Objective To investigate the clinical characteristics and risk factors of the occurrence of hypoxic hepatitis(HH)in children with shock.Methods Clinical data(general situation,clinical situation and prognosis)of 234 children with different types of shock admitted to the pediatrics department of Hainan Women and Children's Medical Center from January 2016 to December 2023 were collected.Serum biochemical indexes on day 1(d1),day 2(d2),day 3(d3),day 5(d5),day 7(d7)of children with shock were collected,including serum alanine aminotransferase(ALT),glutamate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(ALP),albumin(ALB),total bilirubin(TBIL),urea nitrogen(BUN),C reactive protein(CRP),international standardized time(INR)and lactate.And the clinical characteristics and risk factors of the occurrence of HH in children with shock were analyzed.Results A total of 234 cases(150 cases of males)of different types of shock in children were enrolled,ages ranged from 1 month to 16 years old.According to whether developed HH,the children with shock were divided into HH group(32 cases)and non-HH group(202 cases).The total incidence of HH was 13.7%(32/234).Septic shock was the main disease of the occurrence of HH in children with shock,accounting for 65.63%(21/32).According to the prognosis,children with shock combined HH were divided into survival group(17 cases)and death group(15 cases).The case fatality rate of children with shock combined HH was 46.9%.The ALT and AST values in children with shock combined HH were more than 20 times of the upper limits of normal ranges.The peak values of enzymatic indexes in the survival group appeared at the onset time d 1 to d 2,they were close to the normal ranges at the onset time d7,while the enzymatic indexes in the death group were higher than the normal ranges during the whole disease stage.Compared with the survival group,the peak values of ALT,AST,ALP,TBIL,CRP,BUN,and INR in the death group were obviously higher(P<0.05,both).The lowest value of ALB in the death group was lower than that in the survival group(P<0.05).The results of multivariate Logistic regression analysis showed that pediatric critical illness score(PCIS),lactate,multiple organ dysfunction syndrome(MODS),decompensated shock and cardiogenic shock were the risk factors for the occurrence of HH in children with shock(P<0.05 or 0.01),and left ventricular ejection fraction(LVEF)and mean arterial pressure(MAP)were the risk factors of the death of HH in children with shock(P<0.01).Conclusions Children with shock who have the risk factors as decreased PCIS,increased lactate level,MODS,decompensated shock and cardiogenic shock are apt to suffer from HH.Poor prognosis in the chil-dren with shock combined HH is associated with worse condition and lower LVEF.There is a high fatality rate of shock combined HH in children,so that liver function indicators should be closely monitored to early detect HH,and reasonable treatment should be given.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Objective:To review the clinical outcomes following perinatal multidisciplinary diagnosis and treatment of fetal D-transposition of great arteries (D-TGA).Methods:This retrospective analysis involved 37 fetuses (two fetuses were one of the twins) with D-TGA that were diagnosed by prenatal ultrasound at the Women and Children's Hospital, Qingdao University from January 2016 to December 2020. All the subjects received perinatal multidisciplinary diagnosis and treatment, from the Departments of Fetal Medicine, Genetics, Obstetrics, Ultrasonography, Pediatric Cardiology, Neonatology, etc., and the outcomes were described and summarized.Results:The detection rate of D-TGA was 0.059% (37/62 413), among which intact ventricular septum with D-TGA accounted for 56.8% (21/37) and ventricular septal defect with D-TGA for 43.2% (16/37). All the 37 cases were observed with normal nuchal translucency and four of them were at high risk in fetal Down syndrome screening. All the 31 cases who received non-invasive cell-free fetal DNA screening had normal results and two of 26 cases who received amniocentesis for karyotype analysis and chromosome microarray analysis were abnormal. In terms of pregnancy outcome, 19 pregnancies (51.4%) were terminated, of which 10 cases were terminated for medical reasons and others for non-medical reasons, and 18 cases gave birth to alive body (48.6%, 18/37). Postnatal ultrasound re-examination of one neonate revealed D-TGA with ventricular septal defect, patent ductus arteriosus, and bicuspid pulmonary valve malformation and severe hypoxia and acidosis occured. The patient was discharged after withdrawing treatment and was lost to follow-up. The other 17 neonates all underwent successful surgical treatment with a mean age of (10.2±6.0) d and length of hospital stay of (26.3±9.3) d. Postoperative follow-up (3.3±1.2) years showed all with good cardiac function.Conclusion:Perinatal multidisciplinary diagnosis and treatment of D-TGA can improve the success rate of postnatal treatment and prognosis.

