2015年 · 第53卷第11期

myelodysplastic syndromes (MDS) include a group of malignant myeloid clonal diseases, which originate from hematopoietic stem and progenitor cells, and are clinically manifested as peripheral blood cytopenia, abnormal development of one or more hematopoietic cells in the bone marrow, and easily develop into acute myelogenous leukemia (AML). MDS in children is very rare, with an annual incidence rate of approximately 1.8/1 million^[1,2], accounting for less than 5% of hematopoietic tumors in children. Because of the huge differences in clinical biological characteristics and treatment strategies between pediatric MDS and adult MDS, and the poor prognosis, related research has always been one of the research hotspots in pediatric hematology.

myelodysplastic syndrome (MDS) is a group of malignant myeloid clonal diseases originating from hematopoietic stem and progenitor cells. It is characterized by peripheral blood cytopenia, abnormal development of one or more hematopoietic cells in bone marrow, and easy evolution to acute myeloid leukemia (AML). At present, the clinical diagnosis and treatment of MDS is still one of the difficulties in the international hematology field^[1,2,3]。 Although MDS is one of the most common hematological malignant diseases in the elderly (median age 70 years), it is very rare in children. In recent years, international epidemiological data show that the annual incidence of MDS in children is only about 1.8/1 million, accounting for about 5% of malignant hematological tumors in childhood. The average age of onset is about 6.8 years, of which the average age of advanced MDS is about 10.7 years, and the ratio of male to female is 2:1^[4,5]。 The diagnosis of MDS in children is difficult and the prognosis is poor, so it should be of high clinical concern. Studies have shown that there are huge differences between children and adults in MDS, regardless of incidence, etiology or bone marrow morphology, cellular and molecular genetics, and even treatment strategies^[3]。 The same as adults is "hematopoietic dysfunction", which is also the most basic characteristic of MDS in children. In 2001, the World Health Organization (WHO) expert group clearly proposed that MDS is a disease originating from clonal hematopoietic stem and progenitor cell dysplasia (dysplasia), and classified MDS as "hematopoietic neoplastic diseases". In 2005, the International Children's Cancer Organization also classified children's myelodysplasia and myeloproliferative diseases as tumor diseases. In the 2008 WHO-MDS diagnostic classification revision, relatively independent diagnostic classification criteria have been recommended for pediatric MDS^[1,2,3]。

An 8-year-old male was admitted to hospital for "intermittent skin, mucosa and joint bleeding for 5 years". The 2-year-old and 2-month-old child bled continuously after head bump, and it improved after suture to stop the bleeding. After that, intermittent skin and joint soft tissue bleeding occurred, which was manifested as a mass at the bleeding site, which was hard in texture, and intermittent epistaxis was not paid attention to. Recurrent epistaxis occurred again at 7 years and 8 months without obvious trigger, and it was gradually unable to stop itself. He was seen at the local hospital at the age of 8, considered to be hemophilia, and was given a transfusion of prothrombin complex once. Two days later, the child had bleeding in the right knee and could not walk, so he was seen in the Department of Pediatric Hematology of our hospital. The child is the second child and the second birth, full-term cesarean section, no history of hypoxia and asphyxia, regular prenatal examination during pregnancy, denial of history of hypertension and diabetes during pregnancy, denial of history of contact with infectious diseases such as hepatitis and tuberculosis, and has an older brother who is in good health. Family history of similar disease is denied.

A male, 2 years old and 1 month old, was admitted to hospital because of "foamy urine found for more than half a month". About 20 days before admission, the child was found to have more foamy urine, no fever, no frequent urination, urgency, painful urination, and no macroscopic hematuria, which was not paid attention by the parents. Because the child's symptoms did not alleviate, he recently went to the local hospital to check the urine routine: "protein (+), white blood cells (+ +)", so he went to our hospital for treatment, and the outpatient urine red blood cell morphology examination showed "urine protein (+ + +), white blood cells 30.4×10⁶The child had no fever, rash, cough, vomiting and diarrhea, no edema, food, appetite and sleep, no polydipsia, polyuria, normal urine output, more foam, and no abnormal appearance of stool.

