Clinical Phenotype and Genetic Analysis of Twins With Congenital Coagulation Factor V Deficiency.

OBJECTIVE: The aim was to investigate the clinical characteristics and molecular pathogenic mechanism of twins with congenital factor V (FV) deficiency. METHODS: We comprehensively analyzed the clinical manifestations and laboratory test results of a set of twins and their parents and performed point mutation analysis with direct high-throughput exon sequencing. RESULTS: The prothrombin time and activated partial thromboplastin time were prolonged for both probands, and the FV activity levels were 13.0% and 9.8%. Next-generation sequencing showed that the affected individuals harbored a paternal c.5113A>C (p.S1705R) and a maternal c.4949C>T (p.A1650V) heterozygous variants in the FV gene, which conformed to an autosomal recessive inheritance pattern. This is the first report of these point mutations. The older boy also had a congenital patent foramen ovale. CONCLUSION: In this set of twins, missense mutations of the FV gene were related to congenital FV deficiency but unrelated to the patent foramen ovale observed in the older boy.

AbImmPred: An immunogenicity prediction method for therapeutic antibodies using AntiBERTy-based sequence features.

Due to the unnecessary immune responses induced by therapeutic antibodies in clinical applications, immunogenicity is an important factor to be considered in the development of antibody therapeutics. To a certain extent, there is a lag in using wet-lab experiments to test the immunogenicity in the development process of antibody therapeutics. Developing a computational method to predict the immunogenicity at once the antibody sequence is designed, is of great significance for the screening in the early stage and reducing the risk of antibody therapeutics development. In this study, a computational immunogenicity prediction method was proposed on the basis of AntiBERTy-based features of amino sequences in the antibody variable region. The AntiBERTy-based sequence features were first calculated using the AntiBERTy pre-trained model. Principal component analysis (PCA) was then applied to reduce the extracted feature to two dimensions to obtain the final features. AutoGluon was then used to train multiple machine learning models and the best one, the weighted ensemble model, was obtained through 5-fold cross-validation on the collected data. The data contains 199 commercial therapeutic antibodies, of which 177 samples were used for model training and 5-fold cross-validation, and the remaining 22 samples were used as an independent test dataset to evaluate the performance of the constructed model and compare it with other prediction methods. Test results show that the proposed method outperforms the comparison method with 0.7273 accuracy on the independent test dataset, which is 9.09% higher than the comparison method. The corresponding web server is available through the official website of GenScript Co., Ltd., https://www.genscript.com/tools/antibody-immunogenicity.

Investigation and Analysis of Iron-Deficiency Anemia Complicated by Splenomegaly.

OBJECTIVE: This study aimed to determine the incidence of iron-deficiency anemia (IDA) complicated by splenomegaly in our hospital over the past 6 years and to analyze the possible causes of this result. METHODS: This is a retrospective study. In total, 668 patients with IDA who were hospitalized in the hematology department of our hospital from 2013 to 2019 were selected as the research subjects and included in the IDA group, and 3201 patients who underwent outpatient physical examinations in our hospital during the same period were included in the control group. The incidences of splenomegaly in the IDA and control groups were calculated, and the difference was analyzed by means of statistical methods. RESULTS: Among the 668 IDA patients, 46 (6.9%) had splenomegaly, and among the 3201 patients in the control group, 21 had splenomegaly (0.7%). The incidence of splenomegaly was significantly higher in the IDA group than in the control group, and the severity of anemia in the IDA group was associated with the occurrence of splenomegaly. Specifically, the incidence of splenomegaly was 12.4% among patients with severe anemia and as high as 50% among patients with extremely severe anemia. CONCLUSION: IDA is correlated with the incidence of splenomegaly, and the incidence of splenomegaly significantly increases as the severity of IDA increases. This is considered to be caused by extramedullary hematopoiesis.

Regional Injection of CAR-T Cells for the Treatment of Refractory and Recurrent Diffuse Large B Cell Lymphoma: A Case Report.

BACKGROUND: Lymphoma is a common hematological malignancy with many subtypes and considerable heterogeneity. Traditional treatments include chemotherapy, radiotherapy, and surgery. Patients with relapsed, refractory or advanced stage lymphoma have a dismal prognosis. In recent years, chimeric antigen receptors (CARs) have been recognized as powerful tools that redirect antigen-specific T cells independent of human lymphocyte antigen (HLA) restriction and specifically kill tumor cells. Satisfactory results with CAR-based treatments have been achieved in relapsed/refractory B cell leukemia/lymphoma. Our center explored the strategy of subcutaneous injections combined with intravenous drip to overcome certain issues. CASE PRESENTATION: A patient with stage IV refractory and relapsed diffuse large B cell lymphoma was treated with regional and intravenous CAR-T cells. During the observation period, the temperature of the skin at the abdominal wall mass was slightly elevated, and tolerable pain in the injection area was reported. Imaging showed regional liquefactive necrosis. After the sequential administration of ibrutinib and venetoclax, the abdominal wall mass significantly decreased in size. CONCLUSION: The regional injection of CAR-T cells might be safe and feasible for the treatment of regional lesions in patients with refractory and relapsed advanced lymphoma.