Objective To investigate the effect of heat stress on the expression of Toll-like receptor 4 (TLR4) and peripheral blood T regulatory cells (Treg) in splenic cells of rats.Methods Senventy-two SD rats were divided into 20 ℃ control group and 37 ℃ group.Each group was divided into non stimulation,bacterial lipopolysaccharide (LPS) stimulation and concanavin A (Con-A) stimulation subgroup.Each subgroup had 1,12,48 h and 168 h observation points,and flow cytometry was used to determine the level of TLR4 and Treg.Results The TLR4+ immunocompetent cells in the spleen was decreased from 1 h to 168 h in every subgroup of the 37 ℃ group compared to the 20 ℃ control group (P＜0.05).The level of CD4+CD25+ Treg in the peripheral blood in rats from 1 to 48 h was significantly decreased (P＜0.05) and slightly increased at 168 h in LPS stimulation subgroup in the 37 ℃ group compared to the 20 ℃ control group.The level of CD4+ CD25+ Foxp3+ Treg in the peripheral blood in rats at 12 h were significantly increased in non-stimulation and concanavalin A (Con-A) stimulation subgroups in the 37 ℃group,and were significantly decreased at 168 h in every subgroup of the 37 ℃ group compared with 20 ℃ control group (P＜0.05).The level of CD8+CD25+ Treg in the peripheral blood in rats was significantly increased at 1 h and 168 h in the 37 ℃ hot and humid group in the every subgroup whencompared with the 20 ℃ control group (P＜0.05).The level of CD8+ CD25+Foxp3+ Treg in the peripheral blood in rats was significantly decreased at 1 h and 48 h in the every subgroup,and was significantly increased at 12 h and 168 h in the non-stimulation and LPS stimulation subgroups in the 37 ℃ group compared to the 20 ℃ control group (P＜0.05).Conclusion High temperature and damp heat can destroy the innate immunity and alter the functional state of adaptive immunity in rats.

Objective: To investigate the spectrum of mutations in families with benign familial neonatal-infantile epilepsy (BFNIE) . Methods: Clinical data and peripheral blood DNA samples of all BFNIE probands and their family members were collected from Peking University First Hospital between December 2012 and April 2016. Clinical phenotypes of affected members were analyzed. Genomic DNA was extracted from peripheral blood samples with standard protoco1. Mutations in PRRT2 were screened using Sanger sequencing. For families that PRRT2 mutations were not detected by Sanger sequencing, candidate gene mutations were further screened by next-generation sequencing for epilepsy. Results: A total of 7 families were collected. Of the 30 affected members, 15 were male and 15 were female. The age of epilepsy onset was from 2 days to 6 months. Genetic testing led to the identification of gene mutations in all families. One family had the PRRT2 hotspot mutation (c.649dupC). Three families had missense SCN2A mutations (c.2674G>A/p.V892I, c.2872A>G/p.M958V, and c.2627A>G/p.N876S) . Both c.2872A>G/p.M958V and c.2627A>G/p.N876S were novel SCN2A mutations. Three families had KCNQ2 mutations. Two of them had missense mutations (c.958G>A/p.V320I and c.998G>A/p.R333Q) . The KCNQ2 mutation c.958G>A/p.V320I was novel. One family had a gene deletion of KCNQ2, which also extended to the adjacent gene, CHRNA4; and the deletion involved all the exons of KCNQ2 and CHRNA4. Conclusions Mutations in KCNQ2, SCN2A, and PRRT2 are genetic causes of BFNIE in Chinese families. The detection rate for gene mutations is high in BFNIE families. KCNQ2 and SCN2A mutations are common in BFNIE families. SCN2A mutations (c.2872A>G/p.M958V and c.2627A>G/p.N876S) and KCNQ2 mutation (c.958G>A/p.V320I) are novel mutations.

