2013年 · 第51卷第07期

Dr. Zhang Yaming (225300 Department of Pediatrics, Taizhou People's Hospital, Jiangsu Province) asked:

After more than two years of efforts from 2009 to 2010, the Nephrology Group of Pediatrics Branch of Chinese Medical Association formulated seven evidence-based guidelines for the diagnosis and treatment of common kidney diseases in children, which were successively published in the Chinese Journal of Pediatrics^{[1,2,3,4,5,6,7]}。 While working hard and summarizing our achievements, we deeply feel that the treatment of children's kidney disease in China is still facing great challenges. Although we have a large patient base, accumulated rich practical experience, and are constantly using various media or opportunities (such as academic journals, academic conferences, continuing medical education lectures, etc.) to widely disseminate existing treatment experiences and experiences, how to find "clinical evidence-supported, reliable diagnostic methods and more effective treatment options"^[8]There are still deficiencies in aspects. There are still many shortcomings in applying the concept of evidence-based medicine, a new medical model that has developed rapidly in the international clinical field in recent years, to promote the development of clinical therapeutics faster and optimize our treatment work. In the process of formulating the evidence-based diagnosis and treatment guidelines for common childhood kidney diseases, we found that almost all the existing "clinical evidence" comes from foreign literature reports, while very few research results on clinical treatment in China can be recommended as "evidence" into the guidelines. There are many related research reports in China, but many studies are biased and cannot be widely accepted and popularized. For example, most studies come from a single center, which cannot overcome the bias caused by the source of cases and doctors' medical habits; Some clinical studies summarize and analyze a large number of cases, but the variation between cases is large and the comparability is poor; Or treatment studies have no control, insufficient follow-up, and it is difficult to evaluate the efficacy.

On August 20, 2011, the Clinical Pharmacology Group of Pediatrics Branch of Chinese Medical Association was born in Beijing, officially becoming one of the 14 professional groups of Pediatrics Branch, which is a milestone in the history of pediatric clinical pharmacology development in China. As Professor Zuo Qihua, the famous founder of pediatric neurology, said in his congratulatory letter: "This is an authoritative academic organization that is in line with international standards. After more than 30 years of efforts, it has succeeded. It is a real big event. It is a big event for the pediatric branch of Chinese Medical Association, and a big event for pharmacology. It is a big event worth celebrating."

Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood, mainly small vasculitis as a systemic syndrome with pathological changes. The clinical manifestation of HSP is non-thrombocytopenic palpable cutaneous purpura with or without abdominal pain, gastrointestinal bleeding, joint pain, kidney damage and other symptoms. Most are benign self-limiting processes, but severe gastrointestinal tract, kidney and other organ damage can also occur^[1,2]。 At present, the pathogenesis of HSP is still unclear, and there is still a lack of unified treatment plan and standardized follow-up. In order to standardize the clinical diagnosis and treatment of HSP in children, in February 2012, the Immunology Group of Pediatrics Branch of Chinese Medical Association held an expert symposium on the diagnosis and treatment of HSP in children in Changsha, Hunan Province, and decided to formulate this diagnosis and treatment recommendation according to the principle of evidence-based methodology. In September and October 2012, the first draft of the guidelines were discussed at the 17th National Pediatrics Conference of Chinese Medical Association and the National Pediatric Immunity Conference of Chinese Medical Association, respectively. This diagnosis and treatment proposal collects original clinical studies from adults and pediatrics, comprehensive data from various databases at home and abroad, diagnosis and treatment guidelines, expert consensus and other literature materials to the maximum extent, analyzes and summarizes, and forms diagnosis and treatment suggestions on this basis. This recommendation is applicable to pediatricians who have some foundation or experience in the diagnosis and treatment of pediatric diseases. When targeting specific children, this guideline is not a diagnosis and treatment standard that clinicians must implement. Clinicians should fully understand the best clinical evidence and existing medical resources of this disease, and adopt appropriate diagnosis and treatment plans.

Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood. Although the clinical symptoms are mild and self-healing, severe cases may have gastrointestinal damage symptoms (abdominal pain, intestinal bleeding, intestinal obstruction, intestinal perforation and intussusception), kidney damage and other organs (brain, lung and other vasculitis) damage, and even life-threatening, so clinicians need to adopt appropriate diagnosis and treatment plans in time. At present, there is still a lack of unified treatment plan and follow-up standard for HSP at home and abroad, and there are many controversies about the prevention and treatment measures of Henoch-Schönlein purpura nephritis (HSPN). To this end, we collected original clinical studies from adults and pediatrics, comprehensive data from various databases at home and abroad, diagnosis and treatment guidelines, expert consensus and other literature materials, and formulated "Evidence-based Diagnosis and Treatment Recommendations for Children with Henoch-Schonlein Purpura" (hereinafter referred to as "Recommendations") according to the principle of evidence-based medicine. In September and October 2012, the first draft of the recommendations was discussed and revised at the 17th National Pediatrics Academic Conference of Chinese Medical Association and the National Pediatric Immunity Academic Conference of Chinese Medical Association respectively. Since the Nephrology Group of Pediatrics Branch of Chinese Medical Association has formulated the diagnosis and treatment guidelines for purpura nephritis, this recommendation seldom involves purpura nephritis. Now, the relevant issues of the recommendations for the diagnosis and treatment of HSP in children are interpreted as follows:

Child, 11 years old, Mongolian. See a doctor for "intermittent chest pain for more than 1 year". One year ago, the child felt pain in the precordial area after strenuous activity, which was relieved after 5 to 6 minutes of rest. After that, the above symptoms occurred intermittently. When the child was 5 years old, he was diagnosed with multiple symmetrical xanthomas of joints in the whole body, and the serum total cholesterol was 21 mmol/L. Both the child's grandmother and parents had hypercholesterolemia, the parents were cousins, and the mother had blepharoid xanthoma. Physical examination: A systolic grade 3/6 murmur was heard in the second auscultation area of the aortic valve, and it was conducted to the neck. Multiple xanthomas, with a diameter of 1.0~3.0 cm, can be seen in eyelids, knuckles, elbow joints and knee joints. Laboratory tests: serum low density lipoprotein (LDL) 15.93 mmol/L, triglycerides 3.25 mmol/L, total cholesterol 17.60 mmol/L. The electrocardiogram showed ST segment depression of more than 0.5 mV in leads V1~ V6 after activity, and T wave was inverted. Echocardiography showed that the wall of the aortic annulus and the initial end of the ascending aorta was thickened, strong echoic plaque was seen on the wall, and the lumen was narrowed. The narrowest part is located at the sinus junction, where the cross-sectional area is 0.84 cm²。 The aortic valve leaflet is thickened, localized calcification, and limited opening. The wall of the left coronary artery was not smooth, and the blood flow velocity was accelerated, with a peak velocity of about 1.9 m/s. Bilateral carotid intima thickened, plaque formed, and lumen stenosis (Figure 1、Figure 2)。 Cardiac catheterization measured the aortic valve-ascending aorta pressure step difference of 70 mm Hg (1 mm Hg =0.133 kPa), and coronary angiography showed 60% to 70% stenosis at the opening of the left coronary artery (Figure 3、Figure 4), aortomography showed moderate to severe regurgitation of the aortic valve. The clinical diagnosis was familial hypercholesterolemia (FH), aortic valve and supravalvular stenosis, aortic insufficiency, and coronary atherosclerotic heart disease (CHD).

The 5-year-old child was admitted to the hospital in November 2012 due to "intermittent abdominal pain with the finding of increased platelets for 10 days". The child developed paroxysmal abdominal pain without obvious trigger 10 days before admission, mainly around the umbilicus. No nausea, vomiting, no fever, runny nose, no diarrhea, constipation. No obvious tendency to mucosal bleeding was observed. Blood test routine in local hospital: white blood cells 27.29×10⁹/L, red blood cells 5.35×10¹²/L, hemoglobin 140 g/L, platelets 1905×10⁹/L, C-reactive protein (CRP)<8 mg/L. Given intravenous anti-infective drugs, the abdominal pain was slightly relieved, and there was no obvious change in the blood routine. After that, the child still had intermittent abdominal pain attacks, so he went to our hospital for further treatment.

