ObjectiveTo assess folate nutrition status by investigating dietary folate intakes, food sources and folate level in Shanghai pre-pregnancy couple population.MethodsCross-sectional simple cluster sampling method was conducted on the pre-pregnancy couples at the pre-pregnancy clinics of Minhang District Maternal and Child Health Hospital in Shanghai. Dietary status of participants was surveyed by continuous 3-day 24-hour dietary recall and food frequency table. Pre-pregnancy dietary nutrient supplement questionnaire was applied to record the nutrients supplements intake (e.g folic acid) in the past 3 months. Fasting serum and EDTA anticoagulation blood samples of peripheral venous blood was collected from subjects. The concentration of serum folate and red blood cell folate were detected by chemiluminescence microparticle immunoassay. ResultsA total of 535 subjects participated the survey, including 276 (51.6%) women and 259(48.4%) men. The mean age was (29.4±4.1) years old. The mean dietary folate intake of the study population was 296.3 μg·d-1. Five hundred and three (94.0%) subjects took folic acid supplements lower than the recommended nutrient intake. The mean dietary folate intakes were 267.2 and 327.3 μg·d-1 for women and men, respectively. The median concentrations of serum folate and red blood cell folate were 5.8 and 214.6 ng·mL-1, respectively, with 16.3% and 87.3% being folate-deficient according to serum and red blood cell recommendations. The concentration of serum and red blood cell folate in females were significantly higher than that in males (7.0 vs 4.8 ng·mL-1；231.2 vs 193.7 ng·mL-1, P＜0.001).ConclusionThe majority of pre-pregnancy women in Shanghai are in the status of red blood cell folate deficient, and the dietary folate intake is lower than the recommended value.
ObjectiveTo investigate the antimicrobial resistance profiles of pathogens in Chinese children. MethodsClinical isolates were collected from 10 tertiary children hospitals in China, 2017. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) 2017 breakpoints. ResultsA total of 67 774 isolates were collected, of which 42.1% was gram-positive organisms and 57.9% was gram-negative organisms. The number of five primary pathogens were as follows, Escherichia coli (8 904 isolates), Streptococcus pneumonia (8 354 isolates), Straphylococcus aureus (6 976 isolates), Haemophilus influenza (6 515 isolates), Coagulase negative staphylococci (5 618 isolates). In neonatal group and non-neonatal group, carbapenem resistance Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa accounted for 17.9% and 9.5%, 42.9% and 55.4%, 39.5% and 24.3%, respectively. The methicillin-resistant Staphylococcus aureus (MRSA) was detected from neonatal group (35.8%) and non-neonatal group (39.5%). The penicillin non-susceptible rates of Streptococcus pneumonia in the two groups were 23.2% and 21.7%. The β-lactamase positive rates of Haemophilus pneumonia isolated from the neonatal group and non-neonatal groups were up to 54.8% and 59.9%. ConclusionThis investigation highlights the worrisome trend of antimicrobial resistance in children. Carbapenem-resistant bacteria have increased gradually, which makes a big challenge of clinical effective therapy for pediatric infections.