Objective: To summarize the clinical features of TBC1D24 gene mutations associated with epilepsy. Methods: All the patients with TBC1D24 gene compound heterozygous mutations were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2015 to July 2017, and the features of clinical manifestations, electroencephalogram, and neuroimaging were analyzed. Results: Eighteen cases with TBC1D24 gene compound heterozygous mutations were included. The age of seizure onset was 1 day to 8 months, and the median age was 90 days. Seizure types included generalized tonic-clonic seizures (GTCS) in 3 cases, focal seizures in 18 cases, myoclonus in 18 cases, and 17 cases had focal myoclonus and myoclonus status. The focal myoclonus involving one or multiple muscle groups, sometimes migrating and alternating, lasting up to minutes to several days, and could be terminated by sleep or sedation drugs. In 11 cases, myoclonus was exacerbated by fever or infections, and 2 cases developed into myoclonic status during infection, in a severe case with the loss of consciousness. The magnetic resonance imaging (MRI) of seven patients was abnormal, including cerebral atrophy or cerebellar atrophy with abnormal signals. Segment myoclonus was captured in 10 patients, but without correlated epileptiform discharges. There were ten cases had varying degrees of developmental delay, 7 were normal, and one patient died of status epilepticus at the age of 4 months. Three cases had hearing disorders. In the 18 patients, the clinical phenotype of 4 cases consisted of epilepsy of infancy with migrating focal seizures, 2 with progressive myoclonus epilepsies, 1 with Dravet syndrome, 1 with DOORS syndrome, and 3 with unclassified epileptic encephalopathy. Conclusions The clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated by sleep or sedation drugs. Mental retardation involved or not, neuroimaging could present with cerebral atrophy or cerebellar atrophy with abnormal signals.

Objective To investigate the gene mutations in benign familial infantile epilepsy(BFIE)in Chi-na. Methods Data of all BFIE probands and their family members were collected from Peking University First Hospital and other three hospitals between October 2006 and June 2017. Clinical phenotypes of affected members were analyzed. Genomic DNA was extracted from peripheral blood samples with standard protocol. Mutations in PRRT2 were screened using Sanger sequencing. For families that PRRT2 mutations were not detected by Sanger sequencing,candidate gene mutations were further screened by next - generation sequencing. Results A total of 71 families including 227 affected members were collected. Genetic testing led to the identification of gene mutations in 52 families (52 / 71,73. 2％). Forty - three families had PRRT2 mutations (43 / 71,60. 6％),including 40 families with frameshift mutations(hotspot mutations c. 649_650insC and c. 649delC were detected in 29 families and 6 families,respectively),one family with nonsense mutation,one family with a loss of a stop codon,and one family with a microdeletion of the gene. C. 560_561insT and c. 679C > T were novel PRRT2 mutations. Five families had SCN2A mutations. All SCN2A mutations were missense mutations(c. 668G > A,c. 752T > C,c. 1307T > C,c. 4835C > G,c. 1737C > G). Mutation c. 752T > C, c. 1307T > C,c. 4835C > G,and c. 1737C > G were novel mutations. Three families had KCNQ2 mutations. All KCNQ2 mutations were missense mutations(c. 775G > A,c. 237T > G,c. 1510C > T). Mutation c. 237T > G and c. 1510C > T were novel mutations. One family had a novel GABRA6 mutation c. 523G > T. In 71 BFIE families,16 families had mem-bers who showed paroxysmal kinesigenic dyskinesias(PKD)and subclassified as infantile convulsions with paroxysmal choreoathetosis syndrome(ICCA). Fifteen ICCA families were found having PRRT2 mutations (15 / 16,93. 8％). The remaining ICCA family was not detected with any pathogenic mutation. Conclusion There is high frequency of gene mutations in BFIE families. Mutations in KCNQ2,SCN2A,and PRRT2 are genetic causes of BFIE. PRRT2 is the main gene responsible for BFIE. GABRA6 mutation might be a new cause of BFIE.

