nomogram model was 0.894(95%CI : 0.828-0.959), which was higher than that of each individual model, and the differences were statistically significant (all P <0.05). Internal and external validation showed that the nomogram model was stable and had a positive net benefit. CONCLUSION:The OS of NDMM patients who did not reach PR after daratumumab treatment can be affected. Daratumumab treatment early death risk warning model for NDMM has good efficacy, and can be targeted at high-risk population for intensive treatment to improve prognosis.
Acute myeloid leukemia(AML)is a highly heterogeneous disease.This heterogeneity often leads to treatment failure or unsustainable efficacy,and high relapse rates as well as short progression-free survival(PFS)are closely associated with poor prognosis.Cyclin-dependent kinases(CDKs)play a central role in cell cycle regulation,transcription regulation,and metabolic processes,and their aberrant expression or dysfunction is considered as one of the key drivers of AML progression.Recent studies have increasingly focused on CDK inhibitors,aiming to address drug resistance and improve prognosis.Although some CDK inhibitors have shown promising anti-AML potential,challenges such as off-target effects and systemic toxicity remain daunting.This review systematically summarized the research progress of CDK inhibitors in the treatment of AML,with a particular focus on the results of preclinical studies and clinical trials targeting CDKs in AML,such as CDK2,CDK4/6,CDK7,and CDK9.In addition,the limitations of current therapeutic applications of CDK inhibitors were discussed,and potential strategies to overcome these challenges were explored,aiming to provide a reference for optimizing AML treatment regimens.
OBJECTIVE:To analyze the seroepidemiological characteristics and trends of hepatitis B virus (HBV) infection among blood donors in Wuhan from 2016 to 2024, providing data support for monitoring blood safety and evaluating the effectiveness of blood screening. METHODS:A total of 2 026 372 blood samples from Wuhan Blood Center from January 2016 to December 2024 were analyzed. The blood samples were tested using two enzyme-linked immunosorbent assay (ELISA) kits for hepatitis B surface antigen (HBsAg) and one nucleic acid testing (NAT) kit. Samples with reactive results in both HBsAg ELISA tests were defined as HBsAg-positive, while samples with non-reactive HBsAg but reactive HBV NAT results were defined as NAT-positive. HBV prevalence was calculated per 100 000 donations. Demographic characteristics such as age, sex, and marital status, as well as birth cohort and donation frequency were collected, and the characteristics and temporal trends of HBV infection among blood donors were analyzed. The χ2 test was used to assess differences in HBV prevalence across subgroups. Temporal trends in HBV prevalence were analyzed by linear regression. Risk factors associated with HBV infection were identified using logistic regression. RESULTS:From 2016 to 2024, there were 5 237 HBV-positive cases among blood donors in Wuhan, with an overall prevalence of 258.44 per 100 000 donations. This included 3 945 HBsAg-positive cases (prevalence: 194.68 per 100 000 donations) and 1 292 NAT-positive cases (prevalence: 63.76 per 100 000 donations). HBsAg prevalence initially declined (2016-2021), followed by a slight increase (2022-2024), with the rate of 2024 (224.50 per 100 000 donations) being 28.25% lower than that in 2016 (312.90 per 100 000 donations). Univariate analysis showed that male donors (OR=1.490, 95%CI: 1.400-1.586, P<0.001) and married donors (OR=4.060, 95%CI: 3.824-4.311, P<0.001) had a significantly higher risk of HBV infection. The risk of HBV infection increased with age, and the highest risk was observed in donors aged over 45 years (OR=8.138, 95%CI: 7.473-8.862, P<0.001). Donors born after 1992 (OR=0.336, 95%CI: 0.314-0.359, P<0.001), repeat donors (OR=0.094, 95%CI: 0.085-0.103, P<0.001), ethnic minority donors (OR=0.660, 95%CI: 0.565-0.772, P<0.001) and AB blood type donors (OR=0.850, 95%CI: 0.764-0.946, P=0.003) had a significantly lower risk of HBV infection. Age-stratified trend analysis showed a significant decline in HBsAg prevalence in the 18-25 years group (β=-0.930, P<0.001), 26-35 years group (β=-0.885, P=0.001), and 36-45 years group (β=-0.792, P=0.011), but no significant temporal trend was found in the group over 45 years old. The trends of HBV NAT prevalence in all age groups were not significant. HBsAg prevalence declined significantly in unmarried donors and those born after 1992 (β=-0.888, P=0.001； β=-0.896, P=0.001). Except for unmarried donors and male donors, HBV NAT prevalence showed a significant increasing trend across all other demographic subgroups. CONCLUSION:From 2016 to 2024, significant differences in HBV prevalence were observed across various demographic groups among blood donors in Wuhan, though the overall prevalence remained relatively low. This is attributed to the widespread administration of hepatitis B vaccination and the continuous strengthening of blood safety measures. Optimizing the recruitment strategy for blood donors will help further reduce the risk of HBV transmission through blood transfusion.