ObjectiveTo investigate the morphological characteristics of blasts in childhood acute lymphoblastic leukemia (ALL) with MLL gene rearrangement and the correlation with patients' clinical features and outcomes. MethodsThe ALL patients with MLL gene rearrangements treated on Chinese Children Leukemia Group (CCLG)-ALL 2008 protocol at Hematology and Oncology Center of Beijing Children's Hospital were enrolled retrospectively. The ALL patients without MLL gene rearrangement with the same gender to MLL+ patients enrolled at the same term were selected as controls. The MLL+ group was sub-divided into positive and negative sub groups based on the morphological characteristics in blasts. The difference of morphological characteristics between MLL+ and MLL- groups was compared; the clinical features and event-free survival (EFS) between morphological positive and negative subgroups of MLL+ patients were analyzed. Receiver operator curve (ROC) method was used to test the ability of atypical morphological features to identify the outcome of patients. ResultsA total of 26 newly diagnosed patients(12 boys and 14 girls) aging from 4 months to 13years with MLL rearrangement were enrolled between 1st Jan 2011 and 31st May 2018, whom 18 patients were in clinical remission, 5 patients suffered bone marrow relapse and 3 patients did not continue treatment after diagnosis. The control group contained 30 patients(16 boys and 14 girls) without MLL rearrangement aging from 8 months to 14 years. No significant difference of bone marrow morphology was found between ALL patients with or without MLL gene rearrangement, except for a lower percentage and integral value of glycogen staining in patients with MLL gene rearrangement. The granules, nucleoli, vacuoles and pseudopodia of bone marrow blasts were not associated with WBC, gender and age at diagnosis. Nucleoli were found in all six MLL-AF4 positive patients, significantly higher than other subtype, P=0.028. A higher proportion of high MRD (≥10-4) at day 33 was found in patients without pseudopodia, P=0.025. The prognosis of patients with nucleoli in blasts was poorer than those without, with 3-year EFS of (55.0±15.0)% for patients with nucleoli vs. 100% of those without, P=0.049. The 3-year EFS for patients with or without granules was (41.7±22.2)% vs. (83.9±10.4)% , P=0.052, which was close to cut-off of P value. ROC showed that combined analysis of nucleolus and granules features could better predict the MLL+ patients prognosis than separately, with the area under curve of 0.833, 0.786 and 0.705 respectively. ConclusionThe blasts of ALL patients'with MLL gene rearrangements have specific histochemical staining features. Their morphological features are associated with MLL rearrangement subtypes and predict the prognosis of patients.
ObjectiveTo explore the clinical features of Kawasaki disease (KD) complicated with macrophage activation syndrome (MAS) and the biological significance of related gene and protein expression.MethodsClinical data and laboratory results of patients with MAS in KD admitted to Children's Hospital of Chongqing Medical University from August 2008 to June 2017 were retrospectively studied and compared with the patients from published literature. The patients were divided into two groups according to the prognosis: improvement group and poor prognosis group (dead or abandoned therapy).ResultsThe incidences of clinical manifeststions in 9 children with KD complicated with MAS in our study were as follows: hepatosplenomegaly and intravenous immunoglobulin (IVIG) unresponsiveness 100%(9/9), rashes 88.9%(8/9), changes in the extremities 88.9%(8/9), changes in the lips and oral cavity 77.8%(7/9), lymphadenopathy 66.7%(6/9), bilateral conjunctival injection 44.4%(4/9), coronary lesions 88.9%(8/9), incomplete KD 44.4%(4/9). C-reactive protein (CRP) increase, fibrinogen ＜ 1.5 g·L-1 and ferritin level >1 500 ng·mL-1 were found in 8 patients separately. The rates of alanine aminotransferase (ALT) increase, aspartate aminotransferase (AST) increase, hemophagocytic phenomenon in bone marrow and triglyceride (TG)＞3.0 mmol·L-1 were 77.8%(7/9), 66.7%(6/9) , 66.7%(6/9) and 44.4%(4/9), respectively. HLH-related gene and protein expression were measured in 2 children with MAS in KD. Reduced expression of perforin in NK cells was detected in 2 cases, but reduced granzyme B in NK cell and reduced perforin in CTL cells were found in only one case. No mutation of 24 genes related to HLH was found in 2 cases. A total of 27 patients with MAS in KD (including 9 cases in our study) were enrolled based on the literature review. According to the prognosis, 27 cases were divided into improvement group (18 cases) and poor prognosis group (9 cases). The incidence of incomplete KD in poor prognosis group was higher than that in the improvement group (55.6% vs 5.9%, P=0.004). ConclusionMAS complicating with KD should be considered when KD children are with IVIG unresponsiveness, hepatosplenomegaly, elevated AST and ALT, hyperferroteinemia. KD complicated with MAS showed no genetic susceptibility. Reduced perforin expression may be closely related to KD-MAS. Incomplete KD may be one of the risk factors affecting the prognosis of children with KD-MAS.
