The FLT3 Y842D mutation may be highly sensitive to midostaurin: a case report

A Y842D mutation within the activation loop of fms-like tyrosine kinase 3 (FLT3) has been shown to confer strong resistance to sorafenib in vitro. Whether this type of mutation exerts clinically significant effects in patients with acute myeloid leukaemia (AML) remains unclear. Here, a novel Y842D activating mutation within the kinase domain of FLT3, in a pregnant patient with de novo hyperleucocyte acute myeloid leukaemia, is described. Following induction failure with standard dose idarubicin and cytarabine (IA), the patient received re-induction combined with midostaurin, a promising agent targeting mutant-FLT3, and IA regimen. Fortunately, morphological remission was achieved. During the period of midostaurin treatment, the patient exhibited a symptom that was characteristic of differentiation syndrome, which disappeared following treatment with methylprednisolone. The present case revealed that Y842D, an uncommon activating mutation in the activation loop of FLT3, may be a midostaurin-sensitive mutation type in patients with acute myeloid leukaemia.     

Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population: a cross-sectional study

BACKGROUNDEpidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.METHODSIn this cross-sectional study, adults aged 35–75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min).RESULTSAmong 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08–1.13), 1.36 (1.33–1.39), 1.68 (1.64–1.72), 2.01 (1.96–2.07) and 2.58 (2.50–2.67), respectively (P_trend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors. CONCLUSIONSThere was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Over the past several years, the rapid development of smart wrist-worn devices has resulted in a convenient approach to monitoring resting heart rate (RHR) in daily life. RHR is becoming a promising indicator of cardiovascular health. Observational studies have shown that elevated RHR is associated with increased all-cause and cardiovascular mortality in populations with or without cardiovascular disease (CVD).^[1,2] Elevated RHR has also been found to be associated with cardiovascular risk factors (CVRFs), such as hypertension, diabetes mellitus, dyslipidemia, low physical activity and smoking, indicating its potential to reflect total cardiac risk.^[3–7] There is abundant epidemiologic evidence supporting the association between a single CVRF and RHR, but studies exploring associations between multiple CVRFs and RHR are limited. CVRFs tend to cluster within individuals, and several weak risk factors combined may result in a much higher risk than that due to a single strong risk factor. According to a cross-sectional survey in China, more than 45% of Chinese adults have two or more coexisting CVRFs.^[8] Thus, it is important to consider the situation of multiple CVRFs clustering. However, very few studies have analyzed the association between CVRFs clustering and RHR, and several aspects remain unknown. Firstly, prior studies mainly focused on the relation between metabolic risk factors and RHR.^[9–11] Behavioral risk factors such as smoking, physical activity and alcohol use have rarely been considered, even though these risk factors also have a significant effect on heart rate.^[3,5,7] Secondly, most studies merely dealt with the relation of CVRFs clustering number with RHR, while regarding each number of risk factors, different combinations of risk factors have not yet been considered before.^[9,12] It is important to consider different CVRF clustering patterns since some risk factors combined may lead to a higher risk of elevated RHR than others, even if the number of CVRFs is the same. Thirdly, prior studies did not assess associations stratified by sex and age. It has been well documented that RHR levels differ by sex and age. The RHR in women was on average 2–7 beats/min higher than that in men, and there was a decrease in the RHR with age.^[13,14] As such, whether the associations of CVRFs clustering with RHR varied between sex and age remains unclear. Taking advantage of the large sample size in our study, we are able to include a wider range of CVRFs (metabolic and behavioral risk factors), comprehensively evaluate the association between these CVRFs clustering and RHR, and further explore sex and age differences. This finding may inform us whether RHR can be used as a simple and efficient metric for the identification of high-risk individuals who require more intensive risk factor evaluation and earlier cardiovascular health monitoring in resource-constrained countries with substantial CVD burdens, such as China. To bridge this knowledge gap, we used data from the China PEACE Million Persons Projects, a nationwide screening project, to explore (1) the association between the number of CVRFs clustering and elevated RHR in the overall population and populations stratified by age and sex; and (2) the associations between different CVRFs clusters and the risk of elevated RHR in the overall population and populations stratified by sex.     

Point-of-Care Tests for Rapid Detection of Porcine Epidemic Diarrhea Virus: A Systematic Review and Meta-Analysis

The timely and accurate diagnosis of porcine epidemic diarrhea virus (PEDV) infection is crucial to reduce the risk of viral transmission. Therefore, the objective of this review was to evaluate the overall diagnostic accuracy of rapid point-of-care tests (POCTs) for PEDV. Studies published before 7 January 2022 were identified by searching PubMed, EMBASE, Springer Link, and Web of Science databases, using subject headings or keywords related to point of care and rapid test diagnostic for PEDV and PED. Two investigators independently extracted data, rated risk of bias, and assessed the quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model were used for performing the meta-analysis. Threshold effect, subgroup analysis, and meta-regression were applied to explore heterogeneity. Of the 2908 records identified, 24 eligible studies involving 3264 specimens were enrolled in the meta-analysis, including 11 studies on evaluation of lateral flow immunochromatography assay (ICA)-based, and 13 on nucleic acid isothermal amplification (NAIA)-based POCTs. The overall pooled sensitivity, specificity and diagnostic odds ratio (DOR) were 0.95 (95% CI: 0.92–0.97), 0.96 (95% CI 0.88–0.99) and 480 (95% CI 111–2074), respectively; for ICA-based POCTs and the corresponding values for NAIA-based, POCTs were 0.97 (95% CI 0.94–0.99), 0.98 (95% CI 0.91–0.99) and 1517 (95% CI 290–7943), respectively. The two tests showed highly comparable and satisfactory diagnostic performance in clinical utility. These results support current recommendations for the use of rapid POC tests when PEDV is suspected.     

