Volume 05 · Issue 04 · 2019

《健康中国行动（2019-2030年）》指出，慢性非传染性疾病目前是中国死亡的主要原因，也是中国最大的疾病负担。心脑血管疾病、癌症、慢性呼吸道疾病、糖尿病、其他慢性非传染性疾病导致的死亡占总死亡人数的88%，占总疾病负担的70%以上。¹在我国，慢性呼吸道疾病的三大主要原因是严重的空气污染、吸烟和二手烟以及重大的急性呼吸道疾病。在一篇发表于柳叶刀2019年6月，周等人²报道称，中国死亡率最高的前四种疾病分别是脑卒中、缺血性心脏病、肺癌、慢性阻塞性肺病（COPD）。其中两个与呼吸系统直接相关。很明显，为了成功预防和治疗呼吸系统问题，中国的呼吸系统和相关部门面临着巨大的压力。

Gene diagnosis refers to the use of genetic testing in the diagnosis of inheritable conditions, which has gradually been applied in clinical practice with the completion of the gene sequencing efforts of the Human Genome Project and the advancement of gene detection technology. In the specialty field of cardiology, monogenic cardiovascular diseases are defined as monogenic inherited diseases with cardiovascular damage as the only phenotype, or accompanied by cardiovascular damage. Although the incidence of such diseases is relatively low, in the country of China with its vast population of 1.33 billion, the sheer volume of patients with monogenic cardiovascular diseases is alarming. With early onset, severe symptoms, and poor prognosis, delays in diagnosis and treatment of monogenic cardiovascular diseases often have serious consequences. Gene testing is perfectly suited for early diagnosis of monogenic cardiovascular diseases, especially for "pre-symptomatic" diagnosis. In this article, we generally review the characteristics of common monogenic cardiovascular diseases, summarize the progress of the standardized application of gene testing technology in clinical practice, describe the applicable population and condition of genetic testing for different monogenic cardiovascular diseases, analyze the practicality of genetic diagnosis of these inheritable conditions, and provide guidance on identifying suitable candidates for gene diagnosis. In conclusion, gene diagnosis provides new insights into the way physicians diagnose diseases, and is well-positioned to guide clinical decision making and treatment, especially in cardiology.

Owing to early diagnosis and rapid development of treatments for cancers, the five-year survival rate of all cancer types has markedly improved worldwide. Over time, however, there has been an increase in the number of cancer patients who develop coronary artery disease (CAD) due to different causes. First, many risk factors are shared between cancer and CAD. Second, inflammation and oxidative stress are common underlying pathogeneses in both disorders. Lastly, cancer therapy can result in endothelial injury, coronary artery spasm, and coagulation, thereby increasing the risk of CAD. As more cancer patients are being diagnosed with CAD, specialized cardiac care should be established to minimize the cardiovascular mortality of cancer survivors.

Translational medicine is a new medical model that has emerged over the past 20 years and is dedicated to bridging the gap between basic and clinical research. At the same time, the diagnosis and treatment of digestive diseases, especially gastrointestinal endoscopy, have been rapidly developed. The emergence of new techniques for gastrointestinal endoscopy has changed the therapeutic spectrum of some diseases and brought huge benefits to patients. Targeted therapy has positively affected the individualized and precise treatment of patients with advanced gastrointestinal cancer. The construction of a standardized biobank provides a strong guarantee for clinicians to conduct translational medical research. Translational medicine has brought good development opportunities, but it also faces challenges. The training of translational medicine researchers and the transformation of educational models require sufficient attention for further development.

Helicobacter pylori (H. pylori) infection is associated with various gastric and extra-gastric diseases. Importantly, this infection is the strongest known risk factor for gastric cancer (GC). H. pylori eradication can effectively prevent H. pylori infection-associated diseases in H. pylori-positive patients, including children and elderly subjects. However, a limited selection of antibiotics, a higher reinfection rate, and certain spontaneous clearance rates, to some extent, restrict the choice of H. pylori treatments in pediatrics. In addition, it is imperative to perform an accurate diagnosis of H. pylori infection in children by determining the presence of the H. pylori infection and the underlying cause of symptoms. In elderly patients, poor tolerance to drugs and higher sensitivity to adverse effects are major concerns during H. pylori therapy. Recent studies have demonstrated that H. pylori eradication could significantly lower the GC risk in the elderly population. The benefit and risk of H. pylori eradication in elderly patients should be comprehensively considered and balanced. If available, susceptibility-based tailored therapies may be preferable in eradicating H. pylori. In addition, to increase the eradication rate and reduce adverse effects, new therapeutic strategies (e.g., probiotic supplementation, berberine supplementation, dual therapy) for H. pylori infection are being extensively investigated. The impact of H. pylori eradication with antibiotics on the microbiota in children has been explored, but further high-quality studies are crucial to delineate the extent of H. pylori eradication affecting the microbial community in children. In this review, we summarize the current understanding of H. pylori diagnosis and treatment in children and the elderly population and aim to provide insights into the efficient management and treatment implementation in these populations.

Long non-coding RNAs (lncRNAs) have critical roles in the development of many diseases including kidney disease. An increasing number of studies have shown that lncRNAs are involved in kidney development and that their dysregulation can result in distinct disease processes, including acute kidney injury (AKI), chronic kidney disease (CKD), and renal cell carcinoma (RCC). Understanding the roles of lncRNAs in kidney disease may provide new diagnostic and therapeutic opportunities in the clinic. This review provides an overview of lncRNA characteristics, biological function and discusses specific studies that provide insight into the function and potential application of lncRNAs in kidney disease treatment.

Despite tremendous efforts to fight cancer, it remains a major public health problem and a leading cause of death worldwide. With increased knowledge of cancer pathways and improved technological platforms, precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes. Nevertheless, a primary cause of unsuccessful cancer therapy remains cancer drug resistance. In this review, we summarize the broad classes of resistance to cancer therapy, particularly pharmacokinetics, the tumor microenvironment, and drug resistance mechanisms. Furthermore, we describe how bacterial-mediated cancer therapy, a bygone mode of treatment, has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies. Through genetic engineering, we discuss how bacteria can be potent anticancer agents given their tumor targeting potential, anti-tumor activity, safety, and coordinated delivery of anti-cancer drugs.

Ten-eleven translocation (TET) methylcytosine dioxygenases catalyze the oxidative reactions of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC), which are intermediate steps during DNA demethylation. It is reported that somatic mutations of TET2 gene are identified in a variety of human tumors, especially in hematological malignancies. The tendency and mechanism of cellular differentiation in different systems are affected by TET2 via regulation of associated gene expression or maintenance of demethylated state. TET2 acts as a critical driver of tumorigenesis through the conversion of 5-mC to 5-hmC and successive oxidation products. Sometimes, it requires special interactions and cofactors. Here, we reviewed recent advances in understanding the function of TET2 proteins in regulating cell differentiation, and its role in various tumors focusing on several digestive cancers.