OBJECTIVE:To investigate the levels of factor Ⅷ (FⅧ) and fibrinogen (FIB) in cryoprecipitate initiating blood (fresh frozen plasma, FFP) and explore the influence of ABO blood type, gender, and age on the levels of FⅧ and FIB in FFP among blood donors in Qingdao. METHODS:A total of 260 bags of cryoprecipitate initiating blood were prepared according to the Technical Operating Procedures for Blood Stations (2019 version). FⅧ and FIB levels were measured, and statistical analyses including t-tests, rank-sum tests, one-way ANOVA with LSD method, and multiple linear regression were performed to analyze the influence of ABO blood type, gender, and age on the levels of FⅧ and FIB. RESULTS:The FⅧ level in cryoprecipitate initiating blood of blood donors in Qingdao was found to be (1.08±0.57) IU/mL. The FⅧ levels in A, B, and AB blood type groups were higher than in O blood type group (P<0.05). Female individuals showed higher FⅧ levels compared to males (P<0.05). Moreover, the FⅧ levels in the 31-40 and 41-58 age groups were significantly higher than that of the 18-30 age group (P<0.05). The FIB level in cryoprecipitate initiating blood was (2.18±0.44) g/L. The FIB levels of female group was higher than that of male group (P<0.05). There were statistically significant differences in FIB levels among different age groups (P<0.05). Multiple linear regression analysis showed that blood group and age were independent factors influencing FⅧ content, age was an independent influence of FIB content. CONCLUSION:ABO blood type was identified as an influencing factor for FⅧ levels in cryoprecipitate initiating blood, with the O blood type having the lowest levels. Age was an influencing factor for both FⅧ and FIB levels, with levels increasing with age. Additionally, females individuals showed higher levels of both FⅧ and FIB compared to males.
OBJECTIVE:To explore the infection characteristics and survival status of lymphoma patients who received intravenous immunoglobulin (IVIG) after autologous hematopoietic stem cell transplantation (AHSCT). METHODS:The clinical data of 121 lymphoma patients who underwent AHSCT from September 2019 to September 2023 were retrospectively analyzed. A Cox proportional hazards model was used to identify risk factors for post-transplant infection-free survival. The patients were divided into IVIG and non-IVIG group according to whether they received IVIG after transplantation, and their infection and survival outcomes were compared. RESULTS:Within 1 year after transplantation, bacterial, viral, and fungal infections occurred in 37 (30.58%), 18 (14.88%), and 3 (2.48%) of the 121 lymphoma patients, respectively. The 1-year overall infection rate after transplantation was 38.1% in the IVIG group (42 patients) and 44.3% in the non-IVIG group (79 patients). In the IVIG group, median infection time was +55 (9-233) days, with 7 cases of early infection, 5 cases of blood stream infection, and 6 cases of respiratory tract infection. In the non-IVIG group, median infection time was +8 (4-122) days, with 27 cases of early infection, 20 cases of bloodstream infection, and 4 cases of respiratory tract infection. IVIG group had fewer early and bloodstream infections, more respiratory tract infections, and a delayed median infection time compared to non-IVIG group. Multivariate Cox regression analysis indicated that pre-transplant serum IgG< 7 g/L, graft MNC< 8.1×108/kg and CD34+ cells≤2.8×106/kg served as independent risk factors for infection-free duration in AHSCT-treated lymphoma patients. The 3-year progression-free survival rates of the IVIG group and non-IVIG group were 52.3% and 48.4%, respectively, and 3-year overall survival rates were 79.4% and 83.0%. At 1 month post-transplant, 69 patients showed a decline in immunoglobulin levels, and 12 patients developed severe hypogamaglobulinemia (HG) (IgG< 4 g/L), with 4 cases (15.4%) in IVIG group and 8 cases (18.6%) in non-IVIG group. One month after transplantation, patients with serum IgG< 4 g/L had a significantly lower survival rate than those with IgG≥4 g/L (55.0% vs. 83.0%). CONCLUSION:In lymphoma patients, post-AHSCT early stage sees mainly bacterial infections. Some develop severe HG. The utilization of IVIG is capable of reducing the incidence of early post-transplant infections and severe HG.
