The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study.

BACKGROUND: Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA). RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023. RESULTS: The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 109/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment. CONCLUSIONS: p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

Mesenchymal stem cell-derived exosomes overexpressing SRC-3 protect mice from cerebral ischemia by inhibiting ferroptosis.

BACKGROUND: The treatment for cerebral ischemia remains limited, and new therapeutic strategies are urgently needed. Exosome has shown great promise for the treatment of cerebral ischemia. Steroid receptor coactivator-3 (SRC-3) was reported to be involved in neurological performances. In this study, we aimed to investigate the protective effects of mesenchymal stem cell (MSC)-derived exosomes overexpressing SRC-3 on cerebral ischemia in mice. METHODS: The mice were treated with an intracerebroventricular injection of GFP-overexpressed exosomes (GFP-exo) and SRC-3-overexpressed exosomes (SRC3-exo) in a middle cerebral artery occlusion (MCAO) model of cerebral ischemia. RESULTS: The results showed that SRC3-exo treatment significantly inhibited lipid peroxidation and ferroptosis of the neurons subjected to oxygen-glucose deprivation. It further suppressed the activation of microglia and astrocytes, and decreased the production of pro-inflammatory cytokines in the brains of MCAO mice. Furthermore, SRC3-exo treatment reduced the water content of brain tissue and infarct size, which alleviated the neurological damage and improved neurological performances in the MCAO mice. CONCLUSIONS: Our results suggest that MSC-derived exosomes expressing SRC3 can be a therapeutic strategy for cerebral ischemia by inhibiting ferroptosis.

General Design Concept of High-Performance Single-Atom-Site Catalysts for H2 O2 Electrosynthesis.

Hydrogen peroxide (H2 O2 ) as a green oxidizing agent is widely used in various fields. Electrosynthesis of H2 O2 has gradually become a hotspot due to its convenient and environment-friendly features. Single-atom-site catalysts (SASCs) with uniform active sites are the ideal catalysts for the in-depth study of the reaction mechanism and structure-performance relationship. In this review, the outstanding achievements of SASCs in the electrosynthesis of H2 O2 through 2e- oxygen reduction reaction (ORR) and 2e- water oxygen reaction (WOR) in recent years, are summarized. First, the elementary steps of the two pathways and the roles of key intermediates (*OOH and *OH) in the reactions are systematically discussed. Next, the influence of the size effect, electronic structure regulation, the support/interfacial effect, the optimization of coordination microenvironments, and the SASCs-derived catalysts applied in 2e- ORR are systematically analyzed. Besides, the developments of SASCs in 2e- WOR are also overviewed. Finally, the research progress of H2 O2 electrosynthesis on SASCs is concluded, and an outlook on the rational design of SASCs is presented in conjunction with the design strategies and characterization techniques.

Hemophagocytic lymphohistiocytosis secondary to virus infection and followed by lupus nephritis recurrence in a renal transplantation pediatric recipient: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon. CASE PRESENTATION: We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now. CONCLUSIONS: The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

LINC00461 Knockdown Enhances the Effect of Ixazomib in Multiple Myeloma Cells.

BACKGROUND: LINC00461 has been implicated to be involved in several types of cancer while its roles in multiple myeloma remain unclear. Our study aims to investigate the roles of LINC00461 in multiple myeloma and explore its effects on ixazomib therapy. METHODS: LINC00461 and small nuclear ribonucleoprotein polypeptide (SNRP) B2 knockdown stable cell lines were constructed. Cell viability assays including MTT, cell number counting, and colony formation were performed. RNA-pull down and immunoblotting assays were conducted to determine the intramolecular interactions. qRT-PCR and western blotting were conducted to determine the levels of target genes. Kaplan-Meier analysis was used to evaluate overall survival rates. RESULTS: Knockdown of LINC00461 or SNRPB2 enhanced ixazomib's cytotoxicity, as well as affected its regulatory effects on cell apoptosis and cell cycle distribution. Further results showed that LINC00461 knockdown reduced the expression levels of SNRPB2 by their interactions. Additionally, a positive correlation between LINC00461 and SNRPB2 was found in patients with multiple myeloma. Low expression of SNRPB2 was associated with a high survival rate in patients with multiple myeloma. CONCLUSION: Knockdown of LINC00461 enhanced the therapeutic effects of ixazomib against multiple myeloma in part by the regulation of SNRPB2.