Example 1The child, male, 8 years old and 10 months old, was admitted to hospital due to "fever and cough for 2 weeks". The child developed fever and paroxysmal cough without phlegm 2 weeks before admission without obvious inducement, with a fever peak of 40℃ and chills. The chest X-ray of the local hospital showed "upper left pneumonia". He was given intravenous infusion of cephalosporin antibiotics for 5 days, but there was no improvement, so he was transferred to our hospital. During the course of the disease, there were no bruises, night sweats and weight loss, vomiting and abdominal pain, rash and joint swelling and pain. Prior health, no history of drug or food allergies. G2P2, delivered naturally at term. He denied family medical history, his parents were not married by close relatives, and he had one sister, both of whom were in good health. Physical examination: Body temperature 38.5 ℃, heart rate 102 beats/min, 27 breaths/min, body weight 14 kg. Clearness, poor spirit, no pale edema, rash, and superficial lymph nodes of the whole body. The lips are not cyanotic, the breathing sounds of both lungs are thick, and the left side is slightly lower, not as good as rales. Heart sounds are powerful, rhythmic, and no murmur. The abdomen is soft, without tenderness, and the liver and spleen are not reached under the costs. Freedom of movement of limbs, no swelling of joints, no pestle-like digits and no positive signs of nervous system. Routine blood test at admission: white blood cells 11.45×10⁹/L, neutrophil classification 0.573, hemoglobin 119 g/L, platelets 103×10⁹/L, erythrocyte sedimentation rate 87 mm/1h, CRP 59 mg/L, serum mycoplasma pneumoniae (MP) IgM titer>1:160 by ELISA, sputum fluorescence quantitative PCR-MP-DNA 4.5×10⁴copies/ml; Among autoantibodies, anticardiolipin antibody was positive, and there was no abnormality in the rest; There were no abnormalities in humoral immunity, cellular immunity, blood biochemistry, anti-O, coagulation routine, blood culture and sputum culture. PPD was negative, electrocardiogram and echocardiogram showed no abnormalities. Chest CT showed "large high-density shadow of left upper lung, no pleural effusion".

The child was a 13-year-old male. Seeing a doctor for "darkening skin with short stature for 10 years". When the child was 2~3 years old, his family found that his skin was darker, then progressively aggravated and rough, most obviously on the head, neck and armpit. He can walk and talk when he is more than 1 year old, and no abnormalities are found before the age of 2. However, his height is gradually shorter than that of his same age. At the same time, his appearance is also very different from that of his family. His tongue is so thick that his mouth is gradually unclear, so he is often laughed at by his classmates, and his academic performance is medium. No polydipsia, polyuria, dizziness, headache and syncope occurred. The child is the second child and the second birth, and the mother delivered at home at full term. The birth went smoothly, and her weight was not measured, "but she was fat". I usually suffer from a cold. The parents were not intimate married, physically fit, and their heights were: 170 cm and 163 cm respectively; There is a 17-year-old sister who is fit and 165 cm tall.

IgA nephropathy is one of the most common primary glomerular diseases causing chronic renal failure worldwide, especially in Asia. The long-term prognosis of IgA nephropathy is not optimistic, and the proportion of adults who enter end-stage renal disease (ESRD) after 20-30 years of follow-up can even be as high as 30%-40%. The pathogenesis of IgA nephropathy is complex, involving genetic, immune and other factors, which has not been completely understood. Among them, it has been confirmed that the abnormal glycosylation of IgA1 molecule caused by the decrease of core 1 β 3 galactosyltransferase (C1 β 3gal-T) activity is one of the important pathogenesis of IgA nephropathy. Recent basic research has found that the decrease of C1 β 3gal-T activity is closely related to the function of a protein, which is called core1 β 3-gal-T-specific molecular chaperone (Cosmc). The discovery of Cosmc provides a new research idea and direction for exploring the pathogenesis of IgA nephropathy. The following summarizes the research progress of the pathogenic mechanism of Cosmc in IgA nephropathy.

Congenital heart disease refers to the structural abnormality of the heart and large blood vessels. The incidence rate in the world is 0.8% ~1%, without obvious regional and ethnic specificity. It ranks first in the incidence of congenital malformations. Because of its high incidence rate and serious consequences, it has been widely paid attention to by people. At present, congenital heart disease is believed to be a polygenic disease affected by environment and genetics, but its pathogenesis and how to interact are still unclear.

It is generally believed that Mycoplasma pneumoniae (MP) causes disease mainly through adhesion to the host surface, cytotoxicity, molecular mimicry and antigenic variation^[1,2]But its exact pathogenic mechanism remains to be elucidated. Unlike other bacteria, no virulence factors directly related to the pathogenesis of MP have been found so far. 2005 Kannan et al.^[3]The discovery of community-acquired respiratory distress syndrome toxin (CARDS TX) in MP fills this gap and provides new ideas for further explaining the pathogenesis of MP. The research progress of CARDS TX is reviewed.