OBJECTIVE:To investigate the differences in plasma transfusion volume among patients with different ABO blood types, and to evaluate the predictive value of relevant clinical indicators such as platelet count (PLT) and other laboratory indicators for the plasma transfusion requirements. METHODS:A single-center retrospective cohort study was conducted including 154 hospitalized patients who received plasma transfusions between January 2022 to December 2023. Patients were grouped by ABO blood group, plasma transfusion volumes and laboratory parameters were compared, and multivariate linear regression was used to identify independent predictors. RESULTS:There was no statistically significant difference in the plasma transfusion volume among patients with different ABO blood types (P>0.05). PLT was significantly negatively correlated with the plasma transfusion volume (r=-0.963, P<0.001), and it was the only statistically significant independent factor in the multiple linear regression analysis.(β=-0.961, P<0.001). CONCLUSION:There is no significant correlation between ABO blood group and plasma transfusion volume. Platelet count is an independent indicator for predicting plasma transfusion volume, providing a new perspective and practical value for precise blood transfusion management.
The development and progression of leukemia are driven not only by intrinsic genetic and epigenetic alterations in leukemia cells,but also by the dynamic remodeling of immune niches within the bone marrow microenvironment(BMM).Accumulating evidence has indicated that leukemic cells can reshape the immune microenvironment through cytokine secretion,metabolic reprogramming,and other mechanisms,inducing T-cell dysfunction/exhaustion,impaired NK-cell effector functions,and immunosuppressive polarization of myeloid cells,thereby establishing a protective niche that facilitates disease progression,drug resistance,and relapse.In parallel,epigenetic mechanisms such as DNA methylation,histone modification,and RNA modifications bridge the phenotypic plasticity of leukemic cells and immune evasion processes by regulating antigen presentation,interferon signaling pathways,chemokine profiles,and immune checkpoint expression,thereby influencing the response to immunotherapy.This review centers on the core conceptual framework of"immune microenvironment remodeling-epigenetic regulation-drug resistance and relapse-combination therapy strategies".It systematically outlines the key immunosuppressive networks and their epigenetic foundations across different leukemia subtypes.Emphasis is placed on the advances and challenges in combining epigenetic drugs,such as demethylating agents and histone deacetylase inhibitors,with immune checkpoint inhibitors,BCL-2 inhibitors,and microenvironment-targeted therapies.Furthermore,it outlines future directions in microenvironment subtyping and precision interventions driven by single-cell and spatial multi-omics technologies,aiming to provide a theoretical basis for optimizing combination treatment strategies in leukemia.