The male child, born 30 minutes, was admitted to Guangdong Maternal and Child Health Hospital in 2014 because of "the discovery of a lung mass for 1 month". Prenatal B-ultrasound examination of her mother at 30 weeks of pregnancy revealed an oval mass of 0.8 cm ×1.0 cm in size in the left lung of the child with clear borders (Figure 1)。 Reexamination of B-ultrasound at 34 weeks of pregnancy showed no mass. The child is the second and first birth of her mother, gestational age 34^＋6Weeks after cesarean section, the amniotic fluid was clear at birth, the birth weight was 2.57 kg, the postnatal Apgar's score was 9, 10 and 10 points at 1, 5 and 10 min, respectively, and there was no discomfort such as dyspnea after birth. Physical examination at admission: vital signs were stable, response was acceptable, respiratory movement was symmetrical, no three concave signs were seen, respiratory sounds in both lungs were clear, and dry and wet rales were not heard. The heart rhythm was uniform, and no pathological murmur was heard in the auscultation area of each valve. The abdomen is soft and not distended, the liver and spleen are not palpable under the ribs, and the intestinal sounds are about 4 times/min. Chest + abdomen X-ray after admission (Figure 2) shows: dense shadow of left lower lung, not excluded occupying space; Neonatal pneumonia. Chest CT (Figure 3) shows that a high-density occupancy of 4.2 cm ×2.7 cm can be seen in the lower lobe of the left lung, which is quasi-circular with blurred boundary, and bronchial inflation sign can be seen in it. The enhancement scan shows obvious uneven enhancement, and the enhancement law is similar to that of the liver. The blood supply vessels come from pulmonary arteries and pulmonary veins; Multiple patchy blurred shadows were seen in the remaining lung fields. Fiberoptic bronchoscopy reports: inflammation of the endobronchial lining; Left lower lobe airway stenosis (external pressure). Admission diagnosis: (1) neonatal pneumonia, (2) left lower lung space occupation (unknown nature), (3) premature infant. After admission, he was given anti-infective and symptomatic supportive treatment. After his condition was stable, he underwent left lower lobectomy under tracheal general anesthesia. During the operation, the left upper lobe tissue was intact in appearance, and a mass was seen in the parenchyma of the left lower lung, which was not inflated, gray-white in color, with unclear boundary with lung tissue and no adhesion with the surrounding pleura. No abnormal blood supply was observed; Tough texture. Postoperative pathological examination (Figure 4) Considered as congenital peribronchial fibroblastoma of the lung, differentiated immature cartilage tissue proliferation and myofibroid spindle cell proliferation can be seen, and the proliferated spindle cell nuclear division image is more common, reaching 5/10 high-power scope fields, and the cell proliferation is active. Immunophenotype: vimentin (+), cytokeratin (-), smooth muscle actin (SMA) (+), calmodulin binding protein (caldesmon) (-), intermyelin (-), S-100 protein (+), CD99 (+), p53 (+), CD34 (-), Ki-67 index ≈ 30%. Discharge diagnosis: (1) congenital peribronchial myofibroblastic tumor (CPMT) in left lower lung, (2) neonatal pneumonia, (3) patent ductus arteriosus, (4) patent foramen ovale, (5) premature infant.

The child was a male, 40 h, with a gestational age of 36 weeks. He was the first birth of his mother. He was admitted to the Department of Neonatology of Chenzhou First People's Hospital affiliated to South China University in March 2015 because the child "twitched his limbs and did not suck for 28 h". The mother of the child had "drug abuse history (methamphetamine)" in the early, middle and third trimester of pregnancy. The child was born by cesarean section due to "premature rupture of membranes for 4 h", and the history of postnatal asphyxia and rescue was denied. The birth weight was 2 400 g, and the Alpha score was 8, 10 and 10 points at 1, 5 and 10 minutes, respectively. The child had limbs twitching 12 h after birth, especially the lower limbs. The twitching was obvious after being stimulated by sound and light, and it could be relieved after being quiet, but it had frequent attacks, accompanied by non-sucking, poor response, no eyes turning up, no foaming at the mouth and cyanosis, etc. He came to our hospital 40 h after birth and was hospitalized.

A 3-year-old male was admitted to the Pediatric Intensive Care Unit (PICU) of Peking University First Hospital on December 25, 2011 due to "repeated fever, splenomegaly for 9 months and oliguria for 3 days". Within 9 months before admission, the child had 5 times of high fever without obvious trigger and no obvious accompanying symptoms; Spleen enlargement, pancytopenia, hypertriglyceridemia persisted during the visit to other hospitals, and reticular phagocytes were seen in bone marrow smears; Diagnosis of hemophagocytic lymphohistiocytosis (HLH); In the past, immunotherapy and/or chemotherapy were not used for onset of disease. After anti-infection and symptomatic treatment, the body temperature dropped to normal, the spleen shrank, and the blood routine returned to normal. During the treatment, the kidney function was always normal. High fever reappeared 1 week ago, oliguria (300 ml/d) occurred during treatment in an outside hospital 3 days ago, and blood creatinine was found to be elevated 1 day ago and transferred to our hospital. The child was previously in good health, the first birth, the first birth, the full-term natural delivery, and there was no history of distress and asphyxia. The parents were not intimate married, and the family history of related diseases was denied.

A 5-month-old male was admitted to hospital due to repeated cough for 2 months, fever and shortness of breath for 16 days. Two months before admission, the child developed a cough without obvious trigger, which was paroxysmal cough with phlegm that was difficult to cough up, and no accompanying manifestations such as fever, rash, wheezing, choking, etc. He was hospitalized in the local hospital twice and diagnosed as "bronchitis and bronchopneumonia". Each time, he was treated with intravenous drip of cefotiam and methylprednisolone for more than 1 week and was discharged. 16 days before admission, the child had cough again, phlegm in the throat was more significant, accompanied by fever, asthma, shortness of breath, the highest body temperature was 38 ℃, and the fever peak was once/d. He went to the local hospital again, and the blood routine showed "white blood cells 13.70×10⁹/L, neutrophils 0.537, lymphocytes 0.361, hemoglobin 96 g/L, platelets 516×10⁹/L, CRP 45.10 mg/L ", lung CT showed" pneumonia ", fiberoptic bronchoscopy showed" endobronchitis, sputum congestion in the posterior basal segment of the left lower lobe ", and the diagnosis of" severe pneumonia and tuberculosis? "He was given erythromycin, ceftriaxone, imipenem cilastatin, linezolid and other treatments successively. The child's asthma gradually improved, and his body temperature dropped to normal 1 day before admission, but he still coughed and had shortness of breath. For further diagnosis and treatment, he went to the outpatient clinic of our hospital and was admitted to the hospital with" lung lesions to be examined ". Since the onset of the disease, the child has acceptable milk and sleep, and his stool is 4-8 times a day after spontaneous birth, pasty, and his weight has not gained significantly in the past 2 months.

