2016年 · 第54卷第08期

Epstein-Barr virus (EBV) is a herpes virus that is pathogenic to humans, and EBV infection is very prevalent worldwide. According to the survey data of 1980s in China, the positive rate of serum EBV antibody in children aged 3~5 years is 80.7% ~100%, and it has increased to 100% by the age of 10 years^[1]。 Most EBV primary infections are acute and mostly asymptomatic, especially children under 6 years of age mostly present with latent or mild onset, but in childhood, adolescence and adolescence about 50% of primary infections present as infectious mononucleosis (leaflet). In some children, the virus continued to move after infection and progressed to severe EBV infection. Severe EBV infection is a serious threat to children's life, which needs to be paid attention by clinicians. Severe EBV infection refers to EBV infection that causes one or more organ dysfunction or has progressed to EBV-associated hemophilocytic lymphohistiocytosis (EBV-HLH), with a mortality rate of more than 50%^[2]A small number of children with EBV infection may develop chronic or recurrent leaflet-like symptoms and develop chronic active Epstein-Barr virus infection (CAEBV). EBV is closely related to the occurrence of nasopharyngeal carcinoma, lymphoma, gastric cancer and other tumors. EBV-related tumors are prevalent worldwide, so it is necessary to improve the diagnosis, treatment and long-term management of EBV infection in children. "Recommendations on principles for the diagnosis and treatment of major non-neoplastic Epstein-Barr virus infection-related diseases in children"^[3]The aim is to standardize the management of non-neoplastic EBV infectious diseases and pay attention to severe EBV diseases.

Epstein-Barr virus (EBV) belongs to the family Herpesviridae and belongs to the subfamily Gamma. It is a herpes virus that trophs human lymphocytes. It was developed by Epstein et al. in 1964^[1]First found in lymphoma tissue cultures in African children. EBV infection is very prevalent in the population, with more than 90% of adults serum positive for EBV antibodies. EBV is mainly transmitted through saliva and can also be transmitted through blood transfusion. Primary EBV infection refers to the initial infection with EBV. According to foreign data, most children under the age of 6 show non-specific manifestations such as asymptomatic infection or only upper respiratory symptoms, but about 50% of adolescents show infectious mononucleosis (IM)^[2]。 After primary EBV infection, the virus establishes latent infection in memory B lymphocytes and carries the virus for life. In rare cases, EBV can infect T lymphocytes or NK cells, resulting in persistent active infection, causing EBV-associated lymphoproliferative disease. EBV reactivation means that when the body's immune function is inhibited and triggered by some factors, latently infected EBV is activated to produce viral replication, causing viremia, and high copies of viral nucleic acids can be detected in peripheral blood. EBV reactivation can cause corresponding clinical manifestations, or it can be a concomitant phenomenon of the original disease.

congenital adrenal hyperplasia (CAH) is a group of autosomal recessive hereditary diseases caused by defects of various catalytic enzymes at various stages of the adrenal cortical steroid synthesis pathway, mainly causing corticosteroid synthesis disorders. The most common CAH is 21-hydroxylase deficiency (21-OHD), which has the risk of fatal adrenal salt loss crisis, and hyperandrogenemia causes growth and gonadal axis disorders. However, there is a definite drug treatment for this disease. Developed by experts of the Endocrine Society Clinical Guidelines Subcommittee in 2010 and issued 21-OHD Clinical Practice Guidelines^[1]。 Experts from the Endocrinology, Genetics and Metabolism Group of the Pediatrics Branch of the Chinese Medical Association refer to the above clinical practice guidelines and combine the evidence-based basis for the diagnosis and treatment of 21-OHD at home and abroad to formulate this consensus on clinical diagnosis and treatment, which provides a reference for domestic pediatric endocrinology and related medical professionals to standardize and optimize the clinical diagnosis and treatment of 21-OHD in China.

