Objective:To understand the management of children with pediatric acute liver failure (PALF) in pediatric intensive care unit (PICU).Methods:A retrospective case-control study was conducted. A total of 101 children with PALF hospitalized in PICU of Beijing Children′s Hospital from July 2017 to October 2022 were included. Demographic, clinical management and prognosis data were collected. According to whether PALF was the main diagnosis, the patients were divided into primary diagnosis group and complication group. The primary diagnosis group was subdivided into effective group and ineffective group with routine treatment (except liver transplantation). The intergroup comparisons were performed using independent samples t-test, Mann-Whitney U test, χ2 test or Fisher exact test. Multivariate Logistic regression analysis was employed to identify risk factors associated with prognosis. Results:Among the 101 children with PALF, 58 were male and 43 were female, with an age of 30 (10, 103) months, 60 cases in primary diagnosis group and 41 cases in complication group. There were no significant differences in prothrombin time (PT) and international normalized ratio (INR) between the two groups (both P>0.05), while the total bilirubin, direct bilirubin and blood ammonia were all significantly higher in the primary diagnosis group (all P<0.05). Unoriginal liver failure (25 cases (42%)) and poisoning (13 cases (22%)) were the most common causes of PALF in the primary diagnosis group, while shock (17 cases, 43%) and hemophagocytic syndrome (14 cases (34%)) in the complication group. The mortality rate of the main diagnosis group was significantly lower than that of the complication group (25% (15/60) vs. 61% (25/41), χ2=13.18, P<0.001), as well as the incidence of combined organ function injury, while the amount of plasma used and the ratio of plasma exchange times to PICU hospitalization days were significantly higher (all P<0.05). In the primary diagnosis group, there were 32 cases (53%) in the effective group and 28 cases (47%) in the ineffective group. In the ineffective group, 15 cases (54%) died and 13 cases (46%) were transferred to another site for liver transplantation assessment. The hospitalization time of PICU in the effective group was significantly longer than that in the ineffective group, while the ratio of plasma exchange times to PICU hospitalization days, the average daily hours of continuous renal replacement therapy (CRRT), the rate of CRRT and the average daily plasma dosage in the effective group were all significantly lower than those in the ineffective group (all P<0.05). The worst PT, INR and blood ammonia, and the stage 4 hepatic encephalopathy morbidity and significant bleeding rate in the effective group were all significantly lower than those in the ineffective group (all P<0.05). Multivariate Logistic regression analysis showed that after adjusting for age, sex, total bilirubin, INR and blood ammonia, stage 4 hepatic encephalopathy was the independent risk factor for the failure of routine treatment of PALF ( OR=84.16,95% CI 4.04-1752.37, P=0.004). Conclusions:PT and INR could not specifically represent liver synthetic function in some PICU patients, so current PALF diagnostic criteria for PICU children has limitations. Complicated with stage 4 hepatic encephalopathy was an independent risk factor of the failure of conventional treatment in patients with PALF.

Age-related macular degeneration (AMD) is an age-related neurodegenerative eye disease characterized by degeneration and progressive death of retinal pigment epithelium (RPE) and photoreceptor cells. In recent years, as a new treatment for AMD, stem cell therapy has attracted wide attention in the field of AMD, and has become a current research hotspot. Although stem cell therapy carries risks such as increased incidence of cancer and immune rejection, it significantly promotes damaged photoreceptor cells and retinal cells by differentiating into RPE cells and other retinal cell types, as well as secreting neurotrophic factors and extracellular vesicles. In particular, the development of embryonic stem cell-derived RPE cells, its cryopreservation technology and the advancement of plasmid, adeno-associated virus, Sendai virus and other delivery technologies have laid a solid foundation for stem cell therapy of AMD. As a new method to prevent retinal damage and photoreceptor degeneration, stem cell neuroprotective therapy has shown great potential, and with the continuous maturity and improvement of these technologies, stem cell therapy is expected to provide new ideas for the prevention and treatment of AMD in the future.

