2017年 · 第55卷第03期

Neonatal hypoxic respiratory failure and pulmonary hypertension are critical diseases in the neonatal period, and they are also very challenging clinical problems in respiratory therapy. The understanding of their pathogenesis and treatment strategies have been continuously optimized with the development of neonatal critical care medicine, which fully reflects the development of neonatal medical diagnosis and treatment technology. the diagnosis and treatment of persistent pulmonary hypertension of the newborn (PPHN) comprehensively reflects the latest technologies and achievements in cardiopulmonary circulation, respiratory support, hemodynamic monitoring and evaluation, and selective pulmonary vasodilator application in the postnatal transition. Since the disease was first reported in 1969, its etiology, pathogenesis, diagnostic methods and treatment strategies have made great progress. Especially in the past 20 years, evidence-based medicine has played a great role in the clinical practice of diagnosis and treatment of PPHN in the course of understanding PPHN, and the changes in diagnosis and treatment of this disease have also provided a good learning model for neonatologists.

persistent pulmonary hypertension of the newborn (PPHN) refers to the continuous increase of pulmonary vascular resistance after birth, which causes the transition from fetal circulation to normal "adult" circulation, which causes right-to-left shunt of blood at the level of atrial and/or arterial ducts, and clinical symptoms such as severe hypoxemia. PPHN accounts for about 0.2% of live births, but the proportion of different degrees of pulmonary hypertension can be as high as 10% of all newborns with respiratory failure^[1]And has a relatively high mortality rate. Classical PPHN is more common in term or post-term infants, but in recent years, due to the increased survival rate of very low or ultra-low birth weight infants, pulmonary hypertension complicated by bronchopulmonary dysplasia (BPD) has begun to receive attention. This chronic pulmonary hypertension can occur in the late newborn and is even diagnosed in the pediatric unit after discharge from the neonatal intensive care unit (NICU). Classification of neonatal pulmonary hypertension at the 5th World Pulmonary Hypertension Forum (WSPH) in Nice, France in 2013 highlighted the role of different lung diseases in the development of pulmonary hypertension in the neonatal period^[2]It is divided into: (1) according to the special anatomical and physiological characteristics of the neonatal period, the pulmonary vascular resistance of the child cannot be effectively reduced after birth, that is, the neonatal PPHN; (2) Pulmonary hypertension is based on lung diseases and/or hypoxia, and belongs to the category of developmental lung diseases, such as alveolar, pulmonary blood vessel and connective tissue damage that affect lung development before and after delivery. Pulmonary hypertension complicated by BPD is common. Since 2002, "Diagnosis and treatment routine of neonatal persistent pulmonary hypertension (draft)" was published^[3]Since then, the diagnosis and treatment of this disease has made great progress; In order to further standardize diagnosis and treatment, reference is made to relevant literature and guidelines at home and abroad^[4,5]The Neonatology Group of the Pediatrics Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Journal of Pediatrics organized relevant experts to jointly formulate this consensus.

Neonatal respiratory distress syndrome (RDS) is an important disease in premature infants. Although the treatment is maturing and the survival rate of young premature infants is gradually increasing, the incidence of bronchopulmonary dysplasia (BPD) is also increasing, in part due to the reduction of postnatal hormone use. Since 2006, neonatal experts from many European countries have reviewed the latest literature every three years to reach a consensus on the prevention and treatment of RDS or premature infants at risk of RDS, and are determined to improve the prognosis of European newborns. The European guidelines for the prevention and treatment of RDS began to be published in 2007 and were updated in 2010 and 2013, during which they received strong support from the European Society of Perinatal Medicine. RDS is due to pulmonary surfactant (PS) deficiency leading to early postnatal respiratory distress, and the typical clinical manifestations have changed greatly with the improvement of prevention and treatment. Because of the early use of PS and continuous positive airway pressure (CPAP), it is now difficult to see the typical ground glass appearance and bronchial inflation signs of chest X-rays. Based on blood gas analysis and inhaled oxygen concentration (FiO₂) Diagnosis of RDS has also become redundant, and clinicians tend to adopt a more practical approach, often based on assessment of respiratory work and early postnatal FiO₂Determine whether PS treatment is needed. Therefore, it is quite difficult to count how many children really have RDS. In 2015, the data of 4,142 cases of RDS in Europe were uploaded to the Vermont Oxford Neonatal Collaborative Network in the United States. The incidence of RDS was 80% of premature infants at 28 weeks of gestational age and 95% at 24 weeks of gestational age. In recent years, large-scale clinical trials have shown that about 50% of premature infants with a gestational age of 26 to 29 weeks who receive early CPAP treatment do not need tracheal intubation or PS treatment. The diagnosis of RDS after prophylactic or early PS treatment makes the incidence of RDS high.

