Desired vancomycin trough concentration to achieve an AUC0‐24/MIC ≥400 in Chinese children with complicated infectious diseases

A vancomycin steady‐state trough concentration (C_min) of 15‐20 mg/L is recommended for achieving a ratio of the 24‐hour area under the curve to the minimum inhibitory concentration (AUC_0‐24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between C_min and AUC_0‐24/MIC in paediatric patients. Population‐based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between C_min and the calculated AUC_0‐24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body‐weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, C_min ranges of 5.0‐5.9 and 9.0‐12.9 mg/L were associated with AUC_0‐24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a C_min of 5.0‐5.9 mg/L and AUC_0‐24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved C_min of 9.0‐12.9 mg/L and AUC_0‐24/MIC ≥400 in 2.0‐ and 1.6‐fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin C_min values of 5.0‐12.9 mg/L were strongly predictive of achieving AUC_0‐24/MIC ≥400, and rational dosing regimens of 10‐15 mg/kg q6h were required in paediatric patients, depending on the pathogen.     

Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy

Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.     

AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1

Journal of Neuroimmune Pharmacology - Neuroinflammation is associated with the progression of multiple neurological diseases. Many studies show that SIRT2 involves in multiple inflammatory...     

我院新生儿肠外营养处方的合理性分析

目的：评价我院新生儿肠外营养三种固定组套处方临床实际应用的合理性。方法：收集2018年1-7月我院NICU的新生儿肠外营养处方共320份,患儿共52例,其中早产儿38例,足月儿14例。对新生儿肠外营养三种固定组套处方的成分进行分析,统计患儿的住院时间、使用TPN的时间、患儿摄入的液体量、热卡量、血糖、肝功能等,并结合患儿的生长发育情况,来评价三种固定组套处方的合理性。结果：三种固定组套处方在临床应用中的稳定性能够得到保证,糖速、热氮比、电解质浓度均在合理范围内,但52例患儿中存在3例前期液体量摄入过多,320份处方中存在114份热卡摄入不足,早产儿组套处方中缺少电解质钠和镁,足月儿组套中缺少电解质镁等。结论：我院新生儿肠外营养三种固定组套处方在临床的实际应用中,能够基本满足大多数新生儿的生长发育需求,但肠外营养处方存在热卡和蛋白质摄入不足,需要进一步完善。     

1549例患儿莲必治注射液应用合理性分析及药物利用研究

目的:探讨莲必治注射液在儿童患者中的应用合理性以及中药注射剂在儿童患者中的药物利用研究。方法:对2018年某儿童医院应用莲必治注射液的住院患儿资料进行回顾性分析,结合药品说明书以及患儿年龄、体质量,对给药剂量、给药浓度、用药频次及溶剂选择等方面进行统计分析;计算儿童药物利用指数,初步探讨中药注射剂在儿童患者中的合理评价方法。结果:最终纳入1549例患儿,合理性评分均值为5.43分;适应证合理率最低,仅为45.32%(702/1549);给药浓度均值超过规定范围(0.8~1.5 g/L),最小浓度为0.2 g/L,最大浓度达6.25 g/L。年龄方面,≤1岁患儿的儿童药物利用指数-剂量(cdDUI)>1.1,而>4岁患儿的cdDUI<0.9,不同年龄段患儿的儿童药物利用指数-浓度(ccDUI)均>1,尤以≤6个月为著。体质量方面,≤30 kg患儿的儿童药物利用指数(cDUI)均>1.1,而>30 kg患儿的cDUI均<0.9。结论:从年龄、体质量和平均给药剂量、药物利用指数可见,均存在低年龄或低体重患儿莲必治注射液用药量大,而高年龄或高体质量患儿用药量不足的现象,且均存在给药浓度过高的现象。因此,应加强中药注射剂在儿童中应用的合理性评价。     

Differential diagnosis of coronavirus disease 2019 pneumonia or influenza A pneumonia by clinical characteristics and laboratory findings

BackgroundPneumonia caused by the 2019 novel Coronavirus (COVID‐2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis.MethodsWe retrospectively retrieved data for laboratory‐confirmed patients admitted with COVID‐19–induced or influenza A–induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients'' epidemiological and clinical features, as well as radiologic and laboratory findings.ResultsThe median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID‐19 cohort exhibited higher proportions of fatigue, diarrhea and ground‐glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red‐cell count, hemoglobin and albumin and presented lower levels of monocytes, c‐reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground‐glass opacity, and higher level of albumin were independent risk factors for COVID‐19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia.ConclusionsIn terms of COVID‐19 pneumonia and influenza A pneumonia, fatigue, ground‐glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID‐19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.     

