儿童支气管哮喘与注意缺陷多动障碍的关系及其危险因素

近年来儿童慢性疾病与神经精神疾病的关系及其致病机制已成为儿科领域研究的热点和难点。支气管哮喘(简称哮喘)是儿童期常见的慢性疾病之一,最新基于人群的大样本报道证实哮喘与儿童最常见的神经发育障碍性疾病注意缺陷多动障碍(ADHD)之间关系密切。现就哮喘和ADHD的具体关系及其危险因素最新研究进展进行综述,以期认识二者之间的关系及其危险因素,便于哮喘患儿的长程临床管理。     

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

Effect of regular swimming exercise to duration-intensity on neurocognitive function in cerebral infarction rat model

Objective: This study investigated the effect of regular swimming exercise according to the duration-intensity on neurocognitive function in a cerebral infarction rat model.

Methods: Forty male Sprague–Dawley 10-week-old rats, weighing 300 ± 50 g, were subjected to photothrombotic cerebral infarction. The remaining 36 rats were randomly divided into four groups (n = 9 per group: non-exercise (group A); swimming exercise of short duration-intensity (5 min/day, group B); swimming exercise of moderate duration-intensity (10 min/day, group C); and swimming exercise of long duration-intensity (20 min/day, group D). Exercise was performed five times a week for 4 weeks, beginning the day after cerebral infarction. Neurocognitive function was evaluated with the Morris water maze test. Immunohistochemistry and western blot analysis examined brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) at 4 weeks postinfarction.

Results: At 4 weeks postinfarction, escape latency was found to be shorter in group C than in any of groups A, B, or D. Immunohistochemistry revealed the most significant immunoreactivity for BDNF and VEGF in group C. Western blot analysis demonstrated that BDNF and VEGF proteins were markedly expressed in group C.

Conclusions: Regular swimming exercise of moderate duration-intensity may be the most effective exercise protocol for the recovery of neurocognitive function in cerebral infarction rat model.     

Effects of a summer school-readiness programme on measures of literacy and behaviour growth: a pilot study

Young children enter kindergarten with varying levels of readiness and abilities to learn. One factor that contributes to lower levels of school readiness is poverty. One timely, cost-effective, and feasible strategy to boost school readiness, regardless of exposure to high-quality preschool is to leverage the summer months prior to kindergarten entry and provide comprehensive, evidence-based programming immediately before the school year begins. The current study implemented a community-based summer programme targeted at improving school readiness for 25 four- and five-year-old children in a low-income community. Across the 9-week study, children participated in two types of early literacy activities and the Incredible Years social/emotional learning curriculum. Results indicate that participants demonstrated significant growth across three early literacy skills and were rated as overall stable regarding their behaviour across the summer. These results are discussed along with implications and future directions in this line of research.     

以临床胜任力为导向的CBL在急危重症护理本科教学中的实践

目的　探讨临床胜任力为导向的病例教学（case-based learning，CBL）在急危重症护理学本科教学中的可行性和有效性。方法　将急危重症护理本科生120人随机分为CBL教学组和传统教学组。根据每次实习学生人数，CBL教学组分为数个小组，每小组固定一个带教教师，并以小组为单位进行临床教学实践；传统教学组采用既往的临床实习教学方式，即一个学生固定跟随一个带教教师。采用理论考试、技能考试以及问卷调查等多种考核方式评价两组的教学效果，采用SPSS 21.0软件行t检验和卡方检验。结果　与传统教学组相比，CBL教学组在理论考试[（92.5±3.0） vs. （85.3±3.3）]和技能考试[（93.1±4.5） vs. （88.1±3.4）]方面均更好，且差异有统计学意义（P<0.05）；在对教学满意度调查方面，CBL教学组优于传统教学组。结论　以临床胜任力为导向的CBL教学应用于急危重症护理本科教学是可行的，能有效培养学生的临床思维和提高实际的临床胜任力。     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.     

Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.