Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Objective: To analyze the genotypes and clinical phenotypes of patients with epilepsy associated with IQSEC2 gene variants. Methods: The genotypes, seizure types, electroencephalogram, neuroimage of 6 patients with IQSEC2 gene variants in the Department of Pediatrics, Peking University First Hospital from July 2019 to October 2021 were analyzed. Results: There were 5 males and 1 female. Six variants were de novo, including 2 frameshift variants (c.3801_3808dup/p.Q1270Rfs*130, c.1459_1460delAT/p.M487Vfs*2), 2 nonsense variants (c.3163C>T/p.R1055*, c.1417G>T/p.E473*), 1 in-frame deletion (c.2295_2297del/p.N765del) and 1 missense variant (c.2293A>G/p.N765D). Age at seizure onset ranged from 3 months to 2 years and 5 months. Multiple seizure types were observed, including epileptic spasms in 5 patients, focal seizures in 5 patients, tonic seizures in 3 patients, myoclonic seizures in 3 patients, atypical absence seizures in 2 patients and atonic seizures in 2 patients. All 6 patients showed global developmental delay before seizure onset. There were other clinical manifestations, including autistic features in 3 patients, microcephaly in 3 patients, dystonia in 2 patients and binocular esotropia in 1 patient. The electroencephalogram showed slow background activity and hypsarrhythmia in all 6 patients. Brain magnetic resonance imaging showed abnormal in 5 patients and normal in 1 patient. Five patients were diagnosed with infantile spasms. Among them, 4 patients had late-onset infantile spasms. One patient was unclassified developmental epileptic encephalopathy. The age of last follow-up ranged from 3 years and 2 months to 7 years and 2 months. All 6 patients still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset of patients with IQSEC2 gene variants usually begins after 1 year of age. The common seizure types include epileptic spasms and focal seizures. Patients usually have a global developmental delay before seizure onset. IQSEC2 variants could be related to developmental and epileptic encephalopathy, and most patients are diagnosed with late onset infantile spasms. Epilepsy associated with IQSEC2 gene variants is usually refractory.
Female ; Male ; Child ; Humans ; Spasms, Infantile/genetics* ; Genotype ; Phenotype ; Epilepsy/genetics* ; Seizures ; Spasm ; Guanine Nucleotide Exchange Factors

ObjectiveTo investigate the role of PI3K/Akt/eNOS signaling pathway in the protective effect of hydrogen sulfide（H₂S） on endothelial cell senescence induced by hydrogen peroxide （H₂O₂）. MethodsSenescence in human umbilical vein endothelial cells （HUVEC） was induced by 60 μmol/L H₂O₂ for 1 h， and the effects of NaHS on the senescence were examined by the expression of plasminogen activator inhibitor 1 （PAI-1） and senescence-associated β-galactosidase （SA-β-Gal） staining. Meanwhile，the expression of protein kinase B（Akt）， Phospho protein kinase B（p-Akt）， and endothelial nitric oxide synthase （eNOS） were examined by western blot， and the senescence-related parameters. The content of the nitric oxide （NO） was measured by nitrate reduction method. ResultsCompared with the control group， after being treated with 60 μmol/L H₂O₂， the number of SA-β-gal positive cells and the expression of PAI-1 were significantly increased. However， after pretreatment of NaHS， the expression of PAI-1， the ratio of SA-β-gal positive cells was significantly decreased， but the expression of p-Akt， eNOS and the NO concentration increased. ConclusionNaHS could reverse HUVEC senescence induced by H₂O₂， and this may be highly associated with PI3K/Akt/eNOS signaling pathway.