Objective:To understand the management of children with pediatric acute liver failure (PALF) in pediatric intensive care unit (PICU).Methods:A retrospective case-control study was conducted. A total of 101 children with PALF hospitalized in PICU of Beijing Children′s Hospital from July 2017 to October 2022 were included. Demographic, clinical management and prognosis data were collected. According to whether PALF was the main diagnosis, the patients were divided into primary diagnosis group and complication group. The primary diagnosis group was subdivided into effective group and ineffective group with routine treatment (except liver transplantation). The intergroup comparisons were performed using independent samples t-test, Mann-Whitney U test, χ2 test or Fisher exact test. Multivariate Logistic regression analysis was employed to identify risk factors associated with prognosis. Results:Among the 101 children with PALF, 58 were male and 43 were female, with an age of 30 (10, 103) months, 60 cases in primary diagnosis group and 41 cases in complication group. There were no significant differences in prothrombin time (PT) and international normalized ratio (INR) between the two groups (both P>0.05), while the total bilirubin, direct bilirubin and blood ammonia were all significantly higher in the primary diagnosis group (all P<0.05). Unoriginal liver failure (25 cases (42%)) and poisoning (13 cases (22%)) were the most common causes of PALF in the primary diagnosis group, while shock (17 cases, 43%) and hemophagocytic syndrome (14 cases (34%)) in the complication group. The mortality rate of the main diagnosis group was significantly lower than that of the complication group (25% (15/60) vs. 61% (25/41), χ2=13.18, P<0.001), as well as the incidence of combined organ function injury, while the amount of plasma used and the ratio of plasma exchange times to PICU hospitalization days were significantly higher (all P<0.05). In the primary diagnosis group, there were 32 cases (53%) in the effective group and 28 cases (47%) in the ineffective group. In the ineffective group, 15 cases (54%) died and 13 cases (46%) were transferred to another site for liver transplantation assessment. The hospitalization time of PICU in the effective group was significantly longer than that in the ineffective group, while the ratio of plasma exchange times to PICU hospitalization days, the average daily hours of continuous renal replacement therapy (CRRT), the rate of CRRT and the average daily plasma dosage in the effective group were all significantly lower than those in the ineffective group (all P<0.05). The worst PT, INR and blood ammonia, and the stage 4 hepatic encephalopathy morbidity and significant bleeding rate in the effective group were all significantly lower than those in the ineffective group (all P<0.05). Multivariate Logistic regression analysis showed that after adjusting for age, sex, total bilirubin, INR and blood ammonia, stage 4 hepatic encephalopathy was the independent risk factor for the failure of routine treatment of PALF ( OR=84.16,95% CI 4.04-1752.37, P=0.004). Conclusions:PT and INR could not specifically represent liver synthetic function in some PICU patients, so current PALF diagnostic criteria for PICU children has limitations. Complicated with stage 4 hepatic encephalopathy was an independent risk factor of the failure of conventional treatment in patients with PALF.

Age-related macular degeneration (AMD) is an age-related neurodegenerative eye disease characterized by degeneration and progressive death of retinal pigment epithelium (RPE) and photoreceptor cells. In recent years, as a new treatment for AMD, stem cell therapy has attracted wide attention in the field of AMD, and has become a current research hotspot. Although stem cell therapy carries risks such as increased incidence of cancer and immune rejection, it significantly promotes damaged photoreceptor cells and retinal cells by differentiating into RPE cells and other retinal cell types, as well as secreting neurotrophic factors and extracellular vesicles. In particular, the development of embryonic stem cell-derived RPE cells, its cryopreservation technology and the advancement of plasmid, adeno-associated virus, Sendai virus and other delivery technologies have laid a solid foundation for stem cell therapy of AMD. As a new method to prevent retinal damage and photoreceptor degeneration, stem cell neuroprotective therapy has shown great potential, and with the continuous maturity and improvement of these technologies, stem cell therapy is expected to provide new ideas for the prevention and treatment of AMD in the future.