Objective:To analyze the expression level of heterogeneous nuclear ribonucleoprotein U(hnRNP U)and its correlation with prognosis in patients with multiple myeloma(MM),and explore the functional role as well as molecular mechanism of hnRNP U,thereby providing a theoretical basis for development of hnRNP U as a novel therapeutic target for MM.Methods:Based on Gene Expression Omnibus(GEO)database,the expression of hnRNP U in plasma cell diseases and healthy controls was compared.Based on the GSE9782 dataset(n=264),patients were divided into high expression group(n=114)and low expression group(n=150)according to the median expression level of hnRNP U.Overall survival(OS)between the two groups was compared.RPMI 8226,NCI-H929 and MM.1S cell lines were selected as tool cell lines.Following knockdown of hnRNP U by shRNA,the cell proliferation was detected by CCK-8.The apoptosis of MM cells was analyzed by Annexin V/7-AAD staining,and cell cycle was detected by BrdU/DAPI staining followed by flow cytometric analysis.The effect of hnRNP U on the biological characteristics of human MM cells was explored.The effect of knockdown of hnRNP U on DNA damage response pathways was analyzed by Western blot.Results:Analysis of GSE5900 and GSE2113 datasets showed that the mRNA level of hnRNP U rose with the increased degree of malignancy of plasma cell diseases.Survival curve analysis of GSE9782 dataset showed that the high expression group of hnRNP U had a shorter OS than that of the low expression group.Down-regulation of hnRNP U in MM cell lines RPMI 8226,NCI-H929 and MM.1S could inhibit the cell proliferation,promote cell apoptosis and arrest the cell cycle.After knocking down hnRNP U,the expression levels of cleaved PARP and p-H2A.X,as the important markers of activated DNA damage pathway,were significantly increased in MM cells.Conclusion:hnRNP U is highly expressed in several plasma cell diseases including MM,and the high expression of hnRNP U in MM patients predicts poor prognosis.Knocking down hnRNP U can inhibit the malignant progression of MM cells,which is possibly associated with aggravated DNA damage.
Cellular senescence is fundamentally characterized as an irreversible cell cycle arrest state.Studies have revealed that cellular senescence plays a significant role in the pathogenesis and progression of hematological malignancies.Consequently,inducing cellular senescence has emerged as a therapeutic strategy for these malignancies.Traditional Chinese herbal medicine,characterized by its high efficacy and relatively low toxicity,has shown unique potential in inducing senescence in hematological tumor cells.Previous studies have shown that traditional Chinese herbal medicine can induce cellular senescence through mechanisms such as telomere shortening,DNA damage induction,and regulation of the senescence-associated secretory phenotype(SASP)to treat hematological malignancies.This review aims to summarize the recent advances in the mechanisms by which cellular senescence contributes to the pathogenesis of hematological malignancies and the role of traditional Chinese herbal medicine in inducing cellular senescence for therapeutic purposes,thereby providing novel insights and theoretical support for the application of traditional Chinese herbal medicine in the treatment of hematological malignancies.
OBJECTIVE:To analyze the clinical characteristics and prognosis of adult T-cell leukemia/lymphoma (ATLL) patients. METHODS:The clinical data of 32 newly diagnosed ATLL patients admitted to our hospital from January 1, 2014, to October 1, 2021 were retrospectively analyzed. The efficacy and the incidence of complications of different chemotherapy regimens were explored, and the factors that may affect patients' prognosis were analyzed. RESULTS:Among the 32 enrolled ATLL patients, the male-to-female ratio was 1.3:1, and the median age was 53 (range 24-79) years. Of these patients, 21 were of the acute type, 9 of the lymphoma type, and 2 of the chronic type. The main initial manifestations included lymph node enlargement, pulmonary infection, abdominal pain, and rash. Additionally, 28 patients had elevated lactate dehydrogenase (LDH), 14 had hypercalcemia, 20 had bone marrow invasion, and 5 had bone marrow chromosomal abnormalities. 29 patients underwent at least one cycle of chemotherapy, among whom 23 were assessable for efficacy. Of these 23 patients, 9 achieved complete remission (CR) and 4 achieved partial remission (PR), with an objective response rate (ORR) of 56.5%. 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after chemotherapy. By the end of follow-up, 19 cases had died, 11 cases were lost to follow-up, and 2 cases were alive, with a median survival time (MST) of 10.0 (95%CI: 0.0-20.2) months. Multivariate analysis indicated that sex, age, and white blood cell count (WBC) were independent influencing factors for OS in ATLL patients. CONCLUSION:ATLL patients often present with lymph node enlargement, elevated WBC, and elevated LDH at initial diagnosis. Age ≥60 years, and WBC≥10×109/L at initial diagnosis are independent risk factors affecting patient prognosis, while male sex serves as a protective factor for prognosis.
