2016年 · 第54卷第06期

For many years, Chinese pediatricians have been paying attention to the clinical diagnosis, treatment and prevention of congenital adrenal hyperplasia (CAH), and have accumulated certain diagnosis and treatment experience. Since 1990s, neonatal CAH screening has been carried out in China. Up to now, nearly 100 neonatal screening laboratories have carried out CAH screening, and the prevalence data have been obtained^[1,2]Through active treatment, the neonatal mortality rate has been reduced, the sex misjudgment caused by the masculinization of the external genitalia of female infants has been reduced, the growth and development have been improved, and good social benefits have been achieved. However, as a relatively complex monogenic genetic disease, in clinical practice, we found that some children with CAH went to the neonatology department, NICU, PICU, pediatric care department, endocrinology department, pediatric internal medicine department, urology department, etc. due to certain symptoms or signs, and were sometimes mistaken for other diseases, resulting in misdiagnosis, missed diagnosis, mistreatment or improper treatment. In order to improve the understanding and prevention ability of CAH, a treatable and preventable disease, this issue publishes the Consensus on Neonatal Screening of Congenital Adrenocortical Hyperplasia (hereinafter referred to as the "Consensus") written by experts from the professional group of Chinese Association of Preventive Medicine, Chinese Medical Doctors Association and Chinese Medical Association, which provides CAH screening and early diagnosis and treatment standards for clinicians and neonatal screening centers. The author puts forward the following problems that should be paid attention to on how to further strengthen the newborn screening of CAH and improve the level of diagnosis and treatment.

congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic disease. Due to the congenital defects of certain enzymes (such as 21-hydroxylase, 11 β-hydroxylase, 3 β-hydroxysteroid dehydrogenase, etc.) in the process of steroid hormone synthesis, adrenal cortex function is reduced, and some children are accompanied by electrolyte disorders and gonadal dysplasia. 21-hydroxylase deficiency (21-OHD) is the most common cause of CAH, accounting for 90% to 95%^[1,2]； The incidence rate reported at home and abroad is 1/10 000~1/20 000^[1,3,4]。 Some children may be life-threatening due to adrenocortical crisis in the neonatal period.

Since the discovery and confirmation of copy number variations (CNV) in the early 2000s that can cause human genetic diseases^[1]Genomic diseases, as an important class of genetic diseases, have received more and more attention. In Europe and America, chromosome microarray analysis (CMA) has become a routine clinical genetic diagnostic tool. Following the release of the CMA Guidelines (October 2010) of the American College of Medical Genetics and Genomics (ACMG) Expert Committee^[2]Canada, Australia, France, Belgium and other countries have successively issued their respective relevant CMA clinical application guidelines or consensus^[3,4]。 In 2014, the U.S. Food and Drug Administration approved the Affymetrix CytoScan Dx chip for clinical testing for the first time, providing a standardized product for the clinical application of chromosome chips. In recent years, the clinical application of CMA in China has been gradually promoted, providing accurate molecular diagnosis for many patients with genetic diseases. It is worth noting that because this technology is a complex clinical testing item, involving many important links such as clinically applicable indications, chip requirements, experimental process and quality control, data analysis, chip result verification, clinical relevance interpretation, patient genetic counseling and translational research, there are many irregularities in the clinical application of CMA in China. Therefore, the Medical Genetics Branch of Chinese Medical Doctors Association, the Clinical Genetics Group of the Adolescent Medicine Professional Committee of Chinese Medical Doctors Association, and the Endocrine Genetics and Metabolism Group of the Pediatrics Branch of Chinese Medical Association organized experts to exchange and discuss all aspects of CMA technology, and formed an expert consensus to standardize and guide the clinical application of this technology, in order to better give full play to the clinical detection effect of CMA in pediatric genetic diseases, improve the scientificity, accuracy and reliability of technical operation and data analysis, and provide guidance and basis for more laboratories to carry out CMA clinical testing. In addition, it is particularly suggested to establish a public data sharing platform through expert consensus, which can better understand the relationship between genomic imbalance and clinical phenotype of Chinese population, and provide a more reliable basis for clinical interpretation of CMA test results.

