Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.

Objective To investigate the application value of extracellular volume fraction(ECV)obtained from enhanced CT in diagnosis and classification of acute pancreatitis.Methods The clinical data from patients with acute pancreatitis(acute pancreatitis group)and normal controls(control group)underwent enhanced CT were analyzed retrospectively.The CT values of pancreas and abdominal aorta in the same sclice on precontrast and equilibrium-phase images were measured,and then pancreatic ECV was calcu-lated.The measured parameters were compared between the groups of control and acute pancreatitis,and subgroups of non-severe and severe pancreatitis.The logistic regression analysis was used to identify the risk factors for acute pancreatitis and severe pancrea-titis,and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency in diagnosis and classifica-tion of acute pancreatitis.Results The pancreatic CT value and ECV were independent risk factors for acute pancreatitis(P＜0.05),and the ECV was an independent risk factor for severe pancreatitis(P＜0.05).The area under the curve(AUC)of ECV was higher in acute pancreatitis group(0.81)and severe pancreatitis subgroup(0.68).Conclusion As a quantitative parameter,the ECV obtained from enhanced CT has higher clinical application value and higher popularity in the diagnosis and classification of acute pancreatitis.

Sepsis is an important factor for trauma related death, especially the refractory septic shock, which has a