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关键词： Irritability   depression   disruptive mood dysregulation disorder   developmental psychopathology   transdiagnostic  

摘要： Objective: Irritability is an important theme in paediatric psychiatry considering its high frequency in developmental age, its association with negative outcomes and consequently significant public health impact. Present as main or associated feature of several psychiatric diagnoses, irritability represents a challenge for clinicians who try to understand its origin and role in developmental psychopathology. In this review we try to: (1) get an overview of this dimension and its relationship with each of the main neuropsychiatric disorders in paediatric population and (2) provide a summary of currently available instruments to assess irritability in children and adolescents. Method: In this narrative review, an overview of irritability in children and adolescents is proposed focusing on selected literature. Results: Irritability as feature of many paediatric psychiatric conditions has been evaluated by many authors and included in classifications of paediatric psychiatric diseases. Framework of irritability evolved over time and dimension of irritability has been investigated using different tools and methodologies, both qualitative and quantitative. Metrics of irritability as clinical dimension are important in the diagnostic process of paediatric diseases. Conclusion: Investigating the presence of irritability in all children with related disorders is mandatory if we consider the risk for functional impairment and affective and behavioural disorders associated with high levels of irritability. Using rigid threshold in developmental age to differentiate physiological from pathological irritability could lead many children having subthreshold levels of irritability to receive no diagnosis and, consequently, no treatment where instead a dimensional approach to irritability could allow to identify prodromal phase and prevent the evolution towards clinical pathological expressions.

关键词： Hemagglutinin   ICAM-1   IL-6   Vascular endothelium   Lung injury  

摘要： Objective: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. Methods: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. Results: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 mu g/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 mu l of HA (50 mu g/ml and 100 mu g/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. Conclusions: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

关键词： 子宫内膜间质肉瘤   病理特征   鉴别诊断  

摘要： 探讨子宫内膜间质肉瘤的病理学特征及主要鉴别诊断。方法:回顾分析一例子宫内膜间质肉瘤的临床资料、病理学形态及免疫表型,并复习相关文献。结果:该患者术前检查、术中冰冻考虑为子宫肌瘤,术后病理证实为低级别子宫内膜间质肉瘤,行二次手术。镜下见:瘤细胞稍大于正常增殖期子宫内膜间质细胞,大小较一致,异型性小,在子宫壁平滑肌束间浸润,弥漫成片。免疫组化:CD10、Desmin、ER、PR阳性。结论:子宫内膜间质肉瘤临床较为罕见,临床及影像学检查均缺乏特异性,术前诊断困难,低级别子宫内膜间质肉瘤异型性小,术中冰冻切片易误诊,确诊需结合临床、组织病理学及免疫组化综合诊断。

关键词： Non-small-cell lung cancer   Non-small-cell lung cancer   Lung cancer  

摘要： Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.

关键词： COVID-19   SARS-CoV-2   nonhuman primate   elderly   underlying disease  

摘要： The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and life. A useful pathological animal model accurately reflecting human pathology is needed to overcome the COVID-19 crisis. In the present study, COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. Cynomolgus macaques with various clinical conditions were intranasally and/or intratracheally inoculated with SARS-CoV-2. Infection with SARS-CoV-2 was found in mucosal swab samples, and a higher level and longer period of viral RNA was detected in elderly monkeys than in young monkeys. Pneumonia was confirmed in all of the monkeys by computed tomography images. When monkeys were readministrated SARS-CoV-2 at 56 d or later after initial infection all of the animals showed inflammatory responses without virus detection in swab samples. Surprisingly, in elderly monkeys reinfection showed transient severe pneumonia with increased levels of various serum cytokines and chemokines compared with those in primary infection. The results of this study indicated that the COVID-19 cynomolgus monkey model reflects the pathophysiology of humans and would be useful for elucidating the pathophysiology and developing therapeutic agents and vaccines.

关键词： Prostate cancer   Radical prostatectomy   Urine   Metabolomics  

摘要： Prostate cancer (PCa) is associated with cellular metabolism alterations leading to changes of the metabolome. So far, studies investigating these alterations mainly focused on comparisons of metabolite profiles of PCa patients and healthy controls. In the present study we compared for the first time metabo-lite profiles in a significant number of paired urine samples collected before and eight weeks after radical prostatectomy (rPX) in 34 patients with PCa. Our comprehensive non-targeted liquid chromatographic-mass spectrometric metabolomics approach covered > 3000 metabolite ion masses. We annotated 23 metabolites showing significant changes eight weeks after rPX. While the levels of uridine and six acyl-carnitines in urine were increased before surgery, lower levels were detected for 16 metabolites, like e.g. citrate, phenyl-lactic acid, choline, myo-inositol, emphasizing a relevant pathophysiological role of these biomarkers and the associated metabolic pathways. These results have important implications for poten-tial use of metabolome analyses for detection of prostate cancer and related pathologic and molecular features. (c) 2021 Elsevier B.V. All rights reserved.