2018年 · 第56卷第05期

Ten years have passed since the widespread epidemic of hand, foot and mouth disease in China in 2008. Hand, foot and mouth disease is still the Class C infectious disease with the highest incidence and the largest number of deaths in China, which seriously affects children's health. Looking back for 10 years, the epidemic status, disease burden, progress in early identification and diagnosis and treatment of severe cases, and vaccine research and development of hand, foot and mouth disease in China are reviewed.

From the "U.S. -European Expert Consensus" in 1994 to the "Berlin Standards" in 2012 to the "Childhood Acute Respiratory Distress Syndrome (pARDS): Recommendations of the Childhood Acute Lung Injury Consensus Conference" in 2015, the definition, diagnosis and treatment of acute respiratory distress syndrome (ARDS) and pARDS are continuously revised; Coupled with advances in respiratory support technology, the mortality rate of adult ARDS has dropped from 55% to 65% in the 1980s to 35% to 40% today, and the overall mortality rate of pARDS has also dropped to a level similar to that of adults (35%)^[1,2,3]。 However, the mortality rate of severe pARDS is still high. How to solve the dilemma? Where is the way out? The author would like to throw a brick and a jade here.

The basic principle of extracorporeal membrane oxygenation (ECMO) is to drain blood from the body to the outside through arteriovenous cannulation. After artificial membrane oxygenation, oxygenated blood is infused into the body through a pump to maintain the blood supply and oxygen supply of various organs of the body. It can provide long-term respiratory and cardiac support for patients with severe cardiopulmonary failure, so that the patient's heart and lung can fully rest, and win valuable time for further treatment and recovery of cardiopulmonary function^[1]。 According to 2016 data from the International extracorporeal life support organization (ELSO), compared with adults and children, ECMO support for neonatal respiratory diseases has the best prognosis, with an average survival rate of 74%^[2]。 ECMO technique is an effective treatment for neonates whose routine respiratory support techniques are ineffective^[3]。 This expert consensus is for reference only for ECMO support in newborns with respiratory failure.

In 2017, the American Critical Care Association (SCCM) and the American Association for Parenteral and Enteral Nutrition (ASPEN) jointly released a new version of the Guidelines for the Implementation and Evaluation of Nutritional Support Treatment for Critically Ill Children (referred to as the 2017 version of the Guidelines)^[1]The guidelines are revised and updated on the basis of the 2009 version of the guidelines. The new guidelines cover a wide range of contents, including nutritional assessment of critically ill children, energy demand supply, reasonable protein intake, choice of enteral and parenteral nutrition, and immune nutrition support. Now we focus on interpreting the main contents and updated parts of the 2017 version of the guidelines, in order to provide assistance for the standardized treatment of clinical nutrition for critically ill children.

A 3-year-old and 11-month-old male was hospitalized in the Department of Pediatrics, Xiangya Hospital, Central South University in January 2016 due to "repeated convulsions for 8 months". At the beginning of the disease, he showed convulsions after fever: staring at both eyes, closed teeth, cyanosis of the lips, and rigidity and shaking of both upper limbs. The attacks gradually increased, often accompanied by fever, manifested as eyes turning up for tens of seconds, body trembling slightly, followed by rigidity and trembling of limbs, no obvious special growth and development before the onset and past history, and no neurological localization signs in physical examination. EEG showed "extensive 1.0~2.5 Hz spinous slow wave and multi-spinous slow wave emission during sleep period", and Gesell scale showed "gross movement, responding to the critical level of human ability, and the rest was significantly behind normal". Treatment with sodium valproate showed no significant improvement, and 10 attacks occurred within 1 day, each time for more than 20 seconds. Reexamination of EEG showed "background θ rhythm was the main rhythm, a large number of extensive 2.0~4.0 Hz spinous slow wave and multi-spinous slow wave emission, and the waking period was close to continuous emission, obvious in the front of the head, and several isolated and continuous myoclonic attacks were detected" (Figure 1）。 Blood routine, liver and kidney function, myocardial enzymes, electrolyte, blood sugar, blood lactate, blood ammonia and other routine tests were normal. The blood concentration of valproic acid was 58.38 mg/L. Cranial magnetic resonance imaging (MRI), heart and abdomen color ultrasound, bone marrow smear, blood screening, fundus examination and mitochondrial hotspot mutation gene detection were no abnormalities. Levetiracetam (maximum dose 30 mg/kg per day) was added. After that, the child was still hospitalized for cluster attacks many times. In severe cases, he was listless, unable to speak, needed to sit, and often had hand shaking. Adding or switching to topiramate, nitrovalam, piracetam, and ketogenic diet successively, sometimes it can be controlled for 1 to 7 days for a short time, but there are still repeated myoclonic attacks, and the EEG is not improved. Adding clobazam at the age of 4 years and 9 months, convulsions are significantly reduced, and the attacks are 1 to 2 times a month. The results of targeted capture sequencing of epilepsy-related genes suggested that the heterozygous mutation of SCN2A gene c.3955C>T (R1319W) was verified by parents as a newborn mutation, which was not reported in the Human Gene Mutation Database (HGMD) (Figure 2), the mutation is interpreted as suspected pathogenic according to the American Society of Medical Genetics and Genomics (ACMG) guidelines. After that, oxcarbazepine was added to 35 mg/kg per day, and other drugs except clobazam were gradually reduced, and convulsions were obviously controlled. After follow-up until February 2018, there was only one minor attack. Reexamination of EEG showed "background occipital theta rhythm, a small amount of slow waves and sharp slow waves in bilateral hemispheres during sleep". At the same time, the child's cognition was significantly improved, which was basically similar to that of children of the same age, but the speech was slightly vague.

