2018年 · 第56卷第03期

glucocorticoids (GC) have been tested for more than 70 years since their clinical application in 1940s. Besides being used as an alternative treatment for endocrine diseases such as adrenal dysfunction, their powerful anti-inflammatory, anti-allergic and immunomodulatory pharmacological effects make them widely used in inflammatory, allergic, immune and neoplastic diseases.

primary immunodeficiency (PID) is a group of clinical syndromes in which gene mutation leads to defects in immune organs, immune cells and immune active molecules, which ultimately leads to abnormal immune function. In 2015, the latest classification standard of the PID Expert Committee of the International Federation of Immunological Societies (IUIS) divided PIDs into 9 categories, involving more than 290 PIDs caused by more than 300 gene mutations^[1]In the past two years, new PID pathogenic genes have been discovered one after another, and it is estimated that more than 500 types of PID diseases have reached. PID seriously threatens children's health, and it is urgent to comprehensively improve the level of PID diagnosis and treatment in China. 2011 Yang Xiqiang and Zhao Xiaodong^[2]The clinical research on PID in China is divided into two stages: enlightenment and development, and the important direction of PID development in the next 5~10 years is defined, including standardizing the clinical diagnosis path of PID, improving the construction of PID-related immunology and molecular genetics laboratories, carrying out scientific research and discovering new PID, etc. 2014 Xiaodong Zhao and Yuan Ding^[3]The key technologies and tasks for clinical prevention and treatment of PID in China in the next 3~5 years were clearly put forward, and the research on "Key Technologies for Prevention and Treatment of Primary Immunodeficiency Diseases", a special scientific research project for national public welfare industries, was presided over. Three years since the project was launched, the reference system of PID early identification clues has been established^[4]It has improved the construction of national regional PID diagnosis and treatment centers and molecular diagnosis experimental platforms, and formulated a series of industry norms such as PID antibacterial drug prevention and treatment, vaccination guidance, etc., which has greatly improved pediatricians' cognitive ability of PID and marked the clinical research of PID in my country. Research has successfully entered a stage of rapid and mature development.

glucocorticoids (GC) have a wide range of anti-inflammatory and immunosuppressive effects. They are the basic therapeutic drugs for rheumatic diseases. They are widely used in the treatment of rheumatic diseases, and generally need a long time of application. Long-term application of GC will lead to a series of adverse reactions, including recurrent infection, hypertension, diabetes, osteoporosis, glaucoma or cataract, especially affecting the growth and development of children, and seriously reducing the quality of life of children. Therefore, giving full play to the therapeutic effect of GC and minimizing its adverse reactions has always been the goal pursued by pediatric rheumatologists. In view of this, the Children's Drug Committee of the Pediatric Branch of the Chinese Medical Association, the Immunology Group of the Pediatric Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Journal of Pediatrics initiated the formulation of an expert consensus on the application of GC in the treatment of rheumatic diseases.

In the past 20 years, worldwide attention to autism spectrum disorder (ASD), a neurodevelopmental disorder with social interaction disorders as the core defect, has increased significantly, and more and more children with ASD have been diagnosed. People have fully realized the importance of early diagnosis and early intervention, and also recognized the difficulty and complexity of clinical diagnosis and intervention treatment of ASD. Most children have been found to have various other developmental disorders, nutritional problems, physical diseases, psychological behavioral problems and even mental disorders before, at the same time or after the diagnosis of ASD, and most children have more than two problems^[1]。 These co-morbidities not only increase the difficulty of intervention, treatment, education and feeding, but also have a significant impact on the prognosis of children.

