[Pharmacokinetics of Recombinant Human Coagulation Factor â § Preparations in Patients with Severe Hemophilia A].

OBJECTIVE: To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients. METHODS: A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated. RESULTS: The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05). CONCLUSION: Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Optimal Rituximab Monotherapy in Splenic Marginal Zone Lymphoma (SMZL): A Case Report and Brief Review.

INTRODUCTION: Splenic marginal zone Lymphoma (SMZL) is a rare, chronic B lymphocyte proliferative disease. Generally, SMZL is accompanied by circulating atypical villous lymphocytes, known as SMZL with villous lymphocytes. Rituximab is a chimeric monoclonal antibody to CD20; recent but limited studies have confirmed its effectiveness in treating SMZL. Given the low incidence and selection of treatment, statistical comparisons of rituximab monotherapy with other available treatment options with the full range of data from previous clinical studies remain sparse. Here, we report a case of SMZL with villous lymphocytes treated by rituximab monotherapy, which is especially infrequently reported. CASE REPORT: A 63-year-old Chinese female was presented to the hospital with complaints of splenomegaly and pain in the spleen area. Immunohistochemistry analysis was positive for IGH, IGK, and IGL clonal rearrangement. Villous lymphocytes were found in peripheral blood and bone marrow, along with further immunotyping results. The case was considered as SMZL with villous lymphocytes. Based on the SMZLSG prognosis assessment, we applied rituximab monotherapy. After eight cycles of rituximab treatment, the patient's condition improved markedly, with blood constituent and size of the spleen returning to normal levels, achieving complete response, with no significant side effect observed. DISCUSSION: The patient provides a typical SMZL with villous lymphocytes case treated with rituximab monotherapy. Currently, the main treatment options include splenectomy and rituximab. After synthesizing a series of current views, we put forward our opinion about the selection of therapy for SMZL patients in order to gain maximum benefits for patients in need of treatment. CONCLUSION: Our analysis found no statistically significant difference between rituximab monotherapy and rituximab combined with chemotherapy, while rituximab treatments resulted in better therapeutic effects than chemotherapy. Rituximab monotherapy has favorable therapeutic effects and minor adverse effects (AEs) in treating SMZL.

Novel insights from spatial transcriptome analysis in solid tumors.

Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics has been widely applied to various tissue types, especially for the study of tumor heterogeneity. In this review, we provide a summary of the research progress in utilizing spatial transcriptomics to investigate tumor heterogeneity and the microenvironment with a focus on solid tumors. We summarize the research breakthroughs in various fields and perspectives due to the application of spatial transcriptomics, including cell clustering and interaction, cellular metabolism, gene expression, immune cell programs and combination with other techniques. As a combination of multiple transcriptomics, single-cell multiomics shows its superiority and validity in single-cell analysis. We also discuss the application prospect of single-cell multiomics, and we believe that with the progress of data integration from various transcriptomics, a multilayered subcellular landscape will be revealed.

Advances in spatial transcriptomics and related data analysis strategies.

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental in biological and medical research, and have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot provide spatial information, while spatial transcriptomics technologies allow gene expression information to be obtained from intact tissue sections in the original physiological context at a spatial resolution. Various biological insights can be generated into tissue architecture and further the elucidation of the interaction between cells and the microenvironment. Thus, we can gain a general understanding of histogenesis processes and disease pathogenesis, etc. Furthermore, in silico methods involving the widely distributed R and Python packages for data analysis play essential roles in deriving indispensable bioinformation and eliminating technological limitations. In this review, we summarize available technologies of spatial transcriptomics, probe into several applications, discuss the computational strategies and raise future perspectives, highlighting the developmental potential.

[Atypical Lymphocytosis:Report of Two Cases and Literature Review].

To improve the diagnosis of atypical lymphocytes and reduce the misdiagnosis rate,we analyzed the medical records of 2 cases with cell morphology suggestive of atypical lymphocytes.One case was diagnosed with infectious mononucleosis and the other with aggressive NK cell leukemia.The purpose of this paper is to emphasize that the diagnosis of atypical lymphocytes based only on morphological interpretation of cells may be incorrect,which should be combined with clinical symptoms,signs,imaging examination,cell immunophenotype,and disease outcome.

[The Value of T Cell subsets and Cytokine Levels Changes in the Clinical Diagnosis, Treatment and Prognosis Evaluation of Multiple Myeloma].

