Red flags for early recognition of adult patients with PTEN Hamartoma Tumour Syndrome

Patients with PTEN Hamartoma Tumour Syndrome (PHTS) are at increased risk of developing cancer. Many adult PHTS patients are not recognized as such and do not receive the cancer surveillance they need. Our aim was to define phenotypic characteristics that can easily be assessed and manifest by early adulthood, and hence could serve as red flags (i.e. alerting signals) for early recognition of adult patients at high risk of PHTS. Phenotypic characteristics including macrocephaly, multinodular goitre (MNG), and oral features were examined in 81 paediatric and 86 adult PHTS patients by one of two medical experts during yearly surveillance visits at our Dutch PHTS expert centre between 1997 and 2020. MNG was defined as signs of thyroid nodules and/or goitre. Oral features included gingival hypertrophy, high palate (adults only) and oral papillomas. Based on the characteristics’ prevalence in different age groups, combinations of phenotypic characteristics were defined and evaluated on their potential to recognize individuals with PHTS. Macrocephaly was present in 100% of paediatric and 67% of adult patients. The prevalence of MNG was ∼50% in paediatric and gradually increased to >90% in adult patients. Similar percentages were observed for any of the oral features. Scoring two out of three of these characteristics yielded a sensitivity of 100% (95%CI 94–100%) in adults. The presence of the combination macrocephaly, MNG, or multiple oral features could serve as a red flag for general practitioners, medical specialists, and dentists to consider further assessment of the diagnosis PHTS in adults. In this way, recognition of adult PHTS patients might be improved and cancer surveillance can be offered timely.     

Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment

Background

We report the utility of combining lung sound analysis and fractional exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation in patients with bronchial asthma.We investigated the usefulness of the combination of the expiration-to-inspiration sound power ratio in the mid-frequency range (E/I MF) of 200–400 Hz and FeNO for comprehensively classifying disease type and evaluating asthma treatment.

Huntington Disease in Asia

Objective:

The objective was to review the major differences of Huntington disease (HD) in Asian population from those in the Caucasian population.

Data Sources:

Data cited in this review were obtained from PubMed database and China National Knowledge Infrastructure (CNKI) from 1994 to 2014. All the papers were written in English or Chinese languages, with the terms of Asia/Asian, HD, genotype, epidemiology, phenotype, and treatment used for the literature search.

Study Selection:

From the PubMed database, we included the articles and reviews which contained the HD patients’ data from Asian countries. From the CNKI, we excluded the papers which were not original research. Due to the language''s restrictions, those data published in other languages were not included.

Results:

In total, 50 papers were cited in this review, authors of which were from the mainland of China, Japan, India, Thailand, Taiwan (China), Korea, and western countries.

Conclusions:

The lower epidemiology in Asians can be partly explained by the less cytosine-adenine-guanine repeats, different haplotypes, and CCG polymorphisms. For the physicians, atypical clinical profiles such as the initial symptom of ataxia, movement abnormalities of Parkinsonism, dystonia, or tics need to be paid more attention to and suggest gene testing if necessary. Moreover, some pathogenesis studies may help progress some new advanced treatments. The clinicians in Asian especially in China should promote the usage of genetic testing and put more effects in rehabilitation, palliative care, and offer comfort of patients and their families. The unified HD rating scale also needs to be popularized in Asia to assist in evaluating the progression of HD.     

Macrophage Phenotypes and Hepatitis B Virus Infection

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.     

紫杉醇对大鼠肺血管平滑肌细胞表型和细胞骨架的影响

目的 探讨不同浓度的紫杉醇对大鼠肺血管平滑肌细胞增殖的抑制作用及其对细胞骨架和表型转化的影响.方法 采用MTT、[3H]-胸腺嘧啶掺入法检测不同药物浓度紫杉醇对血小板源性生长因子BB( PDGF-BB)诱导的血管平滑肌细胞增殖的影响;采用蛋白质免疫印迹法(Westernblot)对平滑肌α肌动蛋白及平滑肌22α蛋白(SM22α)表达活性进行检测;利用激光共聚焦显微镜观察F-肌动蛋白的改变.结果 与PDGF组比较,紫杉醇药物干预组细胞增殖受到明显抑制,四甲基偶氮唑盐微量酶反应比色法(MTT)检测抑制率分别为40.0％,30.0％,18.0％ (P＜0.01),[3H]-胸腺嘧啶掺入法测得的细胞增殖抑制率分别为45.4％,35.4％,21.6％ (P ＜0.01),平滑肌α肌动蛋白和SM22α表达均升高,细胞骨架F-肌动蛋白的荧光强度明显下降.结论 在PDGF-BB存在的情况下,紫杉醇可剂量依赖性抑制血管平滑肌细胞的增殖,通过作用于微丝细胞骨架促进血管平滑肌细胞由合成型向收缩型转化,进而影响血管平滑肌细胞的增殖.     

心脏型肌球蛋白结合蛋白C基因缺失突变导致肥厚型心肌病特点分析

目的观察肥厚型心肌病（HCM）患者心脏型肌球蛋白结合蛋白C基因（MYBPC3）缺失突变及其表型的特点。方法在100例HCM患者中对MYBPC3的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应（PCR）扩增目的片段,双脱氧末段终止法测序。对突变患者进行家系调查,分析其表型特点。结果在两例先证者中分别发现两个缺失突变14262_14264delAAG和14364delG,均位于外显子25。表型分析发现两例先证者均有劳力性胸闷、胸痛和晕厥史,超声心动图表现为不对称性肥厚（室间隔/左室后壁分别为2.5、3.2）,但SAM征阴性,发病年龄分别为38岁和29岁。结论缺失突变是MYBPC3基因突变的常见形式,14262_14264delAAG或14364delG突变导致的HCM表现为不对称性心肌肥厚,患者容易出现晕厥等症状,应该警惕心源性猝死的发生。     

A Novel Missense Mutation,Leu390Val,in the Cardiac ß-myosin Heavy Chain Associated with Pronounced Septal Hypertrophy in Two Families with Hypertrophic Cardiomyopathy

Objective: An examination of the genetic background and phenotypic presentation of familial hypertrophic cardiomyopathy (FHC) with respect to specific mutations in the MYH7