Male, 9 years old, went to Guangzhou Women's and Children's Medical Center for "foamy urine found for 1 week". The child had no obvious trigger to develop foamy urine, no macroscopic hematuria, no peculiar smell, no frequent urination, urgency, painful urination, and no edema before 1 week. Urinary routine in other hospitals showed: urine specific gravity 1.014, urine protein (+ +), and no abnormalities were found. Metabolic biochemistry showed that alanine aminotransferase was 17 U/L, aspartate aminotransferase was 54 U/L, albumin was 44.2 g/L, and total cholesterol was 5.96 mmol/L. Then he was transferred to our hospital for outpatient treatment. Metabolism and biochemistry showed: alanine aminotransferase 18 U/L, aspartate aminotransferase 48 U/L, albumin 45.5 g/L, urea nitrogen 3.50 mmol/L, creatinine 57 μ mol/L, uric acid 256 μ mol/L. Electrolytes are normal. Anti-streptolysin "O" 47 IU/ml. Urinary routine showed: specific gravity 1.024, protein (+ +), red blood cells 0/μ L, white blood cells 0.66/μ L. The levels of immunoglobulins A, G, M and E were normal, the levels of complement C3 and C4 were normal, and ceruloplasmin was not abnormal. B-mode ultrasound of urinary tract showed that the morphology of both kidneys was normal, the left kidney was 65 mm ×35 mm, the right kidney was 59 mm ×24 mm, and no cysts were seen. Then it was admitted to our department for further diagnosis and treatment with "proteinuria cause check". Since the onset of the disease, the spirit and appetite of the child are good, and the urine is as mentioned above, and the stool is not abnormal.

An 8-year-old male was admitted to the Pediatric Intensive Care Unit (PICU) of Xiangya Hospital of Central South University in July 2017 due to "fever for 24 days, convulsions and disorder of consciousness for 21 days". The child developed fever and convulsions without obvious trigger 24 days ago, manifested as strabismus in both eyes, skewed mouth corners, and twitching of limbs. Several attacks lasted for about 10 minutes each time, and then developed disturbance of consciousness. After treatment in the local hospital, the condition still worsened. Transfer to provincial hospital to improve cerebrospinal fluid examination, which showed that routine biochemistry, staining, culture and autoimmune encephalitis were negative for multiple antibodies and virus antibodies; There was no abnormality in the enhancement of skull MRI plain scan; EEG showed slowdown of background activity. Considering the diagnosis of "severe encephalitis, persistence of convulsions", antiviral, combined anti-infection, gamma globulin, methylprednisolone to regulate immunity, plasma exchange and anticonvulsant treatment with midazolam, phenobarbital, propofol, topiramate and clonazepam, the child's condition did not improve, so he was transferred to our hospital.

Female, 4 years and 4 months old, Yi nationality. He was admitted to the Second Hospital of West China of Sichuan University in February 2017 because of "bloody feces for more than 9 months". More than 9 months before admission, the child developed diarrhea, which lasted for 5 to 6 days. After oral administration of antidiarrheal drugs (details unknown), the feces gradually dried out, and then the formed feces with blood and mucus attached to the surface were discharged. Occasional periumbilical pain was unknown, and there was no fever, cough, vomiting, etc. After treatment in the local hospital and Liangshan First People's Hospital for a total of 25 days (details unknown), there was no more bloody stools. After 1 month, the bloody stool is discharged again, bright red or dark red, sometimes thin and sometimes dry, 5 to 6 times/d when thin, and the blood volume is slightly more; When dry 2~3 times/d, the blood volume is slightly less; Occasionally, it is urgent and then heavy. One month ago, colonoscopy in West China Hospital showed "colorectal erosion and intestinal parasitic infection", and then went to Liangshan First People's Hospital. Colonoscopy biopsy histopathology showed a small amount of mucus and several inflammatory cells, and was diagnosed with "chronic diarrhea and blood in stool to be diagnosed; intestinal parasitic disease? Inflammatory bowel disease?", and was treated with "levamisole deworming". Two white round long dead worms, about 12 cm long and 0.3 cm in diameter, were discharged with feces 20 days ago. Four days ago, bright red morning urine appeared once, the amount was moderate, without urinary tract irritation symptoms, and the urine color was normal later. After treatment, the child's bloody stool improved slightly and then he was admitted to our hospital. Since the disease, the child's spirit, diet and sleep are normal, occasionally complaining of perianal itching, and the weight loss is about 0.5 kg. In the past, he was in good health, and he always liked to go to the ground with his feet. He denied the history of eating raw beef, mutton, shrimp and crab and drinking raw water, and denied the history of allergies and trauma.