nephronophthisis (NPHP) is a group of rare autosomal recessive cystic kidney diseases, which mainly involve the renal tubules and interstitium. It is one of the common causes of end-stage kidney disease in children and adolescents caused by genetic factors^[1]。 NPHP is a group of genetically heterogeneous diseases, and 20 causative genes have been identified^[2,3]。 In 2008, we confirmed the first child with familial juvenile NPHP caused by NPHP1 gene mutation in China, and subsequently identified a number of other NPHP cases caused by NPHP gene mutation^[4]Other domestic units have also reported related cases^[5,6]。 A case of NPHP caused by NPHP3 gene mutation admitted to the Department of Pediatrics of Peking University First Hospital is presented to analyze and explore the diagnostic ideas of hereditary renal cystic lesions, especially NPHP.

A 3-day-old male was seen in West China Hospital of Sichuan University in July 2016 due to "partial skin ulceration and erosion of the trunk and limbs for 3 days". When the child was born 3 days ago, the skin of the head, face, limbs and groin was partially ulcerated and eroded. It was the first birth and the first birth, born naturally, with a gestational age of 36 weeks. The Apgar score was 10 points at 1 and 5 minutes after birth, and there was no trauma during labor. His mother was 36 years old. She went to West China Stomatological Hospital in April 2016 due to "oral erosion for 1 month". She was 24 weeks pregnant at that time and did not undergo pathological biopsy. She completed the detection of peripheral blood anti-desmosome glycoprotein (Dsg) 1 antibody and 3 antibody in our hospital, which were 1.69×10, respectively.⁵U/L (>0.15×10⁵U/L is positive), 1.97×10⁵U/L (>0.1×10⁵U/L was positive), and she was diagnosed as "pemphigus vulgaris". She was treated with oral prednisone (30 mg/d), and the oral lesions were controlled, followed by irregular medication. Her mother's prenatal examination during pregnancy, including syphilis and other venereal diseases, had no abnormalities. Physical examination of the child admitted to the hospital: Some skin absence in the forehead, right upper limb, and groin area revealed a bright red erosion surface, with pustules on the edge, accompanied by a small amount of exudation, and pustular scab (Figure 1), no blisters or erosion in oral and genital mucosa. Laboratory tests: blood, urine, fecal routine, biochemical examination, complete set of tests before blood transfusion were normal; The bacterial culture of the lesion secretion was negative. Anti-DSG1 and Dsg3 antibodies in peripheral blood of children were 0.09×10, respectively⁵U/L, 1.5×10⁵U/L, and the anti-DSG1 and Dsg3 antibodies in peripheral blood of mothers were 1.15×10, respectively⁵U/L, 1.94×10⁵U/L. Histopathology of skin lesion margins in children (Figure 2): epidermal spine intracellular edema; Direct immunofluorescence: interkeratinocyte reticular IgG (+), C3 (+).

