2017年 · 第97卷第24期

In 2011, the American Academy of Sciences, the American Academy of Engineering, the National Institutes of Health and the American Science Council jointly launched the initiative "Towards Precision Medicine" for the first time^[1]。 But what really attracted widespread attention to precision medicine was the "Precision Medicine Plan" proposed by then-US President Barack Obama in his State of the Union address in 2015. The plan suggested that the government increase funding for medical research, promote individualized genomics research, and develop individual medical plans for patients with cancer and other diseases based on personal genetic information. Precision medicine is based on individualized medicine, applying modern genetic technology, molecular imaging technology, and bioinformation technology to achieve accurate classification and diagnosis of tumors, and formulate personalized tumor prevention, diagnosis and treatment plans^[2]。 Precision medicine is a new medical category that integrates traditional medical methods and modern scientific and technological means, scientifically understands human body functions and the nature of diseases, and maximizes individual and social health benefits with the most effective, safest and economical medical services. Personalized treatment plans tailored to the individual characteristics of each patient are the vision of precision medicine clinical applications.

Insomnia is a common sleep problem. Among adults, 10% ~15% meet the diagnostic criteria of insomnia, and the course of the disease is chronic. Nearly half of severe insomnia can last for more than 10 years^[1]。 Insomnia seriously damages the physical and mental health of patients, affects the quality of life of patients, and even induces accidents such as traffic accidents and endangers personal and public safety, which constitutes a serious burden for individuals and society^[2]。 Domestic and foreign sleep medicine experts have published a number of diagnosis and treatment guidelines related to insomnia, but the time is relatively old, and most of them are only for adults, which fail to cover special groups such as children, the elderly and pregnant women, and pay less attention to related contents such as traditional Chinese medicine and physical therapy. To this end, in October 2015, China Sleep Research Association held a meeting in Beijing, inviting sleep medicine experts from many large tertiary hospitals in China, covering many departments related to sleep medicine (including psychiatry, psychology, neurology, respiratory department, pediatrics, traditional Chinese medicine, etc.) to set up an expert committee on guideline formulation to compile guidelines for the diagnosis and treatment of insomnia suitable for national conditions. After repeated and full demonstration, combined with the existing clinical experience and the latest research results at home and abroad, especially the evidence of evidence-based medicine, the expert group completed the writing of the guide in one year. This guide aims to provide a standardized framework for the diagnosis and treatment of insomnia for clinicians, caregivers, pharmacists and psychologists, especially those related to sleep medicine.

The residual roots and crowns of maxillary molars should be removed and restored without retention. Because of its special anatomical structure, many methods such as crown splitting and knocking are assisted, which increases the risk of maxillary sinus injury and patients' anxiety. At present, high-speed turbines are mostly used in clinical practice for root removal and tooth extraction, which can effectively alleviate this situation. However, this machine is easy to cause damage to the soft and hard tissues around the surgical area, and cases of subcutaneous emphysema have been reported^[1,2]。 Because of its selective cutting of mineralized tissue, ultrasonic osteotome is a cutting equipment widely used in bone tissue surgery in recent years. The new generation of ultrasonic osteotome has added a special cutting head for tooth extraction, which can realize accurate and efficient cutting of tooth root, which is conducive to the protection of soft and hard tissues around the affected tooth. In this study, ultrasonic osteotome was used to perform maxillary molar surgical extraction, and compared with high-speed turbine in the aspects of operation time, patients' intraoperative anxiety, postoperative pain, and the change of alveolar bone width and height, to evaluate the application effect of ultrasonic osteotome in maxillary molar extraction.