Female, 4 d, was admitted to the Department of Neonatology, Liuzhou Maternal and Child Health Hospital, Guangxi Zhuang Autonomous Region in 2013 because of "1 d poor feeding". The child was the second child and the second child, delivered naturally at 41 weeks, with a birth weight of 2 850 g, no special birth history, parents were not intimate married, and there was no abnormal family history. 3 days after birth, the child showed poor feeding, no vomiting, abdominal distension, no fever, convulsions, cough, etc. Physical examination at admission: mental and reactive, slight shortness of breath, mild inspiratory three-concave sign, no rales in the lungs, heart rate 152 beats/min, uniform rhythm, grade 3/6 systolic murmur in the precordial area, liver palpable 4 cm below the right rib, soft in texture. Auxiliary examinations: blood routine, C-reactive protein (CRP), cerebrospinal fluid examination was normal, blood culture was negative, chest X-ray: both lung texture increased, heart shadow increased (cardiothoracic ratio 0.72), heart color ultrasound: patent foramen ovale, mild to moderate tricuspid regurgitation, pulmonary hypertension. Treatment and diagnosis: The child was treated with piperacillin and tazobactam for anti-infection. On the second day of admission, the child developed shortness of breath, fine wet rales could be heard in the lungs, and the heart rate fluctuated between 160 and 180 beats/min. Considering heart failure, the child was treated with cardiotonic, diuretic, and circulation improvement. Because the child is not feeding well, the possibility of intracranial lesions is not excluded, and the head CT is examined (Figure 1) Tip: A circular slightly high-density shadow about 2.2 cm ×2.2 cm in size can be seen behind the third ventricle, with uniform density, CT value about 36 Hu, smooth boundary, the posterior edge is connected with the triangular dilated straight sinus and sinus sinus, showing a "dumbbell" shape, the transverse sinus is also dilated, the adjacent quadrids and the fourth ventricle are occluded, small stripes of slightly high-density shadows can be seen in the suprasellar cistern area, the bodies of bilateral lateral ventricles and the third ventricle are slightly full, small stripes of high-density shadows can be seen below the cranial plate in the left parieto-occipital region, and the posterior longitudinal fissure of the cerebrum is local density. Further examination of head CT angiography (CTA) (Figure 1): The great cerebral vein was quasi-circular dilated, with a diameter of 2.2 cm. The posterior cerebral artery (terminal branch of basilar artery) was injected into the great cerebral vein from its right rear. The straight sinus, sinus sinus and transverse sinus behind the great cerebral vein were all cystic-columnar dilated, with a transverse diameter of about 0.95 cm at the widest point. The sigmoid sinus, subpetrosal sinus and internal jugular vein were dilated and tortuous, and abnormal vascular communication was seen around them. The cerebral artery ring was still intact, slightly compressed and moved downward. The vertebral artery, basilar artery and right internal jugular vein were slightly tortuous, and there was no obvious abnormality in the left internal carotid artery. Diagnosis: Malformation of the great cerebral veins. On the 7th day of admission, the child's condition worsened, and he was treated with ventilator-assisted ventilation. Later, due to the serious condition, the parents asked for automatic discharge. After 1 week of discharge, the child died.

The Ebola outbreak in Africa is not over yet, and another outbreak of the virus called Zika has emerged in the Americas. Following the global warning on Zika virus issued by the Pan American Health Organization (PAHO) on December 1, 2015, the U.S. Centers for Disease Control and Prevention announced on February 8, 2016 that the alert and emergency level for Zika virus was raised to the highest level. The epidemic situation, biological characteristics and clinical characteristics of Zika virus disease are introduced.