The child was a 5-year-old male. He was admitted to the Department of Pediatrics, Heart Center, First Affiliated Hospital of Tsinghua University in June 2015 due to "repeated tachycardia for 2 months". The child had two recurrent attacks of tachycardia within 2 months, accompanied by abdominal pain, chest tightness and dizziness. At the time of attack, the electrocardiogram showed wide QRS wave tachycardia, uniform QRS wave and ventricular rate of 223 beats/min. Each time lasting about half an hour, intravenous bolus injection of propafenone converted to sinus rhythm, and the ECG showed complete right bundle branch block. Intracardiac electrophysiological examination in an external hospital showed atrial tachycardia and sinus node dysfunction. Previous ventricular septal defect repair at the age of 1 year. Birth history and past history are not special. The child was the first child, the father (33 years old) and the mother (32 years old) were healthy, and the family history of syncope and sudden death was denied. Physical examination at admission: temperature 36.3 ℃, pulse 85 beats/min, breathing 24 beats/min, blood pressure 105/78 mmHg (1 mmHg =0.133 kPa). Moderate development, clear consciousness, rosy lips, steady breathing, clear breathing sound. Surgical incision scar can be seen on the right chest wall, no bulge in the precordial area, untouched tremor, small heart boundary, uniform rhythm, strong heart sound, no heart murmur and pericardial friction sound. There were no abnormalities in the abdomen and nervous system. Auxiliary examination: Electrolytes, myocardial enzymes and cardiac ultrasound were normal. Electrocardiogram showed: heart rate 60 beats/min, sinus rhythm, first degree atrioventricular block (PR interval 0.24 s), complete right bundle branch block (Figure 1)。 Holter electrocardiogram showed total heart beats of 98 067 beats, heart rate of 39-126 beats/min, mean 71 beats/min, sinus rhythm and sinus bradycardia. Sinus arrest occurred frequently, with 80 arrests throughout the day and the longest R-R interval of 2.34 s. Clinical diagnosis: Progressive cardiac conduction disorder (PCCD, including sinus node dysfunction, complete right bundle branch block, first degree atrioventricular block) atrial tachycardia, postoperative repair of ventricular septal defect. The child underwent permanent endocardial single-chamber pacemaker implantation under general anesthesia on 19 June 2015. The pacing mode was VVI, the heart rate was 60 beats/min, and he was given oral antiarrhythmic therapy with sotalol. He was followed up for 3 months without discomfort.

Example 1Male, gestational age at birth31^＋1Weeks, birth weight 1.6 kg, Apgar score 1 min 9, 5 min 10. He was admitted to the Department of Neonatology of Xiangya Hospital of Central South University in October 2015 due to postnatal dyspnea for 20 min. Nasal continuous positive airway pressure (nCPAP) was given, and pulmonary surfactant was supplemented, and dyspnea was improved. On day 5, the right median cubital vein was catheterized through the peripheral central vein (PICC). Chest X-ray showed that the end of the catheter was located at T₂Vertebral body. After catheterization, the child was initiated to receive parenteral nutrition preparation (TPN) 5 ml/h. Frequent blood oxygen saturation decreased at 12 hours after PICC, progressive aggravation of dyspnea, accompanied by pale skin and mucosa, poor circulation at the extremities, and tracheal intubation and mechanical ventilation were performed. Bedside chest X-ray showed that the bilateral lung transparency was lower than that before catheterization. Thoracentesis was performed, and approximately 13 and 27 ml of milky white liquid were withdrawn from the left and right chest cavities, respectively. The child's dyspnea disappeared. Pleural effusion examination shows a large number of fat particles. removing the PICC; Reexamination of chest X-ray was normal, and mechanical ventilation was discontinued. Continued routine treatment, peripheral intravenous nutrition, hospitalized for 15 d, weight reached 1.68 kg, complete gastrointestinal nutrition, transferred to local hospital for treatment.

