Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlyi...Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.展开更多
BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnost...BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.展开更多
Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the o...Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the occurrence and recurrence of AF.This review article specifically only focuses on haemoglobin,hematocrit,platelet count,white blood cells(WBCs),lymphocytes,neutrophils,monocytes,neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and red blood cells in the pathophysiology of AF.It emphasizes that there is a higher risk of new-onset AF linked with both low and high haemoglobin levels.A quantitative investigation showed that hematocrit is not linked to the development of AF.The predictive significance of platelet count was reported in nonvalvular AF patients.WBCs are consistent inflammatory markers that are associated with postoperative new-onset AF.Inflammation and in particular,leukocyte activation predisposes to AF.Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.In particular,the peripheral eosinophil and left atrial diameter may be important in mediating inflammation and atrial remodeling in AF.In nonvalvular AF patients,PLR may be an independent risk factor for left atrial appendage thrombogenic milieu.NLR and MLR changes are associated with early recurrence of AF,and NLR change is related to late recurrence of AF after pulmonary vein isolation.Red blood cell distribution width and left atrial dimension were the only independent risk factors associated with AF.展开更多
Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those inv...Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.展开更多
Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of t...Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.展开更多
BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investig...BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.METHODS A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis.Patients were categorized into proximal gastric cancer and distal gastric cancer groups.Laboratory parameters were analyzed.RESULTS Of the 150 patients,84 had proximal gastric cancer and 66 had distal gastric cancer.Dysphagia was significantly more common in the proximal gastric cancer group,while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group(P=0.031).Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality.No significant differences were found in other laboratory or biochemical parameters between the groups.CONCLUSION Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles.The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization,while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality.These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.展开更多
Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their ...Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment.The study aimed to develop degraders with potent efficiency and low toxicity.Methods:Phenotypic profiling,elaborate structure-activity relationships(SAR),rational drug design and degradation profiles investigations,quantitative proteomics analysis and cell-based functional studies,and pharmacokinetic studies were conducted to develop more potent degraders.Results:This study developed novel CRBN-binding moieties throughmethylene deletion in lenalidomide’s isoindole core.Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs.IMiDs,with submicromolar potency.MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3(IKZF1/3)with nanomolar potency via a CRBN-dependent pathway.Mechanistically,MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGDC9 exhibited favorable pharmacokinetic properties in vivo.Furthermore,MGD-C9 exhibited significant synergistic effects with standard-of-care agents in various hematological malignancy cells.Conclusions:These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.展开更多
Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and ...Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.展开更多
Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networ...Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematologic...Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods： This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People＇s Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002（NRS-2002）, Mini Nutritional Assessment（MNA）, Subjective Global Assessment（SGA） and Malnutrition Universal Screening Tools（MUST）, in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results： After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions： Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.展开更多
In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematolo...In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.展开更多
BACKGROUND Patients with hematological diseases are immunosuppressed due to various factors,including the disease itself and treatments,such as chemotherapy and immunotherapy,and are susceptible to infection.Infection...BACKGROUND Patients with hematological diseases are immunosuppressed due to various factors,including the disease itself and treatments,such as chemotherapy and immunotherapy,and are susceptible to infection.Infections in these patients often progress rapidly to sepsis,which is life-threatening.AIM To evaluate the diagnostic efficacy of the neutrophil CD64(nCD64)index,compared to procalcitonin(PCT)and high-sensitivity C-reactive protein(hs-CRP),for the identification of early sepsis in patients with hematological diseases.METHODS This was a prospective analysis of patients with hematological diseases treated at the Fuxing Hospital affiliated with Capital Medical University,between March 2014 and December 2018.The nCD64 index was quantified by flow cytometry and the Leuko64 assay software.The factors which may affect the nCD64 index levels were compared between patients with different infection statuses(local infection,sepsis,and no infection),and the control group and the nCD64 index levels were compared among the groups.The diagnostic efficacy of the nCD64 index,PCT,and hs-CRP for early sepsis was evaluated among patients with hematological diseases.RESULTS A total of 207 patients with hematological diseases(non-infected group,n=50;locally infected group,n=67;sepsis group,n=90)and 26 healthy volunteers were analyzed.According to the absolute neutrophil count(ANC),patients with hematological diseases without infection were divided into the normal ANC,ANC reduced,and ANC deficiency groups.There was no statistically significant difference in the nCD64 index between these three groups(P=0.586).However,there was a difference in the nCD64 index among the non-infected(0.74±0.26),locally infected(1.47±1.10),and sepsis(2.62±1.60)groups(P<0.001).The area under the diagnosis curve of the nCD64 index,evaluated as the difference between the sepsis and locally infected group,0.777,which was higher than for PCT(0.735)and hs-CRP(0.670).The positive and negative likelihood ratios were also better for the nCD64 index than either PCT and hs-CRP.CONCLUSION Our results indicate the usefulness of the nCD64 index as an inflammatory marker of early sepsis in hematological patients.展开更多
BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological in...BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.展开更多
TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastase...TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.展开更多
Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cel...Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.展开更多
Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group....Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.展开更多
As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malig...As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.展开更多
AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 pat...AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA,hepatitis B surface antigen(HBs Ag),and antibodies to HBV core(anti-HBc)and surface antigens.Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction.DNA sequences spanning the S region were analyzed in cases with occult HBV infection.In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.RESULTS HBV DNA was detected in 23(42.6%)of 54 patients with hematological malignancies who were HBsA g negative,but anti-HBc positive,suggesting the presence of occult HBV infection.The complete HBV genome was retrieved from 6 occult HBV patients,and P120 T and S143 L were detected in 3 and 2 cases,respectively.Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143.The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA)with the clone containing T120 mutation,compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot.Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations.120 T mutation impairs the detection of HBsA g by CLEIA.展开更多
Background:Animal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions.Various lineages of mice have been used to investiga...Background:Animal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions.Various lineages of mice have been used to investigate diseases and new therapeutic strategies,and,consequently,hematological and biochemical tests in these laboratory animals are essential to validate scientific studies.Our study seeks to establish reference values for hematological and biochemical parameters of four lineages of mice.Methods:We evaluated the hematological and biochemical profiles of 20 males and 20 females from the lineages Swiss(heterogeneous),BALB/c and C57BL/6(isogenic),and B6D2F1(hybrid),totaling 160 mice.Analysis were standardized using the systems pocH-100iV Diff™for 19 hematological parameters and VITROS®350 for 12 biochemical parameters.Results:Results are shown as means and standard deviation,grouped by lineage and genre.Comparing the values obtained in this study with the values from previous studies,some variations were detected,which could be explained by differences in methodologies or individual variability.Conclusion:Thus our study shows that knowledge and disclosure of the values of physiological parameters of laboratory animals is necessary,and emphasises the importance of considering variations influenced by gender,lineage and genotype in the choice of the best experimental model.展开更多
文摘Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.
基金Supported by Youth Project of Guangxi International Zhuang Medicine Hospital,No.[2022]203Discipline Project of Guangxi International Zhuang Medicine Hospital,No.[2021]33Research Fund of Guangxi International Zhuang Medicine Hospital,No.RCYJ202201.
文摘BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.
文摘Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the occurrence and recurrence of AF.This review article specifically only focuses on haemoglobin,hematocrit,platelet count,white blood cells(WBCs),lymphocytes,neutrophils,monocytes,neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and red blood cells in the pathophysiology of AF.It emphasizes that there is a higher risk of new-onset AF linked with both low and high haemoglobin levels.A quantitative investigation showed that hematocrit is not linked to the development of AF.The predictive significance of platelet count was reported in nonvalvular AF patients.WBCs are consistent inflammatory markers that are associated with postoperative new-onset AF.Inflammation and in particular,leukocyte activation predisposes to AF.Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.In particular,the peripheral eosinophil and left atrial diameter may be important in mediating inflammation and atrial remodeling in AF.In nonvalvular AF patients,PLR may be an independent risk factor for left atrial appendage thrombogenic milieu.NLR and MLR changes are associated with early recurrence of AF,and NLR change is related to late recurrence of AF after pulmonary vein isolation.Red blood cell distribution width and left atrial dimension were the only independent risk factors associated with AF.
文摘Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.
基金supported by grants from the National Natural Science Foundation of China(grant numbers:82370195,82270203,81770211)the Fundamental Research Funds for the Central Univer-sities(grant number:2022CDJYGRH-001)Chongqing Technology Innovation and Application Development Special Key Project(grant number:CSTB2024TIAD-KPX0031).
文摘Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.
基金This study was approved by the Agrı Training and Research Hospital Scientific Research Ethics Committee(No.E-95531838-050.99-86900)conducted in accordance with the Declaration of Helsinki.
文摘BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.METHODS A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis.Patients were categorized into proximal gastric cancer and distal gastric cancer groups.Laboratory parameters were analyzed.RESULTS Of the 150 patients,84 had proximal gastric cancer and 66 had distal gastric cancer.Dysphagia was significantly more common in the proximal gastric cancer group,while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group(P=0.031).Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality.No significant differences were found in other laboratory or biochemical parameters between the groups.CONCLUSION Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles.The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization,while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality.These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.
基金supported by the National Natural Science Foundation of China(No.82404417)Key Project of North China University of Science and Technology(ZD-YG-202408)State Key Laboratory of National Security Specially Needed Medicines Program(No.LTMC2022ZZ006).
文摘Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment.The study aimed to develop degraders with potent efficiency and low toxicity.Methods:Phenotypic profiling,elaborate structure-activity relationships(SAR),rational drug design and degradation profiles investigations,quantitative proteomics analysis and cell-based functional studies,and pharmacokinetic studies were conducted to develop more potent degraders.Results:This study developed novel CRBN-binding moieties throughmethylene deletion in lenalidomide’s isoindole core.Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs.IMiDs,with submicromolar potency.MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3(IKZF1/3)with nanomolar potency via a CRBN-dependent pathway.Mechanistically,MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGDC9 exhibited favorable pharmacokinetic properties in vivo.Furthermore,MGD-C9 exhibited significant synergistic effects with standard-of-care agents in various hematological malignancy cells.Conclusions:These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.