Epstein-Barr virus (EBV) is a DNA virus belonging to the gamma subfamily of human herpesviruses, which can invade B lymphocytes as well as T cells and NK cells of the host^[1]。 EBV infection is widespread worldwide, and more than 90% of adults test positive for EBV antibodies. It is mainly transmitted through saliva, but also through blood transfusion^[1]。 EBV infection can lead to a variety of lymphocyte proliferative diseases, including non-neoplastic proliferative diseases, including infectious mononucleosis (IM), chronic active Epstein-Barr virus infection (CAEBV), Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH), and neoplastic diseases; The latter includes Burkitt's lymphoma (BL), hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), nasopharyngeal carcinoma (NPC), etc., as well as lymphoproliferative disease (LPD) that occurs in immunodeficient patients after EBV infection^[1,2]。 The above EBV-related diseases are mostly malignant tumors with extremely poor prognosis and difficult treatment except IM with extremely low mortality rate and good prognosis. Traditional surgery, chemotherapy and radiotherapy have poor curative effect on these malignant tumors and lead to serious adverse reactions. Therefore, it is urgent to find new treatment strategies. In recent years, with the in-depth research on the relationship between human immune system and EBV, immunotherapy has been widely used in the treatment of EBV-related diseases. This article will review the development and application status of immunotherapy for EBV-related diseases at home and abroad.

human cytomegalovirus (HCMV) can encode a variety of mature microRNAs (miRNAs) to regulate the expression of its own and host genes, affect virus replication and participate in various immune escape mechanisms, which is very important for the realization of lifelong latent infection of virus. HCMV infection rate is high in China, and the positive rate of IgG antibody in pregnant women is over 95%. Both primary infection or latent infection can cause intrauterine HCMV infection, resulting in miscarriage, stillbirth, fetal malformation and growth retardation^[1,2]。 Most children with congenital HCMV infection have no obvious clinical symptoms, but some children still have mental retardation, sensorineural deafness and motor dysfunction in the later stage; The infection rate of HCMV in infants and young children in China is 60% ~80%. After the initial acute infection, it turns into a lifelong latent state. When the human immune function is low, HCMV can be activated again, causing a series of clinical symptoms^[1]。 The role of HCMV-encoded miRNA in viral latency mechanism is reviewed.

spinal muscular atrophy (SMA) is a common autosomal recessive genetic disease in childhood, which is mainly manifested by progressive and symmetrical muscle weakness and atrophy of limbs and trunk. Severe children often die of respiratory failure. The incidence of this disease in live births is about 1/6 000 to 1/10 000, and the carriage rate of SMA in Chinese population is about 1/42^[1]。 Homozygous deletion or compound heterozygous mutation of survival motor neuron 1 (SMN1) (i.e. deletion of one SMN1 gene and point mutation of another SMN1 gene) caused the decrease of SMN protein expression is the main pathogenic mechanism of SMA, and the existence of SMN2 gene, which is highly homologous to SMN1 gene, brings a glimmer of hope for SMA treatment^[2]。 In the past decade or so, a variety of therapeutic studies based on increasing the expression of SMN protein have been carried out one after another, and some of the drugs used in SMA have entered the clinical trial stage and made considerable progress. The latest research progress of SMA treatment and the clinical trials of related drugs are reviewed.

Pierre-Robin syndrome (PRS)^[1]The main manifestations are mandibular hypoplasia (micrognathia or jaw retraction), tongue fall and airway obstruction. 58% ~90% of children are accompanied by cleft palate or high palatal arch, and severe cases may have breathing and feeding difficulties. The malformation may exist alone or may be characteristic of congenital malformations such as Stickler syndrome, Velocardiofacial syndrome, Treacher-Collins syndrome, etc. Sleep-disordered breathing (SDB) in children mainly includes primary snoring, upper airway resistance syndrome, obesity hypopnea syndrome, obstructive sleep apnea hypopnea syndrome and central sleep apnea syndrome. PRS is a high risk factor for SDB^[2]。 The mechanism of developing SDB in children with PRS and the relationship between PRS and SDB are reviewed in order to raise everyone's awareness and vigilance.

When conducting clinical research around the diagnosis, treatment, prognosis and etiology of diseases, the goal can be simply summarized as "better understanding diseases and providing valuable clinical decision-making evidence for clinicians". The goals of excellent clinical research: (1) the research evidence level is very high, providing a higher level of clinical evidence for humans; (2) The research quality is reliable and the sample size is large, which lays the foundation for defining a certain understanding; (3) Brand new questions are raised, which may be able to open up a new field of research.