A 7-year-old and 7-month-old male was admitted to the hospital because of "pale complexion for more than 2 years and abnormal renal function for 12 days". Two years ago, the child had a pale complexion without obvious inducement, and he was not treated regularly. He was treated with oral "health products" intermittently. The pale complexion progressively aggravated, so I went to the local hospital 12 days ago. The examination revealed "severe anemia" and "renal failure", and was referred to Guiyang Maternal and Child Health Hospital for further diagnosis and treatment. During the course of the disease, there was no edema, yellow and clear urine, no headache and blurred vision.

A 3-year-old male was admitted to the Department of Pediatrics of the Second Xiangya Hospital of Central South University due to "general fatigue for more than 1 year, cough, fever and wheezing for 3 days". More than 1 year ago, the child developed weakness of both lower limbs without obvious trigger, and needed to be helped to stand up after squatting. He went to many tertiary A-class hospitals in other hospitals successively, and the lactate dehydrogenase 534.1 U/L, creatine kinase 1 819 U/L and creatine kinase isoenzyme 83.3 U/L were checked. No obvious abnormalities were found in myoelectric/evoked potential, hematuria metabolism screening and neuromuscular gene screening. Three months ago, the child's limb weakness was obviously aggravated, and both lower limbs were almost paralyzed, and it rapidly progressed to general weakness. Three days ago, he began to have cough, fever and wheezing, but there was no significant improvement after treatment in the local hospital, so he was hospitalized with "general weakness". Past history and personal history are not special. The parents were in good health and were not married by close relatives. The brother died of general fatigue at the age of 4, denying other familial genetic history.

The 9-year-old child was admitted to the Second Department of Respiratory Medicine, Beijing Children's Hospital affiliated to Capital Medical University in January 2016 due to "repeated bilateral pneumothorax for 1 month". One month ago, the child developed chest pain during physical education class, accompanied by breathing difficulty, no cough and wheezing, no fever, no polydipsia and polyuria. Chest X-ray examination in the local hospital showed bilateral pneumothorax, and subcutaneous puncture, closed chest drainage and other symptomatic treatments were given many times. Reexamination of lung CT showed intrapulmonary vesicles and right pneumothorax. In order to clarify the cause, he was transferred to our hospital for treatment. Three years ago, the child had a history of polydipsia and polyuria. The local hospital improved head CT examination and vasopressin test without water and found no obvious abnormalities. The parents gave traditional Chinese medicine (specifically unknown) orally for about 2 weeks. The symptoms of polydipsia and polyuria disappeared. Family history is not special.

On October 18-22, 2017, the 19th National Pediatric Nephrology Conference was once again incorporated into the kidney special session of the 22nd National Pediatric Academic Conference of Chinese Medical Association and was held in Suzhou at the same time. The conference received 389 submissions, including 14 special lectures, 4 case discussions, 1 English exchange for young people, 34 conference speeches and 350 posters.