Male, 6 years old, went to Peking University First Hospital in March 2016 because of "abnormal hand posture for 3 years and abnormal gait for 1 and a half years". Three years ago, the child gradually discovered abnormal left hand posture without obvious inducement, which showed that the left hand ring finger could not be straightened, and the right hand was weak in writing, which did not affect eating with chopsticks. After 1 1/2 years, it gradually progressed to restricted movement of finger joints, metacarpophalangeal joints and wrists, affected operations such as writing and eating, dragging of the left lower limb, walking claudication, and continued progressive aggravation. Urination and defecation are normal. Physical examination: Conscious and fluent in language. Cranial nerve examination showed no abnormalities. The knuckles of both hands were flexed, the wrists were drooped, the muscle strength of both upper limbs was grade IV at the proximal end and grade III at the distal end, more obviously on the left side, and the thenar muscles of both upper limbs were obviously atrophied. The proximal muscle strength of both lower limbs was grade IV, the distal left lower limb was grade III, and the distal right lower limb was grade IV. The tendon reflexes of both upper and lower limbs were not drawn out, and the muscle tone of the limbs was acceptable. Negative pathological signs, unstable and accurate finger-nose test, inability to walk in a straight line, dragging gait. There were no abnormalities in the sensory system examination. Laboratory tests: liver and kidney function, myocardial enzymes, blood lipids, blood ammonia, lactic acid and homocysteine were normal, and blood and urine metabolism screening were normal. Cerebrospinal fluid routine, biochemistry normal, blood and cerebrospinal fluid oligoclonal zone, ganglioside profile antibody negative. There were no abnormalities in hand orthographic radiography, brain CT, cervical, thoracic and lumbar spine and cranial magnetic resonance imaging (MRI). Genetic examination of peripheral neuropathy and spastic paraplegia showed no significant mutations. Electromyography examinations performed in other hospitals in December 2014 and June 2015 respectively showed neurogenic damage in both upper limbs. Since August 2015, four electromyography examinations performed in Peking University First Hospital showed neurogenic damage, slowed down sensory nerve conduction velocity (SCV), decreased sensory nerve action potential (SNAP) amplitude, slowed down nerve motor conduction velocity (MCV) of upper limb motor nerve (left median nerve and ulnar nerve), decreased compound muscle action potential (CMAP) amplitude, segmented stimulation, and conduction block, with a decrease of 85% ~86%; The MCV of lower limb motor nerve slowed down gradually, and the CMAP amplitude of left common peroneal nerve decreased. Treatment and follow-up: Intravenous immunoglobulin (IVIG) was given twice in April 2016 and May 2016, respectively, at a dose of 2 g/ (kg·d) ×2 d. The symptoms still progressed slowly, and the electrophysiological examination did not improve significantly. In August 2017, methylprednisolone 20 mg/ (kg·d) ×3 d pulse therapy was started, repeated every 4 d for 3 rounds, and then changed to prednisolone tablets 2 mg/ (kg·d) orally, and the dose was gradually reduced for 4 to 6 weeks. The drug has been discontinued for 2 months, and the child's limb weakness has not progressed yet. During this period, it was planned to improve sensory nerve biopsy, but the family failed to agree.

The 11-year-old male was admitted to the Department of Rheumatology and Immunology of Tianjin Children's Hospital for the first time in April 2017 mainly because of "8 months of reduced language and activity, limb weakness with rash for half a year". Reduced speech and unwillingness to move 8 months before admission; Six months before admission, I developed limb pain, weakness, slow walking, accompanied by decreased appetite and occasional difficulty in swallowing, and lost 15 kg in weight in six months. Fever occurred on the day of admission, with a maximum body temperature of 38.0 ℃. Hair loss has been obvious in the past 2 months. There was no cough, no oral ulcer, no joint swelling during the course of the disease. Since the onset of the disease, mental poverty, intermittent irritability, poor appetite. Past physical fitness; Personal history is not special; Family history of connective tissue disorders denied.

juvenile idiopathic arthritis (JIA) is the most common chronic non-suppurative arthritis in childhood. At present, it is believed that it is the joint action of genes and environmental factors, and has complex genetic characteristics. In the study of siblings of JIA, it was found that the characteristics of the disease were highly consistent with the disease process. Among the children with monozygotic twins, 25% ~40% of the children with twins would develop the same disease phenotype^[1]。 Further epidemiological studies on JIA families showed that the incidence rate of JIA was 15~30 times that of the general population^[2]。 All the above studies indicate that JIA has susceptibility genes. According to the 2001 classification criteria of the International League of Rheumatology Association (ILAR), JIA was classified into seven subtypes^[3]。 Systemic JIA (So-JIA) is a subtype that potentially endangers children's lives, and its immune mechanism is currently the most controversial. In recent years, there has been a growing view that So-JIA is an autoinflammatory disease and should be independent of JIA^[4]。 With the continuous development of gene technology, gene research methods are more mature. This paper reviews the research progress of So-JIA genetic susceptibility genes, aiming at re-understanding the pathogenesis of So-JIA from the genetic level.