The novel HLA-B*48:01:11 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*48:01:11 differs from HLA-B*48:01:01:01 by one nucleotide in exon 4.

Chidamide works synergistically with Dasatinib by inducing cell-cycle arrest and apoptosis in acute myeloid leukemia cells.

This research aimed to explore whether Chidamide works synergistically with Dasatinib in the therapy of Acute myeloid leukemia (AML) and the potential molecular mechanism. The inhibition rate of the Dasatinib and Chidamide combination was significantly better than that of the single-drug application for HL-60 cells. The combination of Dasatinib and Chidamide significantly enhanced the Abnormal histone deacetylase (HDAC) inhibitory activity of Chidamide in Kasumi-1 and HL-60 cells. In the combined group, the proportion of S phase was significantly decreased, and the proportions of G2/M phase were significantly increased. The inhibitory rate of CD34+ CD38- HL-60 cells or Kasumi-1 cells was elevated when the cells were disposed with both Chidamide and Dasatinib. Dasatinib and Chidamide had synergistic antitumor effect. The combination with Dasatinib enhanced the HDAC inhibitory activity of Chidamide, promoted cell apoptosis and cell-cycle arrest of AML cells, and enhanced the inhibition of leukemia stem cell proliferation.

A study of safety acceptance and behavioral interventions for autonomous driving technologies.

Explaining the phenomenon of declining acceptance of automated driving technology (ADT) and predicting trends in acceptance has become an important area of research. To explore the reasons for the decline in acceptance of automated vehicles and how to improve user acceptance, we studied mechanisms of the influence process from the relationship between safety riskiness of ADT and user acceptance, and examined the mediating and moderating effects of the proposed intervention behaviors on the influence relationship between these two. First, an improved acceptance model incorporating safety risk factors was developed. Subsequently, the psychological change process of user acceptance was analyzed based on people's response to accident information. Ultimately, the results show that safety cognition risk regarding ADT has a significant negative impact on user acceptance. Next, the mediating model where user experience was introduced as a moderating variable was designed. From the test results of this model, it is found that the proposed behavioral intervention strategy is effective in attenuating the degree of impact of the safety riskiness of ADT on acceptance. The risk-based acceptance explanation model and intervention method designed in this study provide a scientific basis and practical approach to develop the market for automated vehicles.

Bone marrow-derived mesenchymal stem cells overexpressed with miR-182-5p protects against brain injury in a mouse model of cerebral ischemia.

BACKGROUND: Toll-like receptor 4 (TLR4) plays a critical role in ischemic brain injury by mediating the inflammatory response. The microRNA miR-185-5p suppresses inflammatory signaling by targeting TLR4. This study investigates whether overexpressing miR-182-5p in bone marrow-derived mesenchymal stem cells (BM-MSCs) could potentiate the neuroprotective effects of BM-MSCs in a mouse model of ischemic brain injury. METHODS: We isolated BM-MSCs from mice, transfected the cells with miR-182-5p mimic, determined their MSC lineage through flow cytometry analysis of surface markers, examined miR-182-5p and TLR4 expression levels, and injected them into mice undergone middle cerebral artery occlusion (MCAO). MSC transplanted mice were subjected to behavior assays to determine cognitive and motor functions and biochemical analysis to determine neuroinflammation and TLR4/NF-κB in the ischemic hemisphere. RESULTS: We found that BM-MSCs overexpressing miR-182-5p showed reduced TLR4 expression without affecting their MSC lineage. Mice transplanted with miR-182-5p overexpressing BM-MSCs after MCAO showed significantly improved cognitive and motor functions and reduced neuroinflammation, including suppressed microglial M1 polarization, reduced inflammatory cytokines, and inhibited TLR4/ NF-κB signaling. CONCLUSION: Our findings suggest that overexpressing miR-182-5p in BM-MSCs can enhance the neuroprotective effects of BM-MSCs against ischemic brain injury by suppressing TLR4-mediated inflammatory response.

Proteomic profiling of plasma exosomes from patients with B-cell acute lymphoblastic leukemia.