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 investigate the clinical characteristics and prognosis of children with septic shock caused by invasive pneumococcal diseases (IPDs) in pediatric intensive care unit (PICU).Methods:The clinical data of children diagnosed as septic shock caused by IPDs and hospitalized in the intensive care unit (ICU) of Beijing Children′s Hospital, Capital Medical University and the PICU of Henan Children′s Hospital from January 2013 to August 2019 were retrospectively collected, and the clinical characteristics and prognosis of these patients were analyzed.Results:Twenty-one children were included, with a median age of 1.2 (0.75, 3.90) years old.The pediatric index of mortality 2 (PIM-2) at admitting was (23.3±29.6)%, and 6 cases had underlying diseases.Main sites of infection included blood flow (20 cases) and suppurative meningitis (15 cases). The drug sensitivity test was performed on 18 children, among who 9 cases were sensitive to Penicillin, 10 cases to Cefepime, 11 cases to Cefotaxime and 10 cases to Meropenem.All 18 patients were sensitive to Vancomycin and Linezolid.Seven cases and 13 cases were treated with sensitive antibiotics at the disease onset and before septic shock, respectively.In 21 cases whose lactic acid level was (6.1±4.6) mmol/L, the shock redress time of 10 cases was (10.9±10.1)h, and 13 cases (61.9%) died (14.6±12.2) hours after septic shock, among who 10 died of transforamed magna herniation.The PIM-2 score at admitting into PICU and the rate of intracranial hypertension crisis in the death group were significantly higher than those in the survival group [(37.1±30.3)% vs.(0.9±1.3)%, 69.9% (9/13 cases) vs.25.0% (2/8 cases)](all P<0.05). There was no significant difference in age and the utilization rate of effective antibiotics before septic shock between the two groups (all P<0.05). Four of the surviving 8 children had severe cerebral functional disability. Conclusions:Septic shock caused by IPD is more common in children under 5 years old, and the most common sites are blood flow and intracranial infection.It has high resistance rate against Cephalosporins and Carbopenem.Patients with purulent meningitis are easy to develop intracranial hypertension crisis, which has an extremely high mortality and morbidity, so it needs to be identified and treated early.

Objective: To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC). Methods: Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled. Samples of carcinoma tissue, para-carcinoma tissue and corresponding normal liver tissue were collected from each case. DNA was extracted from three kinds of tissue samples. HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA. The integrated HBV fragments were determined by PCR products sequencing. Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting. Statistical analysis was performed using t test, analysis of variance, and χ² test. Results: Among the 18 CHB patients complicated with HCC, integration of HBVX gene was found in 13 carcinoma tissue samples, 16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples. The difference was statistically significant (χ²=6.353, P=0.037). Of the 18 patients, the protein expressions of ZBTB20 in carcinoma tissue, para-carcinoma tissue and corresponding normal tissue were (50.14±11.25)%, (40.71±7.17)% and (39.06±5.17)%, respectively, which was statistically different (F=9.420, P<0.01). HBVX gene integration was detected at ZBTB20 locus in five patients. The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue, para-carcinoma tissue and corresponding, normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)% vs (55.06±7.06)%, para-carcinoma tissue (32.06±2.61)% vs (44.04±5.24)%, corresponding normal tissue (34.66±5.59)% vs (40.76±4.04)%, t=4.205, 4.821 and 2.589, respectively, all P<0.05). Conclusions Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue. Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20.