Merosin protein-deficient congenital muscular dystrophy, also known as congenital muscular dystrophy, type 1A (MDC1A), is the most common subtype of congenital muscular dystrophy in China^[1]。 MDC1A is associated with a defect in the α 2 chain (laminin α 2, laminin-α 2, also known as merosin), one of the three subunits of laminin 2 (Laminin-211). A deficiency of this protein can cause disruption of the junction between the cytoskeleton and the extracellular matrix^[2,3]。 In 1995, it was discovered that mutations in the LAMA2 gene encoding laminin-α 2 can lead to merosin protein-deficient congenital muscular dystrophy^[3]The related research progress in recent years is summarized as follows.

Warfarin, a derivative of dicoumarin, is currently the most widely used oral anticoagulant^[1]。 Coagulation factors II, VII, IX, X containing glutamic acid residues in warfarin, as well as protein C and protein S, become active only after being carboxylated by γ-glutamyl carboxylase (GGCX), and then a series of cascade reactions occur to cause blood coagulation. Reduced vitamin K is an essential cofactor for GGCX, and vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces oxidized vitamin K to reduced vitamin K. Warfarin inhibits the activity of VKORC1, prevents the production of reduced vitamin K, and blocks the activation of the above-mentioned coagulation factors, thus exerting anticoagulant effect. However, its treatment window is narrow, individual differences are large, and adverse reactions are prone to occur. A large number of studies have shown that the difference of average daily warfarin dose between individuals is closely related to drug gene polymorphism^[1]。 Warfarin drug genes are divided into two categories: (1) warfarin targets and metabolism-related genes, such as VKORC1 and cytochrome P450 enzyme 2C9 (CYP2C9); (2) Genes related to the metabolic cycle of vitamin K in the body, such as GGCX, cytochrome P450 enzyme 4F2 (CYP4F2), microsomal epoxide hydrolase (EPHX1), apolipoprotein E (APOE), etc.^[2]。 In the field of pediatrics, diseases or states such as Kawasaki disease and giant coronary aneurysm formation^[3]The use of warfarin anticoagulant therapy after Fontan surgery, prosthetic heart valve replacement and deep vein thrombosis has gradually become the standard treatment plan. However, warfarin has not been used in pediatrics for a long time, and clinicians have limited experience in using warfarin, and evidence-based evidence is still lacking. Multiple studies have shown that the International Association for Warfarin Pharmacogenetics (IWPC) dose prediction formula based on warfarin drug gene polymorphisms overestimates childhood warfarin doses, suggesting the specificity of childhood pharmacogenetics. The effect of gene polymorphism on warfarin dose in children is reviewed as follows^[4]。

The 2018 Joint Meeting of Editors-in-Chief of Chinese Journal of Pediatrics was successfully held in Hangzhou on January 13, 2018. Professor Yang Xiqiang, Chairman of the Academic Steering Committee, and Professor Hu Yiji, a member of the Committee; Honorary Editor-in-Chief Professor Gui Yonghao, Editor-in-Chief Professor Du Junbao, Deputy Editor-in-Chief Professor Du Lizhong, Feng Zhichun, Hong Jianguo, Huang Guoying, Li Tingyu, Luo Xiaoping, Mao Meng, Qian Yuan, Song Hongmei, Wang Tianyou and Zhao Zhengyan; Professors Ding Jie, Gong Sitang and Zhao Xiaodong, Assistant Editor-in-Chief, attended the meeting.

Case report forms (CRFs) or questionnaires are commonly used information gathering tools in clinical research. Some researchers often wonder during the design stage, whether the CRF or questionnaire designed by themselves needs to be examined for reliability and validity before using it? Before raising this question, we should first understand the difference and connection between CRF and scale.