We aimed to comprehensively investigate the proteomic profile and underlying biological function of exosomal proteins associated with B-cell acute lymphoblastic leukemia. Exosomes were isolated from plasma samples collected from five patients with B-ALL and five healthy individuals, and their protein content was quantitatively analyzed by liquid chromatography with tandem mass spectrometry. A total of 342 differentially expressed proteins were identified in patients with B-ALL. The DEPs were mainly associated with protein metabolic processes and protein activity regulation and were significantly enriched in the Notch and autophagy pathways. Furthermore, we found that ADAM17 and ATG3 were upregulated in patients with B-ALL and enriched in the Notch and autophagy pathways, respectively. Further western blot analysis of exosomes collected from additional 18 patients with B-ALL and 10 healthy controls confirmed that both ADAM17 and ATG3 were overexpressed in exosomes derived from patients with B-ALL (p < 0.001). The areas under the curves of ADAM17 and ATG3 were 0.989 and 0.956, respectively, demonstrating their diagnostic potential. In conclusion, ADAM17 and ATG3 in plasma-derived exosomes may contribute to the progression of B-ALL by regulating the Notch and autophagy pathways. Hence, these proteins may represent valuable diagnostic biomarkers and therapeutic targets for B-ALL.

Mesenchymal Stem Cells Inhibit the Effects of Dexamethasone in Multiple Myeloma Cells.

Mesenchymal stem cells (MSCs) participate in the occurrence and development of multiple myeloma. This study is aimed at exploring whether the presence of MSCs affects dexamethasone's antitumor effects against multiple myeloma. Multiple myeloma cells (OPM-2 and RPMI8226 cells) were cocultured with MSCs with or without dexamethasone. Cell viability was determined by using cell number count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and colony formation assay, respectively. Cell cycle distribution and cell apoptosis were evaluated by using flow cytometry. The mRNA and protein expressions of target genes were checked by using qRT-PCR and western blotting, respectively. It was found that cell viability of multiple myeloma cells increased in the presence of MSCs. Besides, the presence of MSCs suppressed cell apoptosis induced by dexamethasone via the regulation of BCL-2 (B cell lymphoma 2). The presence of MSCs also affected the effects of dexamethasone on cell cycle distribution. Similarly, LINC00461 overexpression suppressed the inhibition of cell proliferation, suppressed the induction of cell apoptosis, and affected the effects on cell cycle distribution induced by dexamethasone insult. However, LINC00461 knockdown enhanced the inhibitory effects on cell proliferation and the induction of cell apoptosis induced by dexamethasone. In summary, MSCs inhibited the effects of dexamethasone on multiple myeloma and its regulatory effects were associated with LINC00461.

SRC3 Promotes the Protective Effects of Bone Marrow Mesenchymal Stem Cell Transplantation on Cerebral Ischemia in a Mouse Model.

Mesenchymal stem cells (MSCs) derived from the bone marrow (BM) are reported to protect against ischemic brain injury. This study aimed to investigate whether the steroid receptor cofactor 3 (SRC3) was involved in MSC-induced neuroprotection. BM-MSCs were isolated from wild-type (WT) and SRC3 knockout (SRC3-/-) mice and transplanted into mice with middle cerebral artery occlusion (MCAO). The MSC identification and differentiation were determined by flow cytometry and Alizarin Red S staining after osteogenic and adipogenic stimulations. The effects of MSCs on brain injury were assessed by brain water content, modified neurological severity score (mNSS), Morris water maze test, and open field test. Finally, the effects of MSCs on MCAO-induced oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) and mRNA levels of SOD1, SOD2, and CAT. We found that SRC3 deficiency did not impact the MSC identification or osteogenic and adipogenic differentiation. MSC-SRC3-/- transplantation in mice that underwent the MCAO procedure exhibited diminished effects on suppression of brain edema, neurological deficits, cognitive disruption, locomotor impairment, and anxiety compared to comparable levels of MSC-WT. Finally, MSC-WT transplantation inhibited MCAO-induced oxidative stress, and the effects were significantly attenuated in MCAO mice transplanted with MSC-SRC3-/-. MSCs suppressed the MCAO-induced upregulation of MDA activity and the inhibition of SOD, GSH, SOD1, SOD2, and CAT levels, and SRC3-deficient MSCs showed significantly reduced effects. Our results indicate that SRC3 plays an important role in mediating the neuroprotective effects of MSCs in mice that experienced ischemic stroke.

An oversampling method for multi-class imbalanced data based on composite weights.