基金supported by a grant of the Deutsche Forschungsgemeinschaft(DFG)to G.B.(#405833349).
文摘Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.
基金the Deanship of Graduate Studies and Scientific Research at Najran University,Saudi Arabia,for their financial support through the Easy Track Research program,grant code(NU/EFP/MRC/13).
文摘Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
文摘Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods： This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People＇s Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002（NRS-2002）, Mini Nutritional Assessment（MNA）, Subjective Global Assessment（SGA） and Malnutrition Universal Screening Tools（MUST）, in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results： After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions： Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.
文摘In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.
基金Supported by Xicheng District Outstanding Talent Project (2018-2019,Shang YX)Beijing Xicheng District Health Commission Young Science and Technology Talent (Science and Technology New Star) Training Project,No.xwkx2020-24
文摘BACKGROUND Patients with hematological diseases are immunosuppressed due to various factors,including the disease itself and treatments,such as chemotherapy and immunotherapy,and are susceptible to infection.Infections in these patients often progress rapidly to sepsis,which is life-threatening.AIM To evaluate the diagnostic efficacy of the neutrophil CD64(nCD64)index,compared to procalcitonin(PCT)and high-sensitivity C-reactive protein(hs-CRP),for the identification of early sepsis in patients with hematological diseases.METHODS This was a prospective analysis of patients with hematological diseases treated at the Fuxing Hospital affiliated with Capital Medical University,between March 2014 and December 2018.The nCD64 index was quantified by flow cytometry and the Leuko64 assay software.The factors which may affect the nCD64 index levels were compared between patients with different infection statuses(local infection,sepsis,and no infection),and the control group and the nCD64 index levels were compared among the groups.The diagnostic efficacy of the nCD64 index,PCT,and hs-CRP for early sepsis was evaluated among patients with hematological diseases.RESULTS A total of 207 patients with hematological diseases(non-infected group,n=50;locally infected group,n=67;sepsis group,n=90)and 26 healthy volunteers were analyzed.According to the absolute neutrophil count(ANC),patients with hematological diseases without infection were divided into the normal ANC,ANC reduced,and ANC deficiency groups.There was no statistically significant difference in the nCD64 index between these three groups(P=0.586).However,there was a difference in the nCD64 index among the non-infected(0.74±0.26),locally infected(1.47±1.10),and sepsis(2.62±1.60)groups(P<0.001).The area under the diagnosis curve of the nCD64 index,evaluated as the difference between the sepsis and locally infected group,0.777,which was higher than for PCT(0.735)and hs-CRP(0.670).The positive and negative likelihood ratios were also better for the nCD64 index than either PCT and hs-CRP.CONCLUSION Our results indicate the usefulness of the nCD64 index as an inflammatory marker of early sepsis in hematological patients.
文摘BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.
基金supported by the National Science Foundation of China (No. 30800402)
文摘TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.
基金supported by Grant National Key R&D Program of China (No.2020YFC2005600 and No.2020YFC2005605)。
文摘Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.
文摘Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.
基金the Key Program of the National Natural Science Foundation(NNSF)of China(No.81230052 and No.81630006).
文摘As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.
基金Supported by Japan Society for the Promotion of Science,No.15H05289
文摘AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA,hepatitis B surface antigen(HBs Ag),and antibodies to HBV core(anti-HBc)and surface antigens.Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction.DNA sequences spanning the S region were analyzed in cases with occult HBV infection.In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.RESULTS HBV DNA was detected in 23(42.6%)of 54 patients with hematological malignancies who were HBsA g negative,but anti-HBc positive,suggesting the presence of occult HBV infection.The complete HBV genome was retrieved from 6 occult HBV patients,and P120 T and S143 L were detected in 3 and 2 cases,respectively.Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143.The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA)with the clone containing T120 mutation,compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot.Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations.120 T mutation impairs the detection of HBsA g by CLEIA.
基金National Council for Scientific and Technological Development(CNPq)Coordination for the Improvement of Higher Level Personnel,Brazil(CAPES)Research Support Foundation for the State of Rio de Janeiro,Brazil(FAPERJ)。
文摘Background:Animal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions.Various lineages of mice have been used to investigate diseases and new therapeutic strategies,and,consequently,hematological and biochemical tests in these laboratory animals are essential to validate scientific studies.Our study seeks to establish reference values for hematological and biochemical parameters of four lineages of mice.Methods:We evaluated the hematological and biochemical profiles of 20 males and 20 females from the lineages Swiss(heterogeneous),BALB/c and C57BL/6(isogenic),and B6D2F1(hybrid),totaling 160 mice.Analysis were standardized using the systems pocH-100iV Diff™for 19 hematological parameters and VITROS®350 for 12 biochemical parameters.Results:Results are shown as means and standard deviation,grouped by lineage and genre.Comparing the values obtained in this study with the values from previous studies,some variations were detected,which could be explained by differences in methodologies or individual variability.Conclusion:Thus our study shows that knowledge and disclosure of the values of physiological parameters of laboratory animals is necessary,and emphasises the importance of considering variations influenced by gender,lineage and genotype in the choice of the best experimental model.