[Analysis of Risk Factors Affecting the Chemotherapy-related Infections in Patients with ALL].

OBJECTIVE: To analyze the risk factors affecting the chemotherapy-related infections in patients with acute lympho-blastic leukemia (ALL). METHODS: The clinical data of 102 patients with ALL from January 2014 to December 2018 were collected and retrospectively studies. The risk factors of chemotherapy-related infections were analyzed by univa-riate and multivariate logistic regression. RESULTS: A total of 386 courses of chemotherapy were completed, out of which the infection occurred in 201 course, with the infection rate of 52.07%, identified infection number was 215 case-times, including perianal infection of 13.95% (30/215), oral infection of 13.49% (29/215), blood flow infection of 1721% (37/215), lower respiratory tract infection of 37.21% (80/215), urinary infection of 3.26% (7/215), skin infection of 3.72% (8/215), digestive and intra abdominal infection of 9.30% (20/215), and other infections of 1.86 (4/215). Totally 88 strains of pathogenic bacteria were detected, including 29 Gram-positive bacteria (32.95%), 52 Gram-negative bacteria (59.09%) and 7 fungi (7.95%). Gram-positive bacteria mainly were Staphylococcus haemolyticus and Enterococcus faecium, susceptible to tegacycline, vancomycin and linezolid; Gram-negative bacteria mainly were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, susceptible to tegacycline, amikacin, piperacillin/tazobactam and imipenem; Candida was the dominant fungus. Living in an ordinart ward, neutrophil defi-ciency for more than 7 days after chemotherapy and incomplete remission were independent risk factors of related infections during the induction chemotherapy in ALL inpatients, and hospitalization time also closely related with chemo-therapy-related infections in ALL inpatients (P<0.05). Neutrophil deficiency for more than 7 days after chemotherapy was an independent risk factor of chemotherapy-related infections in ALL inpatients in the consolidation chemotherapy (P<0.05). CONCLUSION: Patients with ALL are prone to chemotherapeutic-related infections, and those who lack neutrophils for more than 7 days after chemotherapy and who do not reach complete remission are more prone to infection. Living in laminar flow ward and reducing hospitalization stay can help reduce the incidence of infection.

Efficacy of Autologous Bone Marrow Mononuclear Cell Transplantation Therapy for Type 2 Diabetes Mellitus: An Updated Meta-Analysis.

INTRODUCTION: Studies of the effects of stem cell therapy on type 2 diabetes mellitus (T2DM) have not reached consistent results. Our meta-analysis aimed to systematically evaluate the efficacy of autologous bone marrow-derived stem cells (ABM-MNCs) on T2DM. METHODS: We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published between 1980 and May 2018. Two researchers screened the literature independently following the inclusion and exclusion criteria. Meta-analysis of the pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated based on either a fixed- or random-effects model. RESULTS: We identified six studies with 206 participants investigating the effects of autologous bone marrow stem cell therapy on T2DM after screening 102 studies found after the initial search. According to the pooled estimates, compared with the control group, after 12-month follow-up the ABM-MNC therapy group had a lower level of HbA1c (MD, - 1.18; 95% CI, - 1.40 to 0.95) and lower required insulin dose (MD, - 2.05; 95% CI, - 3.55 to - 0.55). HbA1c decreased after ABM-MNC therapy compared with before (12 months: MD, - 1.22; 95% CI, - 1.43 to - 1.0). We also observed a significant decrease in insulin requirement after 3-, 6-, 9-, and 12-month follow-up in the ABM-MNC group, respectively. CONCLUSION: Autologous stem cell therapy showed a beneficial effect on T2DM.

Association between interleukin 37 (rs3811047) polymorphism and multiple autoimmune diseases in a Chinese population: A PRISMA-compliant meta-analysis.

OBJECTIVE: Emerging evidence suggests that interleukin 37 (IL-37) plays an important role in the pathogenesis of several autoimmune diseases (ADs), but the correlations are still unclear. We conducted a meta-analysis to explore whether IL-37 gene (rs3811047) polymorphism was associated with susceptibility to multiple ADs in a Chinese population. METHODS: Relevant studies were searched in the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Wangfang databases up to August 31, 2017. Odds ratio (OR) and its 95% confidence interval (95% CI) was used to estimate the strength of the association in different genetic models. The results of fixed or random models were adopted according to the heterogeneity. Publication bias and sensitive analysis were also performed to evaluate the reliability of results. RESULTS: A total of 3161 patients and 4078 controls from 6 studies were included in this meta-analysis. Pooling all data together, a significant association between IL-37 gene (rs3811047 A/G) polymorphism and susceptibility to ADs in the Chinese population was found in all 4 genetic models (allelic model A vs G: OR = 0.73 95% CI = 0.67∼0.79; recessive model AA + AG vs GG: OR = 0.72, 95% CI = 0.65∼0.79; dominant model AA vs AG + GG: OR = 0.59, 95% CI = 0.45∼0.77; homozygous model AA vs GG: OR = 0.55, 95% CI = 0.42∼0.72). No heterogeneity and publication bias was detected in all models. Sensitive analysis indicated that all of the positive results are reliable. CONCLUSION: The IL- 37 (rs3811047) polymorphism contributes to the development of ADs in a Chinese population.