To solve the oversampling problem of multi-class small samples and to improve their classification accuracy, we develop an oversampling method based on classification ranking and weight setting. The designed oversampling algorithm sorts the data within each class of dataset according to the distance from original data to the hyperplane. Furthermore, iterative sampling is performed within the class and inter-class sampling is adopted at the boundaries of adjacent classes according to the sampling weight composed of data density and data sorting. Finally, information assignment is performed on all newly generated sampling data. The training and testing experiments of the algorithm are conducted by using the UCI imbalanced datasets, and the established composite metrics are used to evaluate the performance of the proposed algorithm and other algorithms in comprehensive evaluation method. The results show that the proposed algorithm makes the multi-class imbalanced data balanced in terms of quantity, and the newly generated data maintain the distribution characteristics and information properties of the original samples. Moreover, compared with other algorithms such as SMOTE and SVMOM, the proposed algorithm has reached a higher classification accuracy of about 90%. It is concluded that this algorithm has high practicability and general characteristics for imbalanced multi-class samples.

17ß-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model.

Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood-brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.

SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress.

Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.

Coagulation Factor XIII Subunit A Is a Biomarker for Curative Effects and Prognosis in Malignant Solid Tumors, Especially Non-small Cell Lung Cancer.

BACKGROUND: The expression of coagulant factor XIII subunit A (FXIII-A) is significantly increased in some types of cancer cells and tumor-associated macrophages (TAMs). However, few studies on plasma FXIII-A in cancer patients have been conducted and have shown contradictory results, so the relationship of plasma FXIII-A with the progression and prognosis of malignant tumors is still unknown. This study explored the association of plasma FXIII-A with a curative effect and the prognosis of patients with malignant solid tumors. METHODS: We monitored plasma FXIII-A before and during systemic therapy and assessed its relationship with the curative effect and prognosis of malignant solid tumors, especially non-small cell lung carcinoma (NSCLC), by propensity-adjusted, multivariable logistic regression analysis and survival curve, in a prospective study of 1147 patients with different types of malignant solid tumors. The influencing factors of plasma FXIII-A were also analyzed. RESULTS: We found that D-dimer (D2) = 1 mg/L was the inflection point for the association between FXIII-A and D2: FXIII-A was significantly negatively correlated with D2 (r = -0.39, p < 0.01) and FDP (r = -0.40, p < 0.01) in D2 > 1 mg/L but uncorrelated with D2 or FDP in D2 ≤ 1 mg/L, which provided a method to find a more realistic plasma FXIII-A level. Plasma FXIII-A was positively correlated with age, platelets, lymphocytes, monocytes and carcinoembryonic antigen (CEA). It was found for the first time that plasma FXIII-A was abnormally significantly increased (FXIII-A > 150%) in post-therapy patients, especially in NSCLC and lung metastasis patients, and the incidence of FXIII-A > 150% in lung adenocarcinoma was 16 times higher than that in lung squamous carcinoma. FXIII-A > 150% proved to be an independent risk factor for disease progression in NSCLC patients (OR=5.74, 95% CI: 1.20-27.60, p = 0.029), predicting poor efficacy. The marked decrease in plasma FXIII-A (FXIII-A < 40%) was related to coagulation disorders and poor prognosis with a short survival time (median survival time of 4 months). CONCLUSIONS: Plasma FXIII-A has the potential to be a real-time biomarker with bidirectional indicator effects to assess curative effects and prognosis in malignant solid tumors, especially NSCLC.

A small molecular compound CC1007 induces cross-lineage differentiation by inhibiting HDAC7 expression and HDAC7/MEF2C interaction in BCR-ABL1- pre-B-ALL.

