Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors

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Pharmacokinetics of levosulpiride after single and multiple intramuscular administrations in healthy Chinese volunteers

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections. Six males and six females received single dose of either 25 mg or 50 mg levosulpiride, or multiple doses of 25 mg every 12 h for 5 consecutive days. In the single 25 mg study, the mean peak plasma concentration (C_max) was 441 ng/mL, the mean area under the concentration–time curve from 0 to 36 h (AUC_0–36) was 1724 ng h/mL, and the mean elimination half-life (t_1/2) was 7.0 h. In the single 50 mg study, the mean C_max was 823 ng/mL, the mean AUC_0–36 was 3748 ng·h/mL, and the mean t_1/2 was 6.8 h. After multiple doses of 25 mg levosulpiride, the average plasma concentration (C_av) was 136 ng/mL, the fluctuation index (DF) was 3.60, and the accumulation ratio (R) was 1.2. Levosulpiride injections appeared to be well tolerated by the subjects, and can be used for successive administration.KEY WORDS: Levosulpiride, Pharmacokinetics, Intramuscular administration, Safety and tolerability     

BCG-induced trained immunity in macrophage: reprograming of glucose metabolism

Abstract

Memory is no longer a privilege of adaptive immunity. Innate immune cells can exhibit a long-term immune activation after infection or vaccination, which is called “trained immunity.” In addition to defense against mycobacterial infection, BCG-induced trained immunity can also exert nonspecific protection, which is regulated by metabolic rewiring and epigenetic reprograming. Enhanced glycolysis and glutamine-driven tricarboxylic acid cycle have been proven to be important metabolic pathways for trained immunity induced by BCG, which is dependent on Akt/mTOR pathway.     

Exploring the genetic pathogenicity of aortic dissection from 72 Han Chinese individuals using next-generation sequencing

Aortic dissection (AD) is a heterogeneous genetic disease with high morbidity and mortality. Although many genes predispose patients to AD, the pathogenic spectrum remains incomplete. This study aims to (a) investigate whether genotype differences exist between Stanford A and B AD individuals, and (b) broaden the pathogenic genetic spectrum of AD and reported novel variants of AD-associated genes. The DNA of 72 unrelated Han Chinese individuals with AD was tested by whole-exome sequencing. Of 142 AD-associated genes, 10 pathogenic variants, and 48 likely pathogenic variants in 36 genes were identified among 39 cases. The diagnostic yield was 54.2%. Of the 58 positive variants, 27 were novel. FBN1 was the most frequently positive gene in both Stanford A and Stanford B. Twenty-seven positive variants from 18 COL family genes were distributed in 36.8% of Stanford A and 6.7% of Stanford B cases. We emphasize that positive variants of COL family genes show distribution predominance and strong pathogenicity in Stanford A, while positive variants of smooth muscle cell pathway genes present distribution advantages mainly in Stanford B cases. Our findings provide a new perspective for both the pathogenic mechanism and the treatment of AD.     

Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation

Inflammation Research - Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3)...     

(1,3)-β-D葡聚糖、半乳甘露聚糖联合降钙素原检测对侵袭性真菌感染的诊断价值

目的 探讨血清中(1,3)-β-D葡聚糖[ (1,3) β-D-glucan,G]和半乳甘露聚糖(galactomannan,GM)联合降钙素原(procalcitonin,PCT)检测对患者侵袭性真菌感染(invasive fungal infections,IFI)的临床诊断价值。方法 选取徐州市中心医院2017年1月至2018年6月收治的具有高危IFI因素的住院患者447例,根据血培养结果分成实验室诊断组和非实验室诊断组。分别采用定量检测、比色法及电化学发光法对血清中G、GM和PCT的含量进行检测,评价三者联合检测对IFI的早期诊断价值。结果 447例患者中实验室诊断组51例,非实验室诊断组396例。51例患者中G试验阳性39例,GM试验阳性14例,PCT阳性41例。G试验、GM试验、PCT检测的敏感性为76.47%、27.45%和80.39%;特异性为76.77%、87.12%和66.67%;阳性预测值为29.77%、21.54%和23.70%;阴性预测值为96.20%、90.31%和96.35%;阳性似然比为3.29、2.13和2.41;阴性似然比为0.31、0.83和0.29;Youden指数为0.53、0.15、0.47。三者联合检测的敏感性为94.12%、特异性为62.88%、阳性预测值为24.62%,阴性预测值为98.81%,阳性似然比为2.54,阴性似然比为0.09,Youden指数为0.57。三者联合检测的敏感性均高于G试验、GM试验、PCT单独检测及G/GM联合试验,差异具有统计学意义(χ2值分别为6.331、47.545、4.320和5.299,P值均<0.05)。三者联合检测的特异性均低于G试验、GM试验单独检测及G/GM联合试验,差异具有统计学意义(χ2值分别为18.127、62.061和16.754,P值均<0.05),但与PCT单独检测相比差异无统计学意义(χ2=1.245,P>0.05)。结论 G、GM以及PCT三者联合检测可显著提高IFI检出的敏感性,并且对IFI的诊断排除有很大的价值,从而降低假阳性率和假阴性率,为IFI的早期诊断提供一定的依据。     

Chronic endometritis and reproductive failure: Role of syndecan‐1

Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan‐1 has been identified as a biomarker of plasmacyte, and syndecan‐1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan‐1, the progress of syndecan‐1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.