ObjectiveTo investigate the epidemological and clinical features of Kawasaki disease (KD) in Tongji Hospital Affiliated to Huazhong University of Science and Technology (our hospital) and to explore the risk factors of coronary arteries lesions(CAL) and intravenous immunoglobulin (IVIG) resistant-KD.MethodsThis study is a descriptive, retrospective analysis, which covered patients diagnosed with KD from January 1, 2012 to December 31, 2016 in our hospital. It was designed to study the epidemiological and clinical features of KD and to analyze the differences of related inflammatory and biochemical markers between typical KD and incomplete KD, KD with CAL and without CAL, IVIG-resistant KD and IVIG-sensitive KD.ResultsThere were 725 patients with KD as the primary diagnosis. The median age was (2.7±2.3) years. Among all children, 206 (28.4%) cases were incomplete KD and 509 (71.6%) cases were typical KD. A total of 216 (29.8%) had coronary arteries abnormality and 61 (8.41%) was diagnosed with IVIG-resistant KD. There were 70 cases (9.6%) of KD without the treatment of IVIG. Logistic regression showed that IVIG resistance (OR=5.138，95%CI：1.835~14.836，P=0.002) and higher level of brain natriuretic peptide (NT-proBNP≥1 000 pg·mL-1)(OR=2.723，95%CI：1.110-6.679，P=0.029) were the risk factors of CAL. Also, it presented that the risk factors of IVIG-resistant KD was CAL (OR=2.586, 95%CI: 1.067-6.271, P=0.035).ConclusionIt showed that the incidence of KD is increasing gradually, as well as the incidence of CAL and IVIG-resistant KD in our hospital. IVIG resistance and high levels of BNP (NT-proBNP≥1 000 pg·mL-1) are the risk factors of coronary arteries lesions. Meanwhile, KD with CAL is the risk factor of IVIG-resistant KD.
ObjectiveTo analyze the risk factors for brain injury in preterm infants with necrotizing enterocolits (NEC).MethodsThe retrospective study was conducted in preterm infants with NEC (Bell stage ≥Ⅱ) admitted to the neonatal intensive care unit, Children's Hospital of Fudan University during January 1st, 2012 to August 31st, 2017. The included patients were divided into positive cranial MRI group with white matter grades≥7 or grey matter grades ≥5 and negative group--the rest of the patients, according to MRI grades. Then compare the clinical characteristics between two groups to analyse the risk factors for brain brain injury in preterm infants with NEC. The fitting curve was used to determine the cutoff and the receiver operating characteristics curve (ROC) was used to evaluate the predictive value of risk factors for brain injury.ResultsA total of 110 preterm infants with NEC were enrolled, including 49 in MRI positive group and 61 in negtive group. There were no statistical difference in GA, BW, antenatal steroid use, Apgar 1 min, duration of mechanical ventilation, operation, onset age of NEC, C reaction protein (CRP) and blood culture within 24 h after NEC between the two groups（P>0.05）. However, the incidence of white blood cell (WBC) <4×109·L-1 or > 20 ×109·L-1 and platelet (PLT) level within 24 h after NEC, the rates of Bell stage Ⅲ and intestinal perforation were significantly different （P<0.05）. WBC < 4×109·L-1 or > 20 ×109·L-1 within 24 h after NEC(OR=4.3，95%CI：1.6-11.5) and intestinal perforation(OR=4.7，95%CI：1.3-17.4) were the independent risk factors for brain injury. The area under curve (AUC) of ROC was 0.722 when WBC ≤ 8×109·L-1, and the corresponding cutoff, sensitivity and specificity were 5.2×109·L-1, 68.4% and 71.1%, respectively. While WBC > 8×109·L-1, the AUC was 0.695 and the corresponding cutoff, sensitivity and specificity were 15.5×109·L-1, 61.1% and 77.1%, respectively.ConclusionThe change of WBC within 24 h after NEC and intestinal perforation consist the independent risk factors for brain injury in preterm infants with NEC. WBC < 5.2×109·L-1 or > 15.5×109·L-1 during the 24 h after NEC has certain value to predict brain injury.