Histone deacetylase 7 (HDAC7), a member of class IIa HDACs, has been described to be an important regulator for B cell development and has a potential role in B cell acute lymphoblastic leukemia (B-ALL). CC1007, a BML-210 analog, is designed to indirectly inhibit class IIa HDACs by binding to myocyte enhancer factor-2 (MEF2) and blocking the recruitment of class IIa HDACs to MEF2-targeted genes to enhance the expression of these targets. In this study, we investigated the anticancer effects of CC1007 in breakpoint cluster region-Abelson 1 fusion gene-negative (BCR-ABL1-) pre-B-ALL cell lines and primary patient-derived BCR-ABL1- pre-B-ALL cells. CC1007 had obvious antileukemic activity toward pre-B-ALL cells in vitro and in vivo; it also significantly prolonged median survival time of pre-B-ALL-bearing mice. Interestingly, low dose of CC1007 could inhibit proliferation of BCR-ABL1- pre-B-ALL cells in a time-dependent manner not accompanied by significant cell apoptosis, but along with cross-lineage differentiation toward monocytic lineage. From a mechanistic angle, we showed that HDAC7 was overexpressed in BCR-ABL1- pre-B-ALL cells compared to normal bone marrow samples, and CC1007 could reduce the binding of HDAC7 at the promoters of monocyte-macrophage-specific genes via inhibition of HDAC7 expression and HDAC7:MEF2C interaction. These data indicated that CC1007 may be a promising agent for the treatment of BCR-ABL1- pre-B-ALL.

Mini-LED, Micro-LED and OLED displays: present status and future perspectives.

Presently, liquid crystal displays (LCDs) and organic light-emitting diode (OLED) displays are two dominant flat panel display technologies. Recently, inorganic mini-LEDs (mLEDs) and micro-LEDs (µLEDs) have emerged by significantly enhancing the dynamic range of LCDs or as sunlight readable emissive displays. "mLED, OLED, or µLED: who wins?" is a heated debatable question. In this review, we conduct a comprehensive analysis on the material properties, device structures, and performance of mLED/µLED/OLED emissive displays and mLED backlit LCDs. We evaluate the power consumption and ambient contrast ratio of each display in depth and systematically compare the motion picture response time, dynamic range, and adaptability to flexible/transparent displays. The pros and cons of mLED, OLED, and µLED displays are analysed, and their future perspectives are discussed.

A Novel Heterozygous Variant in F2 Gene in a Chinese Patient With Coronary Thrombosis and Acute Myocardial Infarction Leads to Antithrombin Resistance.

Thrombophilia refers to a group of conditions where the blood clots more easily than normal. These blood clots can cause problems such as deep vein thrombosis or pulmonary embolism. Most kinds of mutated coagulation factors II (F2) exhibit lower procoagulant activity, but in some cases, a higher coagulation rate has been observed. The underlying mechanism is that those variations can prevent F2s from being inhibited by antithrombin, leading to a contiguous activation of procoagulation, and causing recurrent thromboembolism. In this study, a patient was admitted to our hospital due to repeated chest pain for 2 days and aggravated for 4 h. A medical history investigation showed that he had three deep venous thromboses in the lower limbs and one portal vein thrombosis events during the past 10 years. The electrocardiogram showed Q wave elevation and slight ST segment elevation in lead V2, and coronary angiogram showed a total occlusion of the left anterior descending artery. Laboratory testing found that troponin I was obviously elevated. Family history also indicated that both his father (II-3) and grandfather (I-1) died from pulmonary thromboembolism. Whole-exome sequencing was performed to detect the genetic lesion of the patient, and a novel mutation (c.1621 C>T/p.R541W) of F2 was identified in the patient. This novel mutation resulted in a substitution of arginine by tryptophan, leading to antithrombin resistance (ATR). Our study is consistent with previously published papers. In conclusion, this study not only identifies a novel mutation of F2 and will contribute to the genetic diagnosis and counseling of families with thrombosis but also suggests that the site p.R541 of F2 may play a crucial role in thrombosis.

[Relationship between TET2 Gene SNP rs3733609 C/T and JAK2V617F Allele Burden in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms (MPN). METHODS: The exon 9 of TET2 gene was amplified by RT-PCR, and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing. The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden. The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed. RESULTS: TET2 gene rs3733609 C/T heterozygosity (normal T/T) could be detected in 19 cases of 85 cases of JAK2V617F positive MPN (22.4%) patients, while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers, and the incidence was only 8.5% (9/106). Compared with the negative group (TET2 rs3733609 T/T), there was no significant difference in the median age, hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609 (CT/TC) positive, but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased. In JAK2V617F high allele burden group, TET2 gene SNP rs3733609 was positive in 7 cases (36.8%, 7/19), the ratio was higher than that in the low allele burden group(18.2%, 12/66). CONCLUSION: TET2 SNP rs3733609 C/T may be a new susceptible allelee, which affects the clinical characteristics and clonal evolution of MPN patients.