OBJECTIVE:To investigate the clinical characteristics, drug resistance and prognosis of Enterobacteriaceae bloodstream infection (BSI) in children with acute leukemia (AL) following chemotherapy. METHODS:A retrospective analysis was performed on children with Enterobacteriaceae BSI after AL chemotherapy in four hospitals in Fujian Province from January 2015 to December 2023. The clinical characteristics, drug resistance and prognosis of these children were analyzed. RESULTS:A total of 140 children were enrolled, including 117 cases of acute lymphoblastic leukemia and 23 cases of acute myeloid leukemia. BSI occurred in 52.14% of the children during the induction chemotherapy phase, 35.00% during the intensive chemotherapy phase, and 12.86% during the maintenance chemotherapy phase. All children manifested fever, 81.43% had neutropenia, 21.43% had septic shock, 16.43% had no clear infectious lesions, 83.57% had infectious lesions, and 45.71% had two or more multi-site infections. Among the 140 strains of Enterobacteriaceae bacteria, 50.71% were Klebsiella bacteria, 35.00% were Escherichia bacteria, 10.00% were Enterobacter bacteria, and 4.29% were Salmonella bacteria. The highest proportion of multidrug-resistant bacteria (MDRB) and carbapenem-resistant Enterobacteriaceae (CRE) were found in Escherichia (68.89% and 14.89%). Amikacin had the lowest resistance rate among Klebsiella, Escherichia, and Enterobacter. There were no significant differences in pathogen distribution, proportions of MDRB and CRE between the first 4 year group (2015-2018) and the last 5 year group (2019-2023) (P >0.05). There were significant differences in albumin levels, the proportion of anti-infective treatment one week before BSI, proportion of carbapenem anti-infective treatment before BSI, and proportion of deaths between CRE group and non-CRE group (all P <0.05). Among the 140 children, except for 2 children who gave up treatment and the outcomes were unknown, 123 children were cured and 15 children died of BSI. The attributable mortality rate was 10.87% (15/138), and the mortality related to septic shock was 33.33% (10/30). Univariate analysis showed that gender, proportion of septic shock, proportion of CRE strain, albumin level, C-reactive protein (CRP) level and procalcitonin level were significantly different between the cure group and the death group (all P <0.05). Multivariate logistic regression analysis showed that septic shock, lower albumin level and higher CRP level were independent risk factors for death in children with Enterobacteriaceae BSI. CONCLUSION:In children with Enterobacteriaceae BSI following AL chemotherapy, CRE infection is associated with higher mortality. Septic shock, low albumin, and high CRP are independent risk factors for death caused by Enterobacteriaceae BSI.
OBJECTIVE:To summarize the clinicopathological characteristics and survival outcomes of pediatric non-Hodgkin lymphoma (NHL) in Fujian Province. METHODS:Clinical data of 294 newly diagnosed pediatric NHL patients treated at multiple centers in Fujian Province from January 2011 to December 2023 were collected. The characteristics of different pathological subtypes were summarized, Kaplan-Meier survival analysis were performed and Cox proportional hazards regression model was used for prognostic analysis. RESULTS:A total of 294 pediatric NHL patients were included in this study, with a male-to-female ratio of 3.03∶1 and a median age of 7 years (range, 0.9-14 years). The most common subtype was mature B-cell lymphoma, accounting for 59.2% of cases. The majority of patients were diagnosed at stage III/IV (86.2%), with 32 cases (10.9%) involving central nervous system (CNS) infiltration and 89 cases (30.3%) showing bone marrow involvement. The rate of voluntary abandonment significantly decreased after 2018 (abandonment rates before and after 2018: 6/110 (5.45%) vs. 1/184 (0.54%), P =0.012). Furthermore, excluding cases of voluntary abandonment, the 5-year EFS and OS of newly diagnosed pediatric NHL patients from 2018 to 2023 were still significantly higher than those diagnosed from 2011 to 2017 (EFS: 79.3%±3.7% vs. 70.2%±4.5%, P =0.032; OS: 87.7%±2.6% vs. 70.2%±4.5%, P < 0.001). OS improvements after 2018 were significant in patients with BL and LBL (BL: 89.3%±3.6% vs. 73.5%±7.6%, P =0.033; LBL: 89.3%±5.3% vs. 56.5%±10.3%, P =0.001). However, there were no statistically significant differences in EFS or OS for patients with ALCL or DLBCL (all P >0.05). Multivariate survival analysis identified concurrent hemophagocytic lymphohistiocytosis syndrome was an independent risk factors for both EFS and OS in pediatric NHL patients. CONCLUSION:Over the past six years, OS and EFS in children with NHL in Fujian Province have improved markedly, with more pronounced gains in BL and LBL. This trend may be related to the combined effects of reduced voluntary treatment abandonment, more standardized diagnostic and therapeutic pathways, treatment optimization, and updated protocols. HLH at initial diagnosis is an independent risk factor for poor prognosis in pediatric NHL, while remission after two chemotherapy cycles suggests a favorable outcome.