With the progress of critical care diagnosis and treatment technology, many children with chronic respiratory failure, such as chronic lung disease, central hypopnea and neuromuscular diseases, can survive for a long time with the support of ventilators. However, long-term hospitalization not only increases medical expenses, but also is not conducive to children's physical and mental health and family social needs. For children with ventilator dependence, the ideal way to do this is to receive care and treatment at home. With the commercialization and refinement of home ventilators, home mechanical ventilation (HMV) is becoming more and more feasible and widely used in western countries. The application of HMV is reviewed in order to improve the understanding of HMV among pediatricians and to accelerate the popularization and application of HMV in children in China.

The ATP1A3 gene is located on chromosome 19q13.2 and encodes Na⁺/K⁺-ATPase α 3 subunit. Na-K-ATPase is a P-type cation transporter that maintains Na⁺and K⁺It plays a key role in the transmembrane electrochemical gradient. The alpha subunit is a catalytic subunit, and there are four subtypes, among which the alpha 3 subunit is mainly expressed in neurons. In 2004, it was discovered that this gene is the cause of rapid-onset dystonia-parkinsonism (RDP)^[1], 2012 Heinzen et al.^[2]It was confirmed that this gene is also the causal gene of alternating hemiplegia of childhood (AHC). With the further study of ATP1A3 gene phenotype, it was found that this gene mutation can lead to a group of phenotypically different neurological disease spectrum, including RDP, AHC and cerebellar ataxia, loss of reflexes, high arch foot, optic atrophy and sensorineural hearing loss (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss, CAPOS) Syndrome, epilepsy, and recently reported recurrent encephalopathy with cerebellar ataxia (relapsing encephalopathy with cerebellar ataxia, RECA)^[3]。 A variety of neurological diseases associated with ATP1A3 gene mutation are described, and the genotype-phenotype correlation of each disease is analyzed.

progressive familial intrahepatic cholestasis (PFIC) is a group of rare heterogeneous autosomal recessive diseases that often onset in the neonatal period or early infant, and is characterized by progressive cholestatic jaundice, intractable pruritus and growth retardation, which can lead to liver fibrosis, cirrhosis and liver failure^[1], is one of the five major causes of liver transplantation^[2]10% to 15% of pediatric liver transplant patients are attributed to this. Before the 1990s, liver transplantation was the only option for children with PFIC who did not respond well to drug therapy, however, transplantation was largely limited by factors such as high cost, lack of organ source, and severe postoperative complications. In addition, about 73% of PFIC-1 children had no improvement or even worsening symptoms such as diarrhea after liver transplantation, and liver steatosis occurred in the early postoperative period, which eventually led to fibrosis of the transplanted liver^[3,4]。 In the past 20 years, non-transplant surgical treatment aimed at reducing the hepatointestinal circulation of bile acids has gradually emerged as an alternative method of liver transplantation, which not only improves the quality of life of children with low glutamyl transpeptidase (GGT) type PFIC, but also achieves good therapeutic effects in preventing disease progression and alleviating clinical symptoms, with a total effective rate of 81% reported^[5]。 There is still no agreement on the choice of surgical methods at home and abroad. Now this review is introduced, hoping to provide help for the choice of clinical surgical options.

next-generation sequencing (NGS) is a new sequencing method compared with the first-generation DNA sequencing technology. In 1977, Frederick Sanger invented the dideoxy chain termination nucleic acid sequencing technology, which made gene sequencing possible and completed human genome sequencing. Sanger sequencing method is called the first generation sequencing technology. Its sequencing accuracy is high, and it has been widely used in PCR products, vector cloning and sequencing. However, Sanger sequencing method also has some defects, such as long sequencing reaction time, low sequencing throughput and high cost. To address this problem, The National Human Genome Research Institute (NHGRI) launched The NGS project in 2004^[1]。 In 2005, an ultra-high-throughput genome sequencing system based on pyrophosphate sequencing was reported, which pioneered NGS^[2]。 The biggest advantages of NGS lie in high throughput, low cost and high sensitivity. It can measure millions or even hundreds of millions of DNA or RNA sequences at the same time, which greatly speeds up the whole genome sequencing, thus greatly reducing the cost of single base sequencing. This completely changed the past research mode, brought new changes to human and animal and plant genomics, transcriptomics, metagenomics and other aspects, and gradually deepened into the field of microbiology research. In order to improve the understanding of this technology, the application of NGS in the field of clinical microbiology is reviewed.

It is the requirement of modern medicine to master the thought of evidence-based medicine and implement it in clinical practice. The development and evolution of evidence-based medicine are presented.