In recent years, with the increasing clinical application of fractional exhaled nitric oxide (FeNO) detection, especially in 2011, the American Thoracic Society released "How to Interpret FeNO Test Results in Clinical Application"^[1]After the guidelines, clinicians' understanding of the clinical value of FeNO detection has been significantly improved, which makes FeNO detection play an important role in the diagnosis and management of allergic airway diseases such as asthma^[2]。 At present, the clinical detection of FeNO is mostly performed by uniform and continuous forced exhalation, which requires good cooperation of patients. This method can only be performed in children and adults over 6 years old, and is not suitable for children under 5 years old (young). Therefore, the clinical application of FeNO in the field of pediatrics is mainly limited to older children^[3]。 It is still difficult to diagnose asthma in children under 5 years old because of the lack of detection methods suitable for this age group. The Global Asthma Initiative Committee developed the Guidelines for the Diagnosis and Management of Asthma in Children Under 5 in 2009^[4], pointing out that the diagnosis of asthma in young children mainly depends on clinical practice, and in the revised guidelines for asthma prevention and treatment in 2014, it was clearly stated that FeNO test can be used to predict whether wheezing in infants and young children develops into asthma^[5]。 Therefore, it is very important to detect FeNO in young children to clarify the relationship between infant wheezing and preschool wheezing and the occurrence and development of asthma.

The incidence of bronchopulmonary dysplasia (BPD) ranged from 12.3% to 30.0%, and the incidence of premature infants with gestational age of 22 to 28 weeks was as high as 68%^[1]It is the most common and serious complication of premature infants, which seriously threatens the survival rate and quality of life of children. BPD is closely related to lung immaturity in premature infants, and pathological changes include alveolar dysplasia, decreased alveolar number and abnormal alveolar capillary distribution^[2]。 It is difficult for early children to withdraw, the incidence of ventilator-related pneumonia increases, and long-term oxygen dependence leads to lung oxidation-antioxidation imbalance, which causes related inflammatory reactions. Infection and inflammation further aggravate BPD, forming a vicious circle, and leading to an increased risk of death. In the later stage, children are prone to severe respiratory tract infection in infant and early childhood, which affects the lung function in childhood, adolescence and even adulthood^[3,4]。 Therefore, it is called the earliest onset and longest lasting chronic lung disease^[4]。 How to better prevent and treat BPD is one of the key research topics in the international neonatal field at present. At present, most of the prevention and treatment strategies adopted are short-term symptomatic treatment. It is urgent to explore a treatment method to fundamentally repair lung injury and promote lung development. Stem cell therapy promotes lung repair and continued development at the cellular level, and is considered to be one of the best treatment options for BPD in the future. The research progress of stem cell therapy for BPD is reviewed.

Professor Hu Yamei is a famous pediatric expert in China and an academician of Chinese Academy of Engineering. He has served as the director, vice president and president of internal medicine of Beijing Children's Hospital affiliated to Capital Medical University. He has served as an honorary member of China Association for Science and Technology, a member of the Academic Degrees Committee of the State Council, a member of China Association for International Exchange, a member of the Children's Defense Committee of China Women's Federation, a vice president of Chinese Medical Association, a director of the Academic Committee of Chinese Medical Association, a chairman of the Childhood Leukemia Special Fund Committee of China Cancer Research Foundation, a deputy chairman of the editing and review committee of pediatric medical professional textbooks in medical colleges and universities, a special reviewer of the invention selection committee of the State Science and Technology Commission, an editorial board member of Chinese Journal of Pediatrics, Chinese Medical Journal, Beijing Medicine, Chinese Medical Science Yearbook and Medical Encyclopedia Pediatrics Sub-volume and other magazines and books. He is a representative of the 1st to 9th People's Congress of Beijing, the 12th and 13th National Congress of the Communist Party of China, the 7th, 8th and 9th National People's Congress. He has won honors such as China March 8th Red Flag Bearer, China May 1st Labor Medal and Beijing Expert with Outstanding Contributions.

In clinical work, we often need to build an evaluation system. For example, the classic "Delphi Checklist" in research quality evaluation tool is formed by more than 30 experts through Delphi method. Delphi method, also known as expert consultation method, is core to solicit expert opinions through several rounds of correspondence inquiries anonymously, and then summarize and analyze a comprehensive result. This summary is a semi-quantitative summary method with its obvious objectivity.