A novel prognostic scoring model for newly diagnosed FLT3-ITD-positive acute myeloid leukemia

FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML). However, the molecular structure characteristics and widely accepted prognostic factors for FLT3-ITD are still not well described. This study aimed to retrospectively examine 81 patients with FLT3-ITD-positive AML diagnosed and treated at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2018 using the next-generation sequencing 185-gene platform. High variant allele frequency (VAF) [> 0.48, P = 0.0089 for overall survival (OS), P = 0.13 for relapse-free survival (RFS)], multiple ITDs (> 1 ITDs, P = 0.011 for OS, P = 0.033 for RFS) and longer insertion length (> 69 bp, P = 0.14 for OS, P = 0.0078 for RFS) predicted poor survival. The study further proposed an easily applicable scoring model for OS using the Least Absolute Shrinkage and Selector Operation (LASSO) Cox regression model. Also, an independent cohort of 30 patients was used for external model validation. The mode was expressed as follows: 0.659 × FLT3-ITD VAF + 0.375 × FLT3-ITD number + 0.807 × Age + 0.688 × DNMT3A + 1.939 × U2AF1 (FLT3-ITD VAF > 0.48 scored 1; FLT3-ITD number scored 1 if carried 1 ITD, 2 if carried ≥ 2 ITDs; age > 44 years scored 1, the presence of DNMT3A or U2AF1 scored 1; 0 for other conditions). It categorized patients into low-risk (L-R, score < 1, n = 20) and high-risk (H-R, score ≥ 1, n = 61) groups based on the risk score with a significant difference in survival (3-year OS, P < 0.0001; 3-year RFS, P = 0.0005). A prognostic nomogram that integrated these five factors was developed with a concordance index calculation [OS: 0.68, 95% CI (0.64-0.72)].     

外科生物瓣毁损患者使用Venus-A人工瓣膜行经导管主动脉瓣置换术术前CT评估的方法与效果

目的 探讨术前计算机断层扫描(CT)评估外科主动脉生物瓣环内径中多平面曲线瓣环测量法及三维重建法测量间的差异以及基于CT结果指导外科生物瓣毁损患者使用Venus-A瓣膜行经导管主动脉瓣置换术(TAVR)的有效性及安全性.方法 回顾性分析2013年3月至2019年10月连续10例在外科毁损生物瓣中采用Venus-A瓣膜行...     

Antineutrophil cytoplasmic antibody-associated vasculitis with alveolar hemorrhage and ruptured renal aneurysm: A case report and literature review

Rationale:Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing damage to small-vessel vasculitis and mainly occurs in the kidney or lung. We report a rare case of AAV manifesting as alveolar hemorrhage and a renal aneurysm.Patient concerns:A 50-year-old Chinese man presented with repeated coughing, expectoration, fever, hypoxemia, and respiratory failure. The patient suffered from rupture of the renal aneurysm during immunosuppressive therapy.Diagnosis:Considering the clinical picture (fever, progressive hypoxemia, renal insufficiency, hemorrhagic bronchoalveolar lavage fluid, and left retroperitoneal hematoma) along with cANCA-PR3 positivity, and lung biopsy findings, the patient was finally diagnosed with granulomatosis with polyangiitis complicated by alveolar hemorrhage and renal aneurysm.Interventions:The patient was initially treated with immunosuppressive therapy combined with plasma exchange and subsequently with renal arterial embolization due to rupture of the renal aneurysm.Outcomes:The general condition and inflammatory reaction improved with immunosuppressive therapy combined with plasma exchange. Unfortunately, the patient did not respond to treatment and eventually died of respiratory failure and acute kidney injury after the rupture of the renal aneurysm.Lessons:We encountered unprecedented difficulties and challenges with renal aneurysm rupture. The possibility of aneurysmal rupture should be carefully considered and frequently checked for immunosuppressive therapy for AAV.     

新辅助化疗治疗头颈部骨肉瘤单中心临床效果回顾

目的:评价新辅助化疗在头颈部骨肉瘤治疗中的效果.方法:回顾2007-2015年于上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科接受治疗的头颈部骨肉瘤患者的基本信息、围术期治疗信息、影像学信息、病理学信息以及随访记录,采用SPSS 17.0软件包对数据进行统计学分析.结果:最终纳入患者157例,男68例,女89例...     

The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4⁺ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4⁺ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4⁺ T cells when compared with naive, central, and transitional memory CD4⁺ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.     

Tankyrase represses autoinflammation through the attenuation of TLR2 signaling

Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.     

4D-CT特殊重建图像对乳腺癌放疗心脏结构剂量评估影响的研究

目的:通过比较4D-CT图像及特殊重建图像在评估心脏结构"剂量-体积"指标中的差异,探讨不同重建图像对心脏剂量评估的影响。方法:选取15例女性左侧乳腺癌患者行心电门控4D-CT图像扫描,以心动周期5%为间隔重建0～95% 20个时相的图像。将4D-CT图像进行特殊重建,得到最大密度投影(MIP)、最小密度投影(MinI...     

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

PurposeCerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury.Materials and MethodsA mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays.ResultsBhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis.ConclusionMiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.     

敦煌消痹定痛酊对胶原诱导性大鼠关节炎模型NO、cAMP和PGE2影响的实验研究

目的:研究敦煌消痹定痛酊治疗类风湿性关节炎的作用机制,探讨其对胶原诱导性关节炎(CIA)大鼠模型关节液一氧化氮(NO)和3,’5’-环腺苷酸(cAMP)及前列腺素E2(PGE2)含量的影响。方法:建立CIA大鼠模型,用双抗体夹心酶联免疫吸附(ELISA)法检测cAMP和PGE2含量,用亚硝酸盐-比色(Griess)法检测NO含量。结果:敦煌消痹定痛酊能显著降低CIA大鼠关节液中NO和PGE2的含量,升高cAMP的含量。结论:提示敦煌消痹定痛酊对CIA大鼠关节炎具有一定抑制作用,可通过抑制大鼠关节液中NO和PGE2的含量,升高cAMP的含量,从而减轻关节滑膜的炎症,这可能是其治疗类风湿性关节炎的作用机制之一。