Structure-activity relationships of phencyclidine derivatives in rat cerebellum

The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.     

中国人2型糖尿病合并高甘油三酯血症患者脂蛋白酯酶基因突变及功能分析

目的 研究中国人2型糖尿病合并高甘油三酯血症患者脂蛋白醒酶(1ipoprotein lipase,LPL)基因突变及对酶功能的影响,从脂代谢途径探讨引发糖尿病的遗传因素。方法 对高甘油三酯及血脂正常的2型糖尿病患者和正常人的LPL基因进行研究。利用PCR—SSCP、PCR—RFLP及DNA测序技术对LPL基因的启动子和10个外显子区域进行突变检测,针对特异位点进行体外定点突变和酶活力表达研究,利用网上工具平台Swiss-PDB Viewer对正常和突变蛋白进行二级结构模拟分析。结果 在177例高甘油三酯2型糖尿病患者中检测到4种错义突变：Ala71Thr、Val181IIe、Glyl88Glu和Glu242Lys,在正常血脂的糖尿病患者和健康人组中没有检出以上突变。这4种突变位于进化上高度保守的氨基酸位点,并分别在高度保守的外显子3、5及6区域。体内和体外酶活力研究表明,这4个突变均引起了酶活力降低甚至失活,其改变程度可以从它们所在序列的保守性、在酶功能结构城中的相对位置、相应的二级结构改变和氨基酸特性获得解释。结论 在受累个体中,LPL突变是引起患者血浆甘油三酯升高的直接原因,是其发展成2型糖尿病的遗传性易感因素。     

Halogen-free instinct flame-retardant waterborne polyurethanes: composition,performance, and application

Ideal halogen-free instinct flame-retardant waterborne polyurethanes have high flame-retardant efficiency, environmental friendliness, fine compatibility, and good thermostability. Phosphorus flame-retardants are currently widely used in halogen-free instinct flame-retardant waterborne polyurethanes (HIFWPU), especially those with phosphorous–nitrogen co-structures. Phosphorous–nitrogen HIFWPU have become a hotspot because their co-structures provide higher flame-retardance as compared to waterborne polyurethanes. This review introduces three main types of HIFWPU based on composition, performance and application. HIFWPU not only have improved flame-retardance but also satisfy the various requirements for functionality. HIFWPU have been widely developed in textile, furniture, automobile, and aerospace applications.

Ideal halogen-free instinct flame-retardant waterborne polyurethanes have high flame-retardant efficiency, environmental friendliness, fine compatibility, and good thermostability.     

Lipomatous meningioma: Diagnostic pitfalls and pathological updates

We present a case of histologically confirmed lipomatous meningioma, the first to our knowledge reported in Hong Kong. A 75‐year‐old woman presented to us with on and off dizziness for 1 month. Computed tomography (CT) of the brain showed an extra‐axial mass lesion containing fat and solid enhancing foci at her right frontal region. The definitive diagnosis could be made preoperatively. Postoperative histological examination of the tumour revealed the diagnosis of lipomatous meningioma. We have reviewed the literature and discussed the diagnostic clues, clinical presentation and pathology of this rare tumour.     

HLA-肽四聚体和过继性免疫疗法在防止巨细胞病毒疾病中的应用

背景：抗病毒药物能减少早期的巨细胞病毒疾病,但有较强的毒性和引起晚期巨细胞病毒疾病发生的可能。为了更好地防治巨细胞病毒疾病,研究细胞毒性T淋巴细胞控制巨细胞病毒再活化的作用是很关键的,荧光HLA-肽四聚体是一个很好的工具,被用来监测移植受者的巨细胞病毒特异细胞毒性T淋巴细胞的恢复。 目的：探讨HLA-肽四聚体和过继性免疫疗法在治疗巨细胞病毒疾病中的作用。 方法：由第一、二作者检索2003/2009 PubMed数据库及万方数据库有关移植后巨细胞病毒特异细胞毒性T淋巴细胞检测、抗病毒药物应用、HLA肽四聚体应用、过继性免疫治疗作用的文献,英文检索词为“HLA-peptide tetramers, cytomegalovirus, specific CTL, adoptive immunotherapy”,中文检索词为“HLA-肽四聚体,巨细胞病毒,特异细胞毒性T淋巴细胞,过继性免疫治疗”。排除重复性研究,纳入29篇归纳总结。 结果与结论：用巨细胞病毒特异细胞毒性T淋巴细胞进行的过继性免疫治疗是非常完美的策略,然而,产生这些细胞是昂贵和耗时的,因此治疗不是在每个移植中心都能进行。用HLA-肽四聚体从巨细胞病毒血清阳性供者外周血中选择巨细胞病毒特异细胞毒性T淋巴细胞是非常有希望的策略,使过继性免疫疗法更容易进行。 关键词：HLA-肽四聚体;过继性免疫治疗;巨细胞病毒疾病;特异T细胞;细胞毒性T淋巴细胞     

Vision improvement in a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy

In this report, we describe a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy. The family carried a mitochondrial DNA mutation (mtDNA m.14484T>C) associated with spontaneous visual improvement. A 15-year-old boy from this family was diagnosed with Leber's hereditary optic neuropathy 6 months after losing his vision. His vision recovered after 8 months of supportive treatment. His mother, older brother, and two sisters also had the same mutation and had previously experienced vision loss. In this family, there was no male predominance.