A 16-year-old female was admitted to the Department of Endocrinology of Huashan Hospital affiliated to Fudan University in June 2016 due to worsening headache after octreotide acetate microspheres (Shanlong) injection. Menarche in 2011, irregular menstruation, paroxysmal headache with prolonged menstrual cycle in September 2013, local hospital checked fasting blood glucose increased (specific value unknown), cranial magnetic resonance imaging (MRI) found no abnormality. Oral metformin tablets were given for treatment, and blood sugar control was normal. Paroxysmal headache aggravated in January 2014, unable to sleep at the time of attack [Visual Analog Scale (VAS) score 9 points], without nausea and vomiting. Thick hands and feet, hypertrophic lips, weight 73 kg, height 172 cm (father, mother, sister height 169, 162, 156 cm, genetic height 162.5 cm, respectively) were noted in April 2014; Weight gain of 20 kg and height gain of 10 cm in 1 year. Pituitary MRI enhancement (Figure 1) It was found that the sellar region occupied space (2.6 cm ×1.3 cm), invaded the cavernous sinus to the left and surrounded the internal carotid artery, considering an invasive pituitary tumor. Random growth hormone (GH) 166.92 μ g/L, insulin-like growth factor 1 (IGF-1) 1 208 μ g/L (reference value: 220.0-996.0 μ g/L), oral glucose tolerance test (OGTT) indicated that GH could not be inhibited (GH trough value 77.31 μ g/L), and glucose tolerance was impaired (IGT). An aggressive pituitary GH tumor with IGT and thyroid nodules was diagnosed. Treatment with somatostatin analogue (SSA) octreotide acetate microspheres (Shanlong) (20 mg, intramuscular injection every 4 weeks) for 3 months did not alleviate the headache. Randomized GH 79.62 μ g/L, IGF-1 772 μ g/L, pituitary MRI lesions showed no significant reduction (Figure 2)。 In August 2014, transnasal sphenoidal pituitary tumor surgery was performed. The pathology showed GH tumor with high cell proliferation index (MIB-1:8%), suggesting atypical pituitary GH tumor (sellar area). In November 2014 (3 months after surgery), the GH was 13.5 μ g/L, and the IGF-1 was 908 μ g/L, indicating that the biochemistry was not in remission; MRI enhancement showed residual pituitary tumor (Figure 3)。 Octreotide acetate microspheres 20 mg were injected intramuscularly again every 4 weeks. Reexamination of OGTT test 3 months after SSA treatment (January 2015) showed IGT, GH trough decreased to 15.12 μ g/L, and IGF-1 remained at 716 μ g/L; Colonoscopy showed multiple polyps in the colon, and biopsy pathology showed villous adenoma (transverse colon). Colonoscopy polyp removal was performed. In February 2015, it was changed to octreotide acetate microspheres 30 mg intramuscular injection every 4 weeks. The patient's headache did not relieve after treatment. Within 1 week after octreotide acetate microsphere injection, the headache worsened and toothache occurred, but no abnormalities were found in the dental examination. Head chills, fatigue and drowsiness, persistent menopause. Diet therapy can control blood sugar, no further weight gain, and normal blood pressure. In June 2015, he came to the multidisciplinary outpatient clinic of pituitary disease of Huashan Hospital affiliated to Fudan University for further treatment.

A 37-year-old female was admitted to the Department of Otolaryngology and Head and Neck Surgery of the First Affiliated Hospital of Nanchang University for "accidentally eating fish bones for 3 months and finding a neck mass for more than 1 month". The patient accidentally ate fish bone while eating 3 months ago. At that time, he felt pharyngeal pain, which was aggravated when swallowing. There was no dysphagia, no cough, hemoptysis, no blood in sputum, and no sternal tenderness. Then he went to the local hospital and was given a lateral X-ray of the neck, which showed foreign body in the esophagus. Gastroscopic foreign body removal was recommended, but it was not adopted. There was no obvious pain after swallowing rice and drinking vinegar at home, and no examination and treatment were performed thereafter. I accidentally discovered a mass on my neck 1 month ago, the size of my thumb (Figure 1), there was a slight tingling sensation after neck activity, no fever, no hoarseness and other discomfort, so I went to our hospital for treatment. Since the onset of the disease, the mental diet is OK, the urine and defecation are normal, and the weight has not changed significantly. He was usually healthy, but denied the history of surgery and neck trauma.

Consumption hypothyroidism is a rare form of hypothyroidism caused by thyroid hormones in the body being inactivated too quickly and exceeding the rate of normal thyroid synthesis. As a paraneoplastic syndrome, it is most often accompanied by giant infantile hemangioendothelioma, in addition it has been reported in some non-vascular tumors such as fibromas, gastrointestinal stromal tumors. In recent years, it has been found that tyrosine kinase inhibitor (TKI) treatment may also cause this disease.