A 10-year-old girl was admitted to Yuying Children's Hospital affiliated to Wenzhou Medical University in August 2015 due to "fever for 20 days and cough for 3 days". The child developed fever without obvious trigger 20 days ago, with a body temperature of about 39.0 ℃ and a maximum of 40.2 ℃. The fever type was uncertain, and the fever was high, accompanied by chills and chills. Chest CT in other hospital showed abnormalities, tuberculin test (PPD) was positive, and it was proposed to be diagnosed with infection in the lower lobe of left lung, and tuberculosis was first considered; Isoniazid, rifampicin, pyrazinamide and other treatments were given, but the child's body temperature still repeated. Three days before admission, the child developed paroxysmal cough, accompanied by coughing a small amount of white sticky sputum, abdominal pain, uncertain location, and no chest pain. The child was in good health in the past, denied a history of tuberculosis contact, had been vaccinated with BCG, and his parents made a living by collecting waste products. There was no similar medical history in the family, and there was no history of tuberculosis.

The 1-year-old child was admitted to the Affiliated Hospital of Qingdao University in August 2015 due to "fever for 8 days". The child developed fever 8 days before admission, with a maximum of 39.0 ℃, with oral herpes and scattered red rash throughout the body. Blood routine: white blood cells 16.1×10⁹/L, neutrophils 9.9×10⁹/L, lymphocytes 4.7×10⁹/L, hemoglobin 115 g/L, platelets 389×10⁹/L; C-reactive protein (CRP) 72.5 mg/L; Serum alanine aminotransferase 323 U/L and aspartate aminotransferase 256 U/L. 7 days before admission, bulbar conjunctival congestion, red and cracked lips, red rash on trunk and feet, which was maculopapular rash, accompanied by itching, the rash gradually subsided after administration of mometasone furoate ointment, blood routine: white blood cells 14.6×10⁹/L, hemoglobin 104 g/L, platelets 314×10⁹/L, CRP 57.5 mg/L, alanine aminotransferase 57 U/L, aspartate aminotransferase 46 U/L. Cardiac ultrasound showed no abnormalities, and he was suspected of "Kawasaki disease". He was given high-dose gamma globulin infusion twice (7.5 g/time) and aspirin, but he still had fever and was transferred to our hospital.

The 9-year-old and 2-month-old child was admitted to Guangzhou Women and Children's Medical Center in April 2015 due to difficult speech for 1 year, cough and dysphagia for 3 days, and dyspnea for 1 day. On the same day, she was transferred to the pediatric intensive care unit (PICU) after endotracheal intubation and mechanical ventilation due to respiratory failure. In April and November 2014, the children were treated with mechanical ventilation in the local area and our hospital due to respiratory failure. Before and after treatment, they were accompanied by poor speech, and there was no phenomenon of light morning and heavy evening. Family history is not special. Neurology consultation in April 2015, physical examination: ventilator-assisted ventilation, heart rate 90 beats/min, normal blood pressure and body temperature, no abnormalities in the physical examination of heart, lung and abdomen, clear consciousness, normal understanding, expressing needs with gestures, full movement of both eyeballs in all directions, equal size and round pupils on both sides, 3 mm in diameter, sensitive to light reflex, poor occlusion, positive eyelash sign and Bell's sign, poor lip closure force, inability to complete bulging, arthria and swallowing examinations, pharyngeal reflex, tongue extension in the center of tongue muscle without tremor; The rest of the nervous system examination showed no abnormalities. Skull MRI and cerebrospinal fluid examination were normal. No other special treatments were given during PICU.

The 2-year-old child was admitted to the hospital on July 16, 2015 due to "fever and abdominal distension for 2 months, aggravated for 10 days". The child developed fever 2 months ago, with a maximum body temperature of 38.5 ℃, accompanied by abdominal distension, and the child had no cough, runny nose, vomiting and diarrhea. He went to the local hospital, and the abdominal CT showed peritoneal effusion. He was given anti-infective and symptomatic treatment. The child's fever receded and resumed, but the abdominal distension did not relieve. Since then, I have visited many hospitals, but none of them have a clear diagnosis. More than a month ago, he went to the local municipal hospital and was given anti-tuberculosis treatment according to "abdominal tuberculosis?" for 21 days, but the abdominal distension of the child was not relieved. 10 days ago, abdominal distension progressively aggravated, and for further diagnosis and treatment, I went to our hospital. Past history, personal history and family history were not special, and there was no history of drug or food allergy.

epilepsy and mental retardation limited to females (EFMR) is an epileptic disease limited to females, characterized by epileptic seizures, varying degrees of cognitive impairment, and behavioral disorders. By Juberg and Hellman^[1]First reported in 1971, they found 15 patients with epilepsy in a family of epilepsy, all of them female, with or without intellectual disability. 2008 Dibbens et al.^[2]It is reported that the pathogenic gene of EFMR is PCDH19 gene. There are few reports related to this disease in China. The pathogenesis, clinical characteristics and research progress of EFMR are reviewed.