A 6-year-old child was admitted to hospital for 10 months due to repeated macroscopic hematuria with lower abdominal pain. Macroscopic hematuria occurred without obvious trigger. He went to Qingdao Municipal Hospital 3 days after the disease. B-ultrasound of urinary tract showed multiple stones in both kidneys. After conservative treatment (a lot of drinking water and stone removal mixture), anti-infection and other treatments, the patient discharged gravel-like stones by himself, and the lower abdominal pain was relieved. Subsequently, the child had repeated episodes of lower abdominal pain with macroscopic hematuria, and occasionally gravel-like stones were discharged in the urine. Previous history of "asthma" in the child for 4 years. The parents of the child are in good health, and they deny the history of inner marriage and family genetic diseases. For further diagnosis and treatment, he visited the Affiliated Hospital of Qingdao University in October 2012.

A 10-year-old woman was admitted to the hospital for "cough for 2 weeks 11 months after the diagnosis of systemic lupus erythematosus". The child visited our hospital 10 days ago when there was a rash between the eyebrows and the root of the nose without obvious trigger 11 months ago. Physical examination showed that there were scattered red rash between the eyebrows and the root of the nose, which was symmetrically distributed and slightly higher than the skin surface, and did not fade or molt when pressed. Serum antinuclear antibody positive (nuclear granular type), titer 1:10 000, anti-SM antibody (+), anti-SSA antibody (+ + +), anti-SSB antibody (+ + +), anti-RO-52 antibody (+ + +), anti-ribonucleic acid protein antibody positive (+ +), anti-ribosomal P protein antibody (+ + +), serum complement C3: 0.86 g/L, C4: 0.093 g/L, alanine aminotransferase 63 U/L, aspartate aminotransferase: 43 U/L. The levels of immunoglobulin G, A, M and renal function were normal, and there were no abnormalities in blood routine, urine routine, lung and head CT. He was diagnosed as systemic lupus erythematosus (SLE), and was discharged after 5 days of treatment with "hydroxychloroquine sulfate 0.15 g/d and prednisone 40 mg/d". Oral hydroxychloroquine sulfate tablets were continued outside the hospital, and oral prednisone was gradually reduced (5 mg every 3 weeks or so). During the reduction process, new rash appeared on the face and lower limbs of the child, and no abnormality was found in many blood routines and urine routines. Cyclophosphamide intravenous pulse therapy was administered while oral hydroxychloroquine sulfate and prednisone were continued with appropriate dose adjustments. This is the sixth cyclophosphamide shock therapy admission to the hospital as planned. One week before admission, the child presented with slight dry cough, no fever, vomiting and diarrhea, good diet and sleep, and normal urine and defecation.

A male child, 2 years old and 8 months old, was admitted to hospital for more than 1 year due to the discovery of a skin mass. The child fell from a chair to the ground 10 days before the onset of the disease, and then appeared a head mass, which was soft and non-tender. After 2 to 3 months, it resolved spontaneously without leaving any traces, and then involved the neck, shoulders and lower back one after another. At the beginning of the disease, the mass was soft and non-tender. After 3 to 4 months, some of the mass resolved spontaneously and some gradually hardened, accompanied by restricted neck movement and progressive aggravation. There was no recurrent fever, rash, joint swelling and pain during the course of the disease. There were no similar cases in the family. The child's growth and development history and vaccination history were normal.

A male, 8 months and 3 days old, was admitted to Jinan Children's Hospital in February 2016 for treatment because of "abnormal urine test found for more than 1 month and runny nose for 1 day". One month before admission, I went to the local hospital due to "diarrhea". Urinary routine: occult blood (+), and no special treatment was given. Later, he went to the outpatient clinic of our hospital due to "cough". Urinary routine: urine protein (+) and red blood cells (high-power field) 3.6/high-power field; Urine transferrin 34.8 mg/L, urine immunoglobulin G 28.9 mg/L, urine microalbumin>341 mg/L, urine α 1 microglobulin 16.1 mg/L, urine β 2 microglobulin 0.28 mg/L, all of which were on the high side. After administration to control upper respiratory tract infection, after 1 week interval, re-examination: urine routine: urine protein (+); urine protein/creatinine ratio 5.24; Urinary transferrin was 20.9 mg/L, urinary microalbumin>341 mg/L, and the rest was normal. During the onset of the disease, the child had pale yellow urine color, no macroscopic hematuria, a little foamy urine, no crying during urination, normal urine output, and was admitted to hospital due to unexplained proteinuria.