ObjectiveTo investigate the risk factors for neonatal infection with intrapartum maternal fever. MethodsA retrospective case-control study was conducted in neonates (gestational age ≥ 37 weeks, singleton) born in Obstetrics and Gynecology Hospital Affiliated to Fudan University (our hospital) from January 1 to December 31, 2016, with maternal fever (temperature peak ≥ 38 °C). According to the diagnostic criteria for neonatal infection in our hospital ［at 12 h to 24 h after birth, blood routine WBC ≥ 50 × 109·L-1 and / or CRP ≥ 20 mg·L-1, or at 24 to 48 h after birth WBC ≥ 30 × 109·L-1 and / or CRP ≥ 8 mg·L-1)］ ,the neonates were divided into infected group and control group. The neonatal gender, gestational age, birth weight, mode of delivery, maternal temperature peak, prenatal blood WBC count and CRP, whether epidural anesthesia, GBS positive, amniotic fluid Ⅲ ° or amniotic fluid odor, premature rupture of membranes ≥ 18 h) were analyzed to investigate the risk factors for neonatal infection.ResultsA total of 323 neonates were included in the analysis, 123 cases in the infected group and 200 cases in the control group. Logistic multivariate regression analysis showed that the mother's temperature over 38.8℃ (OR=11.89, 95% CI: 3.21-67.12), prenatal blood WBC>13.1×109·L-1 (OR=6.50, 95% CI: 1.87-78.25), GBS positive (OR=7.91, 95% CI: 1.77-22.13), amniotic fluid Ⅲ° or amniotic fluid odor (OR: 33.1, 95% CI: 3.34-101.56) and premature rupture of membranes ≥ 18 h (OR=15.12, 95% CI: 5.72-67.39) were the independent risk factors for neonatal infection.ConclusionNeonatal infection was associated with peak prenatal temperature and prenatal blood WBC count of their mother. The rate of neonatal infection was elevated in mothers with fever and other high-risk factors. Epidural anesthesia may cause maternal fever, but may not increase the risk of neonatal infection.
ObjectiveTo study the clinical features of gestational alloimmune liver disease-neonatal hemochromatosis(GALD-NH), and to improve the understanding of GALD-NH.MethodsClinical manifestations and pathological diagnosis process of one patient with GALD-NH were retrospectively analyzed. The GALD-NH related literature was reviewed.ResultsThe patient was a full-term male infant. Onset of the disease was the second day after birth. Clinical characteristics included severe liver function dysfunction, coagulation function dysfunction, oliguria, anasrca (hydrothorax and ascites), thrombocytopenia. The patient died on 43rd day after birth. Pathological anatomy showed severe acute liver failure. Pathologic siderosis of extrahepatic tissues was positive, incluing pancreas and thyroid gland. Liver biopsy showed strong immunostaining of hepatocytes for the C5b-9 complex. Definite diagonosis of GALD-NH was made for this patient. Totally 90 patients with NH were recruited from 12 articles and our report. Main prenatal signs were hydrops fetalis(17/90), oligohydramnion(21/90), intrauterine growth retardation(33/90), and clinical process after birth developed rapidly with abnormality of iron metabolism(65/90), liver function failure(62/90) and severe coagulation function dysfunction(58/90). Extrahepatic siderosis and positive C5b-9 complex of hepatic tissue were confirmed in 48 and 14 patients respectively. The number of patients received Cocktail treatment, IVIG transfusion, blood exchange transfusion(BET), IVIG+BET and liver transplantation were 36, 4, 9, 20 and 13, respectively. Fifty-five patients died and 35 survived. Twenty-eight of survivors were followed and the prognosis was good. ConclusionGALD-NH is rare and fatal, processing quickly after birth in multisystem injuries involving iron metabolism, liver and coagulation. Diagnosis of NH needs presence of extrahepatic siderosis. Treatment strategy includes IVIG infusion and/or BET. Mortality of GALD-NH is high, but prognosis is good for survivor.