OBJECTIVE: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients. METHODS: The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed. RESULTS: The proportions of NK cells and CD8+T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group (P<0.01), the proportion of CD4+T and the ratio of CD4+/CD8+ were lower than those of the control group (P<0.05); however, there was no significant difference in the numbers CD3+T cells compared with the control group (P>0.05). The proportion of CD4+T and ratios of CD4+/CD8+ in MM patients were lower than those of normal controls, and were negatively correlated with MM staging (r=-0.964, r=-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8+T and NK cells were positively correlated with MM staging (r=0.891, r=0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group (P<0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages (P<0.01). The proportion of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) in MM patients was positively correlated with the concentration of ß2-MG and LDH (r=0.793, r=0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group (P<0.05), which were closely related to MM staging(r=0.839, r=0.917, r=0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM (r=-0.689), and its level gradually decreased with the increase of the disease stage and degree (P<0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group (P<0.05). CONCLUSION: The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.

Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL).

BACKGROUND: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. METHODS: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL. RESULTS: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern. CONCLUSIONS: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease.

[Treatment and Prognosis of Adult T Cell Acute Lymphoblastic Leukemia].

To analyze the treatment and prognosis of T cell acute lymphoblastic leukemia(T-ALL)in adults. Method The clinicobiogical and survival data of 68 adult patients with newly diagnosis T-ALL were retrospectively analzyed. Results The median age of these 68 patients was 23 years(14-60 years).T-ALL was more common in men(81%).After the first cycle of treatment,complete remission was achieved in 50 patients(73%).The highest complete remission(CR) rate was in patients with cortex T-ALL(100%),followed by other T-ALL(73%)and early T-cell precursor lymphoblastic leukemia(54%),(χ 2=5.712,P=0.058).The CR rate for adults aged >35 years was significantly lower than that of patients aged ≤ 35 years(40% vs. 79%,χ 2=6.364,P=0.012).The overall CR rate after the second treatment course was 93%.For patients treated with chemotherapy,autograft hematopoietic stem cell transplantation(auto-SCT),and allogeneic SCT,the median relapse free survival was 10 months,24 months,and not reached,respectively(P=0.002).The 5-year overall survival rate was 25% for all patients;for patients treated with chemotherapy,auto-SCT and allogeneic SCT,the median overall survival was 24 months,34 months,and 30 months,respectively(P=0.007),and the 5-year overall survival rate was 9%,33%,and 38%(P=0.037).Multivariate analysis showed leukocyte count ≥100×10 9/L was a risk factor for decreased relapse free survival(risk ratio 2.540,95%CI=1.058-6.099,P=0.037). Conclusion Adult T-ALL patients have poor prognosis,which may be improved by SCT.

[Expression and role of amyloid precrusor protein gene in acute myeloid leukemia].

OBJECTIVE: To investigate the expression of amyloid precursor protein (APP) gene in acute myeloid leukemia (AML) and its biological behaviour in AML cells. METHODS: The expressions of APP mRNA in 85 AML and 20 nonmalignant hematological diseases patients (as control) were measured by real-time PCR. The expression of APP in AML cell lines was also examined by real-time PCR and Western blot and the results were compared with those in their original subtypes. Small interfering RNAs (siRNAs) targeting APP gene were synthesized and transfected into HL-60 cell by lipofectamine 2000 for 24 h, 48h and 72 h. Cell growth was measured by trypan blue dye exclusion and MTT, differentiation by Wright-Giemsa staining, cell cycle by PI/RNase staining, apoptosis by Annexin V/PI and Hoechst33342 staining. Apoptosis-related protein NF-κB, bcl-2 and Caspase-3 were detected by Western blot after siRNAs transfection for 48 h. Sensitivity to adriamycin was measured by MTT. RESULTS: The expression of APP mRNA among AML subtypes differed significantly (P = 0.019), the highest expression subtype was M(2) with t(8;21) (median 0.1080), followed in order by AML-undefined (0.0467), M(3) (0.0266), M(2a) (0.0221), M(4a) (0.0167), M(5b) (0.0151), and M(4b) (0.0025). APP expression had no significant effect on AML clinical characteristics excepting for subtypes. The expression of APP in Kasumi-1 cells was significantly higher than that of U937 cells (P < 0.05), which was in agreement with APP expression in their original AML subtypes. After siRNAs transfection for 24 h, 48 h, and 72 h, no significant difference in proliferation, differentiation, apoptosis, cell cycle and sensitivity to adriamycin was detected between interfering group and control groups (P > 0.05). CONCLUSIONS: The APP mRNA expression was highest in M(2) with t(8;21) and lowest in M(5b). Down-regulation of APP expression has no significant effects on biological behaviour of HL-60 cells.