新生儿肺部超声在早产儿肺部感染评价中的价值

目的 探讨新生儿肺部超声在早产儿肺部感染评价中的价值。 方法 选取肺部感染早产儿80例为观察组，无肺部感染的早产儿80例为对照组，均给予新生儿肺部超声检查，比较2组肺部超声评分、氧合指数、呼吸指数，比较观察组不同病情、预后患儿肺部超声评分、氧合指数、呼吸指数,分析肺部超声评分和氧合指数、呼吸指数的相关性。 结果 观察组肺部超声评分、氧合指数低于对照组，呼吸指数高于对照组，差异有统计学意义（P＜0.05）。观察组极危重患儿肺部超声评分、氧合指数低于危重和非危重患儿，呼吸指数高于危重和非危重患儿，危重患儿肺部超声评分、氧合指数低于非危重患儿，呼吸指数高于非危重患儿，差异有统计学意义（P＜0.05）。肺部超声评分与呼吸指数呈负相关（r=-0.455，P＜0.05），与氧合指数呈正相关（r=0.470，P＜0.05）。观察组死亡患儿肺部超声评分、氧合指数低于存活患儿，呼吸指数高于存活患儿，差异有统计学意义（P＜0.05）。肺部超声评分预测患儿预后的ROC曲线下面积为0.874，高于呼吸指数和氧合指数（P＜0.05），其截断值为20分时，敏感度和特异度为88.50%和75.00%。 结论 新生儿肺部超声在早产儿肺部感染评价中有较好的效果，值得临床使用。     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)治疗血友病性关节病

目的 观察超声引导下关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（益赛普）治疗血友病性关节病（HA）的价值。方法 回顾性分析32例接受超声引导下穿刺关节腔注射益赛普的HA患者，对比观察治疗前及治疗后1个月血友病关节健康评分（HJHS）、视觉模拟评分（VAS），以及超声所示目标关节增生滑膜厚度、血流信号、Melchiorre及中国早期血友病性关节病超声检测（HEAD-US-C）评分，评估其治疗价值。结果 对32例均成功完成超声引导下穿刺关节腔及腔内注射益赛普，共对18例膝关节、7例肘关节及7例踝关节进行治疗。术后未出现感染、出血等并发症。治疗后1个月，目标关节HJHS、VAS、Melchiorre评分、HEAD-US-C评分及增生滑膜最大厚度、平均厚度、血流信号均低于治疗前（P均<0.01）。结论 超声引导下关节腔内注射益赛普治疗HA安全、有效。     

Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

超声及应变式弹性成像预测超声引导下腘静脉置入血管鞘用于治疗下肢深静脉血栓形成成功与否

目的 分析超声及应变式弹性成像预测超声引导下置入腘静脉血管鞘治疗下肢深静脉血栓形成(DVT)成功与否的价值。方法 回顾性分析103例接受超声引导下置入患侧腘静脉血管鞘的DVT患者的术前超声资料,比较置入血管鞘失败与成功病例腘静脉超声及应变式弹性成像表现差异;绘制差异有统计学意义超声参数的受试者工作特征曲线,获得其预测血管鞘置入失败的阈值,对每个参数阈值赋值1分,得到联合超声评分,以实际置入结果为标准,评价超声单一参数及联合评分的预测效能。结果 103例中,对100例行单侧、3例行双侧腘静脉置入血管鞘,包括左侧腘静脉71支、右侧35支,共106支腘静脉;对其中95支腘静脉置入血管鞘成功(成功组),11支失败(失败组)。相比成功组,失败组腘静脉内径及腘静脉与腘动脉内径比值均较小,血栓为等或高回声,与血管壁边界模糊,腘静脉应变式弹性评分为硬。以超声单一参数及联合评分预测置入血管鞘成功与否的曲线下面积分别为0.909、0.926、0.865、0.899、0.958及0.940(P均＜0.001)。结论 患侧腘静脉超声及应变式弹性成像能有效预测对下肢DVT患者行超声引导下置入腘静脉血管鞘成功与否。