ObjectiveTo investigate the clinical and molecular characteristics of an X-linked neutropenia patient caused by gain-of-function WAS mutation.MethodsThe patient's clinical data, including infection history, ANC of peripheral blood, bone marrow cell morphology, hematology inherited disease related gene screening, and routine immunology function evaluation were reviewed. Sanger sequencing was done for verification of WAS mutation. The WAS protein and WAS mRNA expression level of the patient and his parents were detected by flow cytometry and qPCR method respectively. The keyword "X-linked neutropenia" was searched for in the main English and Chinese databases by the time of September 20, 2018. The main clinical phenotypes and genotypes were extracted from related articles.ResultsThe 6-year-old boy had persistent severe neutropenia from 3-month old with tendency of bacterial infection and recurrent fever. The quantity and volume of blood platelet were normal, while ANC was severely decreased for about 6 years. Immunoglobulin E was slightly increased, NK cells decreased (1.63%), and CD4+/CD8+ T cells was slightly reversed (0.99). The bone marrow smear showed maturation arrest of neutrophil precursors at the promyelocyte stage. The second-generation sequencing detected a missense mutation in WAS gene exon 9 c.881T>C (p.I294T), and his mother was the carrier. The relative expression of WAS gene was 0.29 times compared to control. WAS protein expressed about 74.5% in this case which was much lower in classic WAS syndrome patients. Two families and 3 sporadic cases, totally 18 cases and 4 mutation sites (L270P, S272P, I290T, I294T) were screened out. Analysis of the 19 cases (including this case) showed that ANC decreased in 84.2% of the cases, monocytes decreased in 72.2%, and the lymphocyte subset analysis showed that CD4+/CD8+ was inverted by 56.3%. Clinically, bacterial infections and fever were found frequently.ConclusionThe gain-of-function mutation of WAS gene can lead to congenital neutropenia which was characterized by recurrent infection without prominent symptoms. Reduced molecular expression of WAS mRNA and slightly reduced WASP protein are main molecular characteristics.
ObjectiveTo summarize the case of KBG syndrome (macrodontia, mental retardation, characteristic facies, short stature, and skeletal anomalies，KBGS), analyze ANKRD11 gene sequencing results in China, and review the literature to improve the understanding of the disease. MethodsThe clinical data of a patient with KBGS were collected. Whole Exon Sequencing of peripheral blood in the family was done and verified by Sanger method. ANKRD11 mutations from PubMed，Wanfang Database and China National Knowledge Infrastructure up to November 1st, 2018 were searched. The related features along with the clinical and gene mutation spectrums of KBGS cases and 16q24.3 microdeletion cases were summarized. ResultsThe patient, female, 8 years old, presented with "growth retardation". The patient was proportioned short stature with special craniofacial features after birth, and she also presented with short fingers combined with bending, wide gait based, exercise, and language development retardation. ANKRD11 gene was found with c.6792dupC (p. P2271Pfs*8) heterozygous mutation, leading to premature termination of a highly conserved carboxyl terminal protein. A total of 22 articles were retrieved from the literature review, and a total of 155 patients with KBGS including the case reported in this article were analyzed. Among them, 114 patients were with ANKRD11 mutation and 41 patients with 16q24.3 microdeletion. The ratio of male to female in KBGS patients was about 1.5. The clinical manifestations were cranial facial abnormalities, language development delay, mental retardation, learning disability, micrognathia, short finger combined with fifth finger bending, short stature. Congenital heart diseases were detected in the type of ANKRD11 mutant and 16q24.3 microdeletion for 12.2% and 28.9%, respectively. ITP was detected in the type of 16q24.3 microdeletion for 12.2%. ConclusionAbnormal manifestations of central nervous system such as language development retardation, learning disabilities, and mental retardation are KBGS-specific phenotypes, which combined with typical craniofacial abnormalities (triangular face, wide eye distance, wide nasal bridge, abnormal philtrum), micrognathia, short and fifth finger bending need to consider ANKRD11 gene mutation. Patients with 16q24.3 microdeletion may be combined with congenital heart disease and ITP.