Objectives Anticardiolipin antibody (aCL) is an important component of antiphospholipid antibody (aPL) and a marker antibody of antiphospholipid syndrome (aPS). APL is positive in 20% to 40% of patients with systemic lupus erythematosus(SLE). This article investigated the clinical features and prognosis of SLE patients with aCL. Methods From January 1999 to December 2009, 495 cases of SLE patients detected aCL who were hospitalized for the first time in 26 hospitals in Jiangsu Province including Nanjing Drum Tower Hospital were divided into aCL-positive group and aCL-negative group according to the test results. The patients were followed up in survival status, and the demographic characteristics, affected organs, laboratory tests, treatment drugs, and prognosis were compared between two groups. Results 146 of the SLE patients in this group were positive for aCL. The proportion of women in aCL- positive group (96.6%) was significantly higher than that in aCL-negative group (90.8%), and the difference was statistically significant (P<0.05). The proportion of anemia (74.7% vs 61.3%), decreased C3(81.5% vs 71.1%), positive antinuclear antibody(97.2% vs 92.4%), and positive anti-dsDNA antibody (61.9% vs 49.6%) in aCL-positive group were significantly higher than those of aCL-negative group, and the difference was statistically significant (P<0.05). The aCL-positive group received a higher proportion of cyclophosphamide immunosuppressive therapy (39.5% vs 50.7%, P<0.05). At the end of follow-up, the mortality rate of aCL-positive group was 13.7%, and the mortality rate of aCL-negative group was 14.9% and there was no significant difference in mortality (P>0.05). Kaplan-Meier survival analysis showed that the 1-year, 5-year, and 10-year survival rates of aCL-positive group were 94.5%, 89.0%, and 82.9%, respectively, and there was no significant difference compared with aCL-negative group(P=0.776). The main causes of death in aCL-positive group were lupus encephalopathy (6 cases, 30.0%), renal failure (5 cases, 25.0%), heart failure (4 cases, 20.0%) and infection (3 cases, 15%). The main causes of death in aCL-negative group were infection (21 cases, 40.4%), lupus encephalopathy (11 cases, 21.2%) and heart failure (5 cases, 9.6%) and renal failure (4 cases, 7.7%). Conclusion SLE patients with aCL represent a high propotion in anemia, decreased C3, positive antinuclear antibody, positive anti-dsDNA antibody. There was no significant difference in disease activity and significant organ involvement between two groups. More SLE patients with aCL were treated with cyclophosphamide, and there was no significant difference in survival status between SLE patients with and without aCL during long-term follow-up.

Objective To explore the relationship between the expression of decoy receptor 3 (DcR3) and high-risk human papilloma virus(HR-HPV)infection in cervical carcinoma. Methods Immunohistochemistry and hybird capture Ⅱ assay were used to detect the expression of DcR3 and HR-HPV in 35 cases of normal cervical tissues(NCE), 39 cases of cervical intraepithelial neoplasm(CIN)and 44 cases of cervical squamous epithelial carcinoma(CSES). Specific HR-HPV16 E7 siRNA and nonspecific HR-HPV16 E7 siRNA were synthesized and transfected to SiHa cells by Lipofectamine. The expression of DcR3 at mRNA and protein levels was examined by real-time polymerase chain reaction and western blot. The growth inhibition was examined by MTT assay. Results In NCE, CIN and CSES, the positive expression rates of DcR3 were 8.6%(3/35), 48.7%(19/39)and 77.3%(34/44), respectively, and the expression intensity was increasing(2=36.942, P<0.001). In NCE, CIN and CSES, the infection rates of HR-HPV were 5.7%(2/35), 56.4%(22/39)and 93.2%(41/44), respectively(2=60.322, P<0.001) . The protein expression of DcR3 was positively correlated with the infection of HR-HPV in CSES(r=0.893, P=0.004). Conclusions DcR3 was highly expressed in cervical cancer. Its expression was positively correlated with HR-HPV infection, which may contribute to the occurrence and development of cervical cancer. HR-HPV silencing inhibited cellular growth and proliferation by down-regulating the expression of DcR3.

Objective:To investigate the immunomodulation of CCK8 on the Coxsackievirus B ( CVB )-attacked human peripheral blood plasmacytoid dendritic cells(pDC). Methods:Peripheral blood mononuclear cells of healthy volunteers were separated by Ficoll-Hypaque gradient density centrifugation. The pDC was separated and divided into five groups,which were the control group, CVB attacked group,the group of CCK8 treated after CVB attack,the group of PGE2 treated after CVB attack and the group of CCK8+PGE2 treated after CVB attack. 100-time TCID50 of CVB was applied for the attack on pDC. Real-time PCR and Immunofluorescence technique were employed to detect the expression of CCK1R/CCK2R mRNA and protein. Then,the expression levels of costimulatory molecules such as CD80,CD86,HLA-DR ligand,and the chemokine receptor CCR7 were evaluated by Flow Cytometry Analysis. The supernatants of pDCs were collected, and the content of IFN-α was determined by Enzyme-linked Immunosorbent Assay. Results:CCK1R and CCK2R were co-expressed in human peripheral blood pDC,and both were significantly upregulated after CVB attack in vitro. Expression of CD80,CD86,HLA-DR and IFN-α were decreased in the CVB+CCK8 group compared with the CVB group,which suggested that CCK8 may reduce the CVB activation of pDC. Whereas expression of CD80,CD86,HLA-DR,CCR7 and IFN-α were increased in the CVB+PGE2 group compared with the CVB group,which suggested that PGE2 may increase the CVB activation of pDC in vitro. Conclusion:CCK8 repressed the CVB-attacked pDC,while PGE2 activated the CVB-attacked pDC.