Objective:To analyze a difficult to match blood recipient who tested negative for irregular antibody screening and positive for anti-"Mur"antibodies,and to screen the distribution frequency of Mur blood type antigens and anti-"Mur"antibodies in patients in Guiyang,Guizhou.Methods:Blood type serological tests were used to identify the blood type,screen and identify antibodies,determine antibody titers,and perform cross matching on the blood recipient.Mur blood group antigen and anti-"Mur"antibody were screened by microcolumn gel method.Results:Anti-"Mur"(IgM titer 16,IgG titer 8)was detected in the plasma of the blood recipient.Blood with no agglutination in both the primary and secondary sides was selected.The blood recipient had no adverse reactions after transfusion,indicating effective transfusion.Among patients seeking medical care in the Guiyang area,46 cases(6.62％,46/695)were identified as Mur blood group antigen positive,and 4 cases(0.58％,4/695)were anti-"Mur"antibody positive.Conclusion:Blind matching method can be used to screen for cross matched blood transfusions,but specific antibody identification should be carried in the future.The screening of Mur blood type antigens and anti-"Mur"antibodies has important clinical significance in the Guiyang area.To avoid the missed detection of irregular antibodies,antibody screening cells with positive Mur blood type antigens should be selected for irregular antibody screening.
OBJECTIVE:To evaluate the predictive value of peripheral blood CD4+/CD8+ ratio immediately prior to chimeric antigen receptor T-cell (CAR-T) infusion (Day 0) for treatment efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). METHODS:A retrospective analysis was conducted on data from 49 R/R DLBCL patients who received CAR-T therapy at The First Affiliated Hospital of Soochow University between January 2017 and June 2024. The relationship between the Day 0 peripheral blood CD4+/CD8+ ratio and treatment efficacy was evaluated. RESULTS:At 3 months post-CAR-T infusion, the objective response rate of the 49 patients was 75.5% (37/49), comprising a complete response rate of 55.1% (27/49) and a partial response rate of 20.4% (10/49). Patients with a Day 0 peripheral blood CD4+/CD8+ ratio ≥1 had a significantly higher 90-day response rate than those with a ratio <1 (88.2% vs. 46.7%, P =0.002). Multivariate analysis showed that the Day 0 peripheral blood CD4+/CD8+ ratio was an independent predictor of both progression-free survival (PFS) and overall survival (OS) (P =0.025； P =0.037). Patients with a ratio ≥1 had significantly longer median PFS (11.0 vs. 3.0 months, P =0.011) and median OS (32.1 vs. 8.5 months, P =0.003) compared to those with a ratio <1. CONCLUSION:Peripheral blood CD4+/CD8+ ratio ≥1 immediately prior to CAR-T infusion can predict a higher CAR-T treatment response rate and superior survival outcomes in R/R DLBCL patients.