Objective To investigate the outcomes of fetuses with hemolytic anemia caused by red cell alloimmunization following intrauterine transfusion (IUT),and to analyze the influence of hydrops fetalis on IUT treatment.Methods A retrospective analysis was conducted on 70 fetuses,who were admitted to the Fetal Medicine Center,the First Affiliated Hospital of Sun Yat-sen University from January 2005 to May 2018,with hemolytic disease requiring IUT.Clinical data of the fetuses and the gravidas were collected and divided into hydrops group (17 cases) and non-hydrops group (53 cases) based on their conditions before IUT.Results of routine blood tests before and after the first IUT,gestational age at the first IUT,prognosis and outcomes of the fetuses were compared between two groups.t-test,rank-sum test,Chi-square test (or Fisher's exact test) and multivariant logistic regression analysis were used for data analysis.Results Totally,the 70 fetuses underwent 231 times of IUT.Compared with the non-hydrops group,the hydrops group had a significantly increased incidence of severe anemia [14/17 vs 47.2％ (25/53),x2=6.458,P=0.011],but decreased hemoglobin [(38.5 ± 21.4) vs (68.7± 19.3) g/L,t=5.471,P＜0.001] and hematocrit level [0.110 (0.044-0.246) vs 0.222 (0.077-0.299),Z=-4.390,P＜0.001] before the first IUT.After the IUT,the survival rate of the fetuses in hydrops group was significantly lower than that of the non-hydrops group [11/15 vs 94.3％ (50/53),P=0.038].There was no significant difference in gestational age at birth,birth weight,neonatal hemoglobin level at birth,the incidence of exchange transfusion,the number of blood transfusions required or the incidence of severe neonatal complication between the two groups (all P＞0.05).Logistic regression analysis indicated that the fetal hydrops was an independent risk factor for fetal survival (OR=12.8,95％CI:1.2-136.4,P=0.035).Conclusions Hydrops fetalis might reduce the survival rate of fetal hemolytic disease after 1UT.

Objective To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT)Methods The clinical data of 2 patients with congenital myasthenia syndrome were collected,and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital,Capital Medical University.The clinical features and gene mutation characteristics were analyzed,and the patients were followed-up for therapeutic efficacy.Results The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively.The two patients were admitted to the PICU due to dyspnea,cyanotic episodes that required intubation.The patients had repeated apnea and became ventilator dependent.Case 1 died due to refusal of any treatment.Case 2 had a tracheotomy,and gradually weaned from ventilator after using pyridostigmine.The hospitalization of case 2 lasted 162 days.Case 2 was followed up to the age of 3 years and 4 months,and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation.Both cases were negative for anti-AChR,anti-acetylcholinesterase,anti-MuSK antibodies.Neostigmine test was negative in case 1 and suspiciously positive in case 2.Low-frequency repetitive nerve stimulation testing of case 2 was negative.Cranial MRI scans of both cases showed brain atrophy-like change.Genetic testing showed compound heterozygous deletions (exon 4,5,6) and pathogenic variant c.914T＞C (p.I305T) in CHAT in case 1,compound heterozygous variants c.1007T＞C (p.I336T) and c.64C＞T (p.Q22X) in CHAT in case 2.To our knowledge,compound heterozygous deletions (exon 4,5,6) and p.Q22X were novel,previously unreported variants.Conclusion CMS-EA usually presents at birth or in the neonatal period with hypotonia,ptosis,dysphagia due to severe bulbar weakness,and respiratory insufficiency with cyanosis and apnea.Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.

OBJECTIVETo use array comparative genomic hybridization (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) to detect unbalanced rearrangements in 4 cases suspected to have chromosome disease but were undetected with conventional karyotype analysis, and to assess the applicability of array-CGH and MLPA for detection of unbalanced translocation.

METHODSGenomic DNA was extracted with standard procedures. All cases were analyzed by array-CGH and subtelomeric MLPA.

RESULTSAll of the cases were identified to have unbalanced translocations by array-CGH analysis, among which 3 were consistent with subtelomeric MLPA analysis. For the remaining one, its chromosomal abnormality was not detected by MLPA as the imbalance has occurred outside of target regions.

CONCLUSIONBoth array-CGH and MLPA techniques can complement conventional karyotyping for detecting unbalanced translocations. The combination features both high resolution and efficiency for clinical use.

Adult ; Child ; Chromosome Deletion ; Chromosome Duplication ; Comparative Genomic Hybridization ; Humans ; Infant ; Karyotyping ; Male ; Multiplex Polymerase Chain Reaction ; Phenotype ; Translocation, Genetic