ObjectiveTo investigate the clinical and laboratory characteristics of Menkes disease.MethodsThe clinical, laboratory, imaging and gene expression of 2 children diagnosed as Menkes's disease in 1 family were retrospectively analyzed.ResultsTwo children were all boys.The clinical manifestations of the younger brother began at 4 months after birth, including pale skin, pudgy cheeks, inguinal hernia, peculiar kinkyhair, funnel chest, epilepsy and mental retardation. The child's brother developed backward since childhood, and the rehabilitation treatment was invalid，died 1 year ago. Plasma ceruloplasmin in 2 cases was 80 mg·L-1 and 92.4 mg·L-1, respectively. Two children's hair was observed under the light microscope with distorted and beaded changes. The delayed myelination of the brain MRI, the changes of bilateral cerebral and cerebellar atrophy, the increase of the cerebral surface vascular circuitous, bilateral basal ganglia and the abnormal signal of the cerebral foot were observed in the probard. The brain MRA+MRV showed that the large arteries were circuitous, the branches of the arteries and the superficial vein twisted into a group. The child did not find the ATP7A gene existence of large fragment variation, However, there is a small variation of c.2172+5_2172TGAAG （TGAAT was inserted between the 5th and 6th nucleotides in intron after nucleotide 2 172 of coding region） in ATP7A gene, which is shear variation.The brother was the same as the heterotopic, and the mother was a normal carrier. ConclusionMenkes disease is a hereditary copper metabolic disorder. The main manifestations of the progressive neurodamage are the special facial features and hair changes, as well as the morphological changes of brain atrophy and cerebral vessels, combined with laboratory examination, head image and gene detection can be confirmed.
CHEN Qiu-yu, SUN Bi-jun, MENG Xin, WANG Wen-jie, YING Wen-jing, ZHOU Qin-hua, HUI Xiao-ying, SUN Jin-qiao, HOU Jia, LIU Dan-ru, WANG Ying, WANG Xiao-chuan
ObjectiveTo investigate the clinical features and genetic variation of WHIM syndrome caused by CXCR4 gene mutation.MethodsThe clinical data and whole exome sequencing results of 3 children with WHIM syndrome caused by mutation of CXCR4 gene were retrospectively analyzed. Systematic search and literature review were conducted to collect patients with WHIM syndrome, and to summarize clinical manifestations and gene mutation information.ResultsThree children with WHIM syndrome were all males. The diagnosis age of 3 patients was 11 years, 13 months and 5 years, respectively. All cases had recurrent infection, 1 case developed diabetes, no patients had developed warts. After the treatment with G-CSF, white blood cells could rise to normal, but were prone to decline. All patients showed lymphopenia and neutropenia, but not periodically. Immunoglobulin decreased in all 3 cases. Gene results of whole exome sequencing showed all of the three patients had the same mutation: C-terminal heterozygous exon 2 of CXCR4 gene, and a base substitution mutation (1000C>T) occurred at the second exon cleavage site of CXCR4 gene. A total of 45 English articles and 1 Chinese literature were retrieved from the database. Altogether with the 3 patients in this study, 74 patients with WHIM syndrome were reported so far.ConclusionWHIM syndrome is a rare autosomal dominant genetic disease. Patients can present with warts, recurrent infection, leukopenia and myelokathexis. WHIM syndrome should be considered when young patients manifest symptoms described above except for the warts, thus gene analysis is critical for the diagnosis of the disease.