Endothelial cells are distributed in the form of monolayer cells at all levels of blood vessels and are distributed in dendritic structure to constitute the endothelial system. In this process, endothelial cells not only play the role of separating blood from peripheral tissues, but also attract much attention for their endocrine, anticoagulant and pathological changes after injury^[1,2]。 However, glomerular capillary endothelial cells are different from other endothelial cells because of their anatomical position, which leads to their special functions^[1,3]。 Through renal biopsy, capillary endothelial cells have obvious pathological changes in many kinds of childhood kidney diseases, and have specific meanings. Among them, the proliferation of endothelial cells in intracapillary proliferative glomerulonephritis mediated by immune complex is of great significance for treatment and prognosis. Relevant domestic and foreign studies are summarized as follows.

achalasia (AC), also known as cardia spasm and megaesophagus, is mainly characterized by lack of esophageal peristalsis, high pressure in the lower esophageal sphincter (LES) and weakened relaxation response to swallowing movements. Willis first reported the disease in 1674^[1]and described as "food obstruction of the esophagus". Hurst first proposed the concept of AC in 1929^[1]。 This disease is rare in children, and the incidence rate is lower under 5 years old, and it is more common in boys. According to foreign data, it is about 0.18/100,000 per year among adolescents younger than 16^[2]And the incidence rate has a gradual increasing trend with age^[2,3,4]。 From 1990 to 2007, Tangdu Hospital of the Fourth Military Medical University treated 80 patients with AC, including 16 patients aged 1 to 14 years, accounting for 20%. The main clinical manifestations are dysphagia, postprandial rejection and some atypical symptoms, such as recurrent lung infection, cough at night, aspiration, feeding difficulty, growth retardation, etc^[3,4,5]Is prone to clinical misdiagnosis. At present, the treatment of this disease aims to reduce the pressure of LES and relieve the symptoms of patients, and its methods include drug therapy, endoscopic therapy and surgical therapy. The research progress on the etiology, clinical manifestations, diagnosis and treatment of AC in children is reviewed as follows.

bronchial asthma (asthma) is one of the most common chronic diseases in the world today. With the acceleration of industrial development and urbanization in China, the role of environmental factors in the pathogenesis of asthma has been paid more and more attention. In recent years, the frequent occurrence of haze weather in some cities in China has attracted widespread attention, and fine particulate matter with aerodynamic diameter ≤2.5 μ m (PM_2.5) is the main culprit of the haze weather. PM_2.5It has certain damage to all systems of the body, especially to the respiratory system, and is related to the occurrence of lung diseases such as lung cancer, chronic obstructive pulmonary disease and asthma in adults. The lung development of infants and young children is transferred from the intrauterine stage to the childhood stage, and the immune system and respiratory system are relatively immature._2.5The sensitivity of environmental pollutants increases. However, children generally have more outdoor activities than adults, and their total amount of outdoor air inhaled per kilogram of body weight is about 50% more than that of adults. Compared with adults, children may face more PM_2.5expose^[1], PM_2.5Special attention should be paid to the effects on children, especially childhood asthma. Now to PM_2.5The research progress on the relationship with childhood asthma is reviewed.

The objects of pediatric research are quite special. From the perspective of ethics, its research objects belong to vulnerable groups. Therefore, it is more challenging to carry out research in pediatrics. Problems such as mental health, behavior, cognition, medical experience, communication, barriers to the implementation of certain measures and facilitating factors in the field of pediatrics are difficult to complete using common quantitative research methods, and methods of applying qualitative research can be considered.