Establishing reference intervals for vitamins A and E in Chinese elderly people using liquid chromatography‐tandem mass spectrometry

BackgroundVitamins A and E play important roles in sustaining life activities and maintaining a good physical condition. However, most people, particularly the elderly, experience micronutrient deficiencies. This study aimed to establish reference intervals (RIs) for vitamins A and E in Chinese elderly people using a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method.MethodsA total of 356 apparently healthy individuals aged ≥64 years who underwent health checkups were randomly selected for the study. Vitamin A and E levels were measured using LC‐MS/MS. The effect of sex on vitamin A and E levels was evaluated, and RIs were established using a parametric method.ResultsFemales showed significantly higher levels of vitamin E than males (p < 0.05). However, no significant sex‐specific difference was observed with vitamin A levels. The RI for vitamin A in the elderly was 0.283–0.730 mg/L. For vitamin E, the RIs were 4.39–15.63, 4.51–16.14, and 4.41–14.67 mg/L for the total, female, and male participants, respectively. In multiple linear regression, alanine aminotransferase, glutamyl transpeptidase, urea, glucose, and uric acid levels increased with increasing vitamin A levels (p < 0.05), and total cholesterol and low‐density lipoprotein cholesterol levels increased with increasing vitamin E levels (p < 0.05). Direct bilirubin levels decreased with increasing vitamin E levels (p < 0.05).ConclusionsThis study established RIs for vitamins A and E in Chinese elderly individuals using an LC‐MS/MS method. We also found that females had significantly higher vitamin E levels than males. The findings could provide a scientific basis for interpreting vitamin status in the elderly.     

超声作用下CTGF-siRNA对大鼠肝纤维化基因治疗的实验研究

目的探讨利用超声微泡造影剂介导携带结缔组织生长因子-小干扰RNA(CTGF-siRNA)真核表达质粒转染大鼠肝细胞的有效性。方法 (1)构建CTGF-siRNA真核表达质粒;(2)将40只实验大鼠随机分为7组:正常组,实验对照组,CTGF-siRNA质粒组,超声联合微泡组,超声联合微泡介导基因低、中、高剂量组;(3)建立肝纤维化模型,基因治疗4周后处死大鼠,超声及病理切片HE染色评价肝纤维化程度,masson染色观察胶原纤维含量,反转录-聚合酶链反应(RT-PCR)检测肝组织中CTGF、Ⅰ型和Ⅲ型胶原的mRNA表达。结果 (1)CTGF-siRNA基因治疗后超声及病理切片显示干预组纤维化程度降低;(2)masson染色显示超声介导微泡基因组胶原纤维含量表达量随着剂量增高而降低(P<0.05);(3)RT-PCR显示超声介导微泡基因组CTGF、Ⅰ型和Ⅲ型胶原的mRNA表达明显低于其他组,且随着质粒剂量增大而减少(P<0.05)。结论超声微泡作用下CTGF-siRNA基因能特异地作用于靶位点,有效抑制肝纤维化进程,提高对肝纤维化干预的特异度。     

SLAM family receptors control pro-survival effectors in germinal center B cells to promote humoral immunity

Expression of the signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) is critical for the germinal center (GC) reaction and T cell–dependent antibody production. However, when SAP is expressed normally, the role of the associated SLAM family receptors (SFRs) in these processes is nebulous. Herein, we established that in the presence of SAP, SFRs suppressed the expansion of the GC reaction but facilitated the generation of antigen-specific B cells and antibodies. SFRs favored the generation of antigen-reactive B cells and antibodies by boosting expression of pro-survival effectors, such as the B cell antigen receptor (BCR) and Bcl-2, in activated GC B cells. The effects of SFRs on the GC reaction and T cell–dependent antibody production necessitated expression of multiple SFRs, both in T cells and in B cells. Hence, while in the presence of SAP, SFRs inhibit the GC reaction, they are critical for the induction of T cell–mediated humoral immunity by enhancing expression of pro-survival effectors in GC B cells.