OBJECTIVE:To explore the risk factors of lower extremity deep vein thrombosis (DVT) in patients with iliac vein compression syndrome (IVCS) and to construct a risk prediction model. METHODS:A total of 187 patients with IVCS admitted to The First Hospital of Lanzhou University from January 2023 to December 2024 were selected as the research subjects. Clinical data such as gender, age, underlying diseases, surgical history, anticoagulation history, body mass index (BMI), and laboratory test results of all patients were collected. According to whether the patients were combined with lower extremity DVT, they were divided into the DVT group (90 cases) and the non-DVT group (97 cases). Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of lower extremity DVT in patients with IVCS. One hundred patients with IVCS admitted to our hospital from January 2025 to July 2025 were selected as the validation group for model validation. The Hosmer-Lemeshow test was used to evaluate the goodness-of-fit of the model, and the predictive performance of the model was evaluated based on the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS:There were statistically significant differences between the DVT group and the non-DVT group in terms of age, BMI, lower extremity mobility disorder, postoperative infection, previous history of thrombosis, D-dimer levels, anticoagulation history, bed rest time, uric acid levels, prothrombin time, and fibrinogen levels (P < 0.05). Multivariate Logistic regression analysis revealed advanced age (OR =1.107, 95%CI : 1.033-1.187, P =0.004), plasma D-dimer >0.5 mg/L (OR =12.799, 95%CI : 1.124-145.782, P =0.040), BMI >25 kg/m2 (OR =5.695, 95%CI : 1.474-22.008, P =0.012), previous history of thrombosis (OR =40.453, 95%CI : 7.234-226.214, P < 0.001), no history of anticoagulation (OR =8.020, 95%CI : 2.274-28.279, P =0.001), bed rest time >72 hours (OR =38.500, 95%CI : 2.696-549.888, P =0.007), hyperuricemia (OR =1.026, 95%CI : 1.016-1.035, P < 0.001) and hyperfibrinogen (OR =3.786, 95%CI : 1.366-10.491, P =0.010) were independent risk factor for lower extremity DVT in patients with IVCS. The Hosmer-Lemeshow test showed that, χ2 =9.608, the P value was 0.294, the goodness-of-fit of the model was good. ROC curve analysis showed that the AUC of the model was 0.946 (95%CI : 0.914-0.978), the specificity was 0.918, and the sensitivity was 0.833. The prediction accuracy of this model was 90.00%, and the Kappa consistency coefficient was 0.780. CONCLUSION:Advanced age, elevated D-dimer, BMI >25 kg/m2, previous history of thrombosis, no anticoagulation prevention, bed rest time >72 hours, hyperuricemia and hyperfibrinogen are all independent risk factors for lower extremity DVT in patients with IVCS. In clinical work, these factors should be emphasized and active intervention measures should be taken to prevent the occurrence of lower extremity DVT, and improve the prognosis of diseases.
OBJECTIVE:By integrating transcriptomics and network pharmacology, we systematically investigated the potential hemostatic mechanism of Bletilla striata (BS). METHODS:Thirty SPF-grade Kunming mice were randomly divided into three groups (n =10 per group): Control group, Model group, and BS group. The BS group was orally administered Bletilla striata extract (2.48 g/kg) for 7 consecutive days, while the Control and Model groups received an equal volume of 0.5% sodium carboxymethyl cellulose (CMC-Na) solution. On day 7, the Model and BS groups were injected via the tail vein with heparin sodium (0.8 U per mouse) to inducesystemic bleeding. The bleeding time (BT) was measured by tail tip amputation, and coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and plasma fibrinogen (FIB) were measured using a semi-automaticcoagulation analyzer. Liver tissues were collected for total RNA extraction and transcriptome sequencing to identify differentially expressed genes (DEGs) related to coagulation pathways. Network pharmacology was used to construct aprotein-protein interaction (PPI) network, screen hub genes, and perform molecular docking to evaluate the binding affinity between the active component militarineand key target proteins. RESULTS:Compared with the Model group, preventive treatment with BS significantly shortened BT and CT (P <0.01), and reversed coagulation parameters: APTT, PT, and TT were significantly reduced (P <0.01), while FIB levels were significantly elevated P <0.001). Transcriptome analysis showed that the hepatic gene expression profile in the BS group was closer to that of the Control group. Network pharmacologyidentified Tnf, Rictor, Nrld1 , and Pnpla2 askey hub genes involved in the hemostaticprocess, all of which exhibited favorable binding affinity with militarine. Compared to the control group, the Model group showed a significant decrease in hepatic Tnf expression but significant increases in Rictor, Nr1d1 , and Pnpla2. After preventive intervention with Bletilla striata , the hepatic Tnf expression in the mice was significantly increased compared to the Model group, while Rictor, Nr1d1 , and Pnpla2 significantly decreased. These findings were further validated by RT-PCR and molecular docking analyses. CONCLUSION:This study reveals that the hemostatic effect of BS is potentially mediated through multi-target synergistic regulation of coagulation factor transcription, coupled with modulations in lipid metabolism and circadian rhythms. It provides a theoretical basis for developing novel hemostatic agents.