Pulmonary hypertension is a common clinical condition with complex etiology, which can be caused by a variety of cardiac, pulmonary or pulmonary vascular diseases. When pulmonary hypertension occurs, the pulmonary circulatory resistance increases, the right heart load increases, and finally leads to right heart failure, which causes a series of clinical manifestations^[1,2,3,4]。 The occurrence of pulmonary hypertension is related to the dysfunction of endothelial damage of pulmonary minor arteries, which leads to abnormal production of vasoactive substances and cytokines and directly acts on vascular smooth muscle, further promoting vasoconstriction. In addition, the hyperproliferation of smooth muscle cells in the pulmonary artery, the remodeling of extracellular matrix and the activation of inflammatory cells can all contribute to the development of this disease. Endothelin-1, phosphodiesterase, nitric oxide, and cycloprostaglandin signaling pathways are involved in the development of this disease, and many drugs have been developed targeting these targets. It has been found that lipid oxidation is involved in many pathophysiological processes of pulmonary hypertension, such as proliferation of smooth muscle cells, apoptosis of endothelial cells, and inflammatory response^[5]。 The role of oxidative stress and lipid oxidation in the development of various types of pulmonary hypertension and the related mechanisms, as well as the potential therapeutic effects of high density lipoprotein mimetic peptide and microRNA (miR) -193 with high affinity for oxidized lipids on the disease were discussed in this paper.

The report shows that in 2015, the number of new cases of gastric cancer in China was about 679,000, and the number of deaths due to gastric cancer was about 498,000^[1]。 Tumor drug resistance, recurrence and metastasis are important factors that threaten the life of gastric cancer patients, while the heterogeneity of tumor cells produced by tumor stem cells is considered to be one of the possible causes of tumor drug resistance, recurrence and metastasis^[2]。 Gastric cancer is a kind of heterogeneous tumor. High-throughput gene sequencing of gastric cancer samples classifies gastric cancer into four categories: microsatellite unstable, Epstein-Barr virus infected, genome stable and chromosome unstable^[3]。 It is generally believed that there are stochastic models and hierarchical models for the production of tumor cell heterogeneity^[4]。 The random mutation model is derived from the clonal evolution hypothesis of tumorigenesis, which refers to a series of gene changes related to proliferation and differentiation in normal cells, including overexpression of proto-oncogenes and downregulation of tumor suppressor genes, which can lead to the occurrence of tumor cells, and then produce tumor cells carrying different gene imprints^[5]。 The hierarchical model is derived from the theory of cancer stem cells, which believes that tumors can be produced by a small number of cells (cancer stem cells). This group of cells is similar to normal human stem cells, and has the ability of self-renewal and infinite differentiation and proliferation. The upstream cancer stem cells re-differentiate the downstream progenitor cells, and then produce differentiated tumor cells with relatively weak proliferation ability^[6]。 However, these two theories are inadequate in explaining the malignant biology of tumors, so it is possible to integrate these two theories to understand tumorigenesis.

The results of the Human Genome Project show that less than 2% of RNA in human genes encode proteins, and the rest are non-coding RNA (ncRNA). According to the length of the ncRNA, the ncRNA is divided into small non-coding RNA and long non-coding RNA (lncRNA), the latter of which has a base length between 200 and 100 000 nt^[1]。 lncRNA is widely found in the nucleus and cytoplasm of eukaryotic organisms, lacking an obvious open reading frame, and having no or little protein coding function. Studies show that^[2]lncRNA can be involved in the pathophysiological processes of many diseases through many different mechanisms such as transcriptional interference, X chromosome inactivation, genomic imprinting, and intranuclear trafficking. It has been shown that lncRNA expression profiles change with disease progression^[3]At the same time, lncRNA can exist in peripheral blood, such as plasma, serum, etc., and circulating lncRNA can stably exist in harsh environments such as repeated freezing and thawing, long-term storage at room temperature and acid-base treatment, and can even be protected from the degradation of endogenous ribozymes^[4,5]。 At present, circulating lncRNA has shown unique value in the early diagnosis and prognosis of many diseases, and its research as a potential marker of various diseases has also become a research hotspot. In this paper, the progress and problems of circulating lncRNA in disease diagnosis are reviewed.