Objective To observe the clinical efficacy of acupoint injection at Fenglong (ST 40) with Promethazine in treating posterior circulation ischemic vertigo (PCIV) due to turbid phlegm obstructing the middle.Method Sixty-two patients with PCIV due to turbid phlegm obstructing the middle were randomized into a treatment group and a control group, 31 cases each. The two groups both received intravenous infusion of Vinpocetine injection, based on which, the treatment group was intervened by injection at Fenglong (ST 40) with Promethazine, while the control group was given gluteal intramuscular injection of Promethazine. The traditional Chinese medicine (TCM) syndrome score and Dizziness Handicap Inventory (DHI) were observed for the two groups before and after the treatment, and the clinical efficacies were also compared.Result The TCM syndrome and DHI scores were significant changed after the intervention in both groups (P<0.05). After the treatment, the TCM syndrome and DHI scores in the treatment group were significantly different from those in the control group (P<0.05). The total effective rate was 93.5％ in the treatment group versus 80.6％ in the control group, and the between-group difference was statistically significant (P<0.05).Conclusion Injection at Fenglong (ST 40) with Promethazine is an effective method in treating PCIV due to turbid phlegm obstructing the middle.

Objective To investigate the reliability of MRI classification and clinical significance of deep gray matter injury(DGMI)in children with cerebral palsy(CP).Methods We made a retrospective assessment of 14 children with gross motor function classification system(GMFCS),manual ability classification system(MACS)and MRI classification system of deep gray matter injury.Based on T2WI,two radiologists worked independently and graded MRI pictures according to three-grading system and four-grading system.To evaluate the reliability of different grading systems,intra-observer and inter-observer agreements were tested by Kappa test.Spearman correlation analysis was performed to analyze the MRI classification system with GMFCS and MACS.Results The Kappa value of the intro-observer and inter-observe agreement of three-grading system was 0.873 and 0.873,respectively (P＜0.001).The Kappa value of the intro-observer and inter-observe agreement of four-grading system was 0.901 and 0.611(P＜0.001).Three-grading system had no significant correlation with GMFCS(r=0.053,P＞0.05)or MACS(r=0.128,P＞0.05).Four-grading system had a significant positive correlation with GMFCS(r=0.605, P＜0.05)and MACS(r=0.779,P＜0.05).Conclusion In the two grading systems,four-grading system is a more repeatable approach for detecting deep gray matter,gross motor function and manual function injuries in children with cerebral palsy.

SUMOylation is a dynamically reversible process that needs to be modified by a specific ligase, while its inverse reaction deSUMOylation is catalyzed by a group of SUMO-specific proteases (SENPs). SUMO-modified target protein molecules are closely related to development and disease, especially tumor, metabolism, inflammation and immunity. SENPs play an important role in SUMO protein maturation and deSUMOylation. This review discussed the functions of SENPs in the development and progression of tumors and related mechanisms.

OBJECTIVETo investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms.

METHODSLSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry.

RESULTSThe killing rate of allo-NK cells to LSC treated with 10 µmol/L decitabine for 24 hours was significant higher than that to LSC without treatment(60.52%±3.52% vs 22.08%±2.07%, 73.93%±2.33% vs 28. 99%±3.13%, 83.08%±1.32% vs 36.44%±2.40%, respectively)at the effector-target ratios of 5:1, 10:1, 20:1 (P<0.05). At the effector-target ratio of 10:1, decitabine significantly enhanced the apoptosis of LSC induced by allo-NK cells (7.84%±0.34% vs 3.33%±0.64%)(P<0.05). The expressions of NKG2D ligands(MICA/B,ULBP1,ULBP2,ULBP3) on LSC treated with decitabine 10 µmol/L for 24 hours were significantly increased (P<0.05).

CONCLUSIONDecitabine may enhance the allo-NK cell-mediated killing effects on LSC by up-regulation of the expressions of NKG2D ligands on LSC.