Objective: To investigate the clinical and neuroimaging characteristics of acute encephalopathy (AE) after status epilepticus (SE) of patients with Dravet syndrome (DS). Method: The clinical data of DS patients who had AE (coma ≥24 h) after SE were retrospectively collected from February 2005 to August 2016 in Peking University First Hospital and SCN1A gene tests were performed.The clinical and neuroimaging features were summarized. Result: Twenty-two patients (9 males and 13 females) with AE were collected among 412 DS patients during follow-up.Of which 18 patients had SCN1A gene mutations while the remaining 4 patients had no SCN1A gene mutations.The onset age of AE was between 6 months and 10 years.The duration of SE varied between 40 minutes and 9 hours.Prior to the onset of SE, twenty-one patients had high fever, and one patient had normal temperature.Coma lasted from 2 days to 20 days.Nine patients died after the AE, and 13 patients survived with massive neurological regression.From AE to the last visit, the median time of follow-up was 2 years and 3 months (from 7 months to 4 years and 4 months). Nine of 13 survivors had varied improvement in motor, language and cognition, while the remaining 4 patients had no significant improvement.After AE, there were 6 patients with seizure-free, 4 patients with reduced seizures, and 3 patients with no change in seizure frequency, moreover, spasm occurred in 2 patients.Six patients had brain magnetic resonance imaging (MRI) in acute phase and showed bilateral (2 patients) or unilateral (4 patients) hemisphere edema, accompanied by subcortical white matter hyperintense signal in T1 and T2 weighted images in two patients.The neuroimaging of 13 survivors demonstrated diverse cortical atrophy during recovery phase, among which 4 patients showed cerebellar atrophy, one patient had right pontine atrophy, 4 patients accompanied by signal abnormalities in subcortical and periventricular white matter, 2 patients showed right hippocampal sclerosis, and one patient showed signal abnormalities in bilateral basal ganglia. Conclusion SE is more prone to occur in Dravet patients who have high fever.It may result in AE or even death in severe cases.Survivors will leave severe neurological sequelae.The neuroimaging shows brain edema in acute phase.In recovery phase the neuroimaging shows diverse brain atrophy, moreover, a few patients may be associated with cerebellar or pontine atrophy, hippocampal sclerosis or abnormal signals in white matter or basal ganglia.

Objective To investigate the changes of B lymphocyte subsets ( naive B cells, memory B cells and plasmablasts) in peripheral blood of patients with rheumatoid arthritis ( RA) and their correla-tions with the clinical manifestation and laboratory indexes.Methods Sixty-six patients with RA were di-vided into two groups including the group with active RA and the group with inactive RA according to the dis-ease activity score in 28 Joints (DAS28).A control group with healthy subjects was set up accordingly.The distributions of B lymphocyte subsets in peripheral blood samples were detected with flow cytometry analysis and their correlations with clinical manifestations and laboratory indicators were analyzed.Results ( 1 ) Compared with healthy subjevts, the mean fluorescence intensities ( MFIs) of CD19 and the percentages of memory B cells in peripheral blood of the patients with RA were significantly decreased, while the percenta-ges of naive B cells were increased (P<0.05).The percentages of plasmablasts in the patients with active RA were significantly increased as compared with those of healthy subjects and the patients with inactive RA (P<0.05).(2) The percentages of plasmablasts in peripheral blood of the patients with RA were positively correlated with the joint tenderness count, joint swelling count and joint swelling index (P<0.05).(3) A positive correlation was found between the MFIs of CD19 and the erythrocyte sedimentation rates ( ESRs ) among the patients with RA.The percentages of plasmablasts were positively correlated with C reaction pro-tein (CRP) and anti-cyclic citrullinated peptide (anti-CCP) antibody (P<0.05).(4) The percentages of plasmablasts were also positively correlated with the DAS28 among the patients with RA ( R2=0.343, P<0.01).Conclusion The distributions of B lymphocyte subsets varied among the patients in different stages of RA, which were related to the patient′s clinical symptoms and laboratory indexes.The study suggested that different subsets of the B lymphocytes might play an important role in the pathological process of RA.