The main principles of mechanical ventilation are to ensure adequate gas exchange, reduce respiratory work, and maintain human-machine coordination while avoiding or mitigating ventilator-associated lung injury (VILI)^[1]。 In the past decades, neonatal mechanical ventilation modalities and strategies have been continuously invented and optimized. In recent years, neuromodulation assisted ventilation (NAVA), which uses diaphragm electrical activity (EAdi) to control ventilation and keep the nerve center trigger and assisted ventilation in maximum synchronization, is an innovative mode for neonatal mechanical ventilation.

neuroblastoma (NB) is an embryonic tumor of the postganglionic sympathetic nervous system, which is the most common extracranial solid malignant tumor in children^[1]。 The onset of NB is early, the degree of malignancy is high, and the prognosis is poor. After induction chemotherapy, 10% ~20% of children still develop refractory NB^[2]。 Although surgical resection, radiotherapy, chemotherapy, and hematopoietic stem cell transplantation involved multiple therapies, the overall survival rate of children with NB has improved, but the clinical prognosis of high-risk children remains poor^[2]Therefore, it is urgent to find new treatment methods to reduce the mortality rate of such children. Ganglioside GD2 belongs to the ganglioside sphingolipid class, which is overexpressed in solid tumors such as NB, Ewing family tumors, osteosarcoma, and restricted expression in other normal tissues. It is theoretically an ideal target for immunotherapy against NB^[3]。 Previous studies mainly focused on the treatment of NB with anti-GD2 monoclonal antibodies. Because the Fc fragment of murine-derived monoclonal antibodies is immunogenic, it causes intense pain after treatment and forces some patients to terminate treatment early^[4,5,6]。 In recent years, GD2-chimeric antigen receptor (CAR) was constructed to transfect immune cells to treat NB^[7]With the characteristics of specifically recognizing tumor associated antigen (TAA) and non-major histocompatibility complex (MHC) restricted killing target cells, it has high application potential in cellular immunotherapy. Based on the recent research achievements of GD2-CAR modified immune cells in the treatment of NB, this paper reviews the construction of GD2-CAR, effector cell selection, vector selection and anti-tumor performance optimization.

The "20th National Pediatrics Academic Conference of Chinese Medical Association" sponsored by the Pediatrics Branch of Chinese Medical Association was held in Xiamen, Fujian Province from September 23-26, 2015. The "6th National Pediatric Clinical Pharmacology Academic Conference" was merged into the "20th National Pediatric Academic Conference of Chinese Medical Association" and the clinical pharmacology special session was held at the same time. The theme of this session is "Standardizing children's medication and safeguarding children's health". The invited speakers included 3 internationally renowned experts and 10 domestic renowned experts, and 17 oral speeches. The main contents of the meeting were as follows:

The diagnostic test is to check the diagnostic efficacy of a certain diagnostic index. A group of patients suspected of a certain disease are evaluated with diagnostic indexes, and the results obtained are compared with gold standards. The sensitivity, specificity, Jorden's index and other parameters of this index are calculated to evaluate the diagnostic efficacy of this diagnostic index. However, in clinical research, we often encounter the comparison of diagnostic efficacy of two diagnostic indexes. At this time, if we compare the differences of sensitivity and specificity between different indexes separately, we often focus on one thing and lose the other, and can't well evaluate the diagnostic efficacy of the two indexes. We usually compare the area (AUC) under the subject's operating characteristic curve (ROC curve), i.e. the larger the area, the higher the diagnostic efficacy of the index. AUC has high discrimination power for predicting the accuracy of specific events, but it also has some limitations. The clinical significance of AUC is unclear. For example, the area under the curve is 0.8, which has no actual clinical significance, and the clinical significance of the area difference between the two indicators is more ambiguous. Therefore, some people have proposed new evaluation indexes: reclassification improvement index (NRI) and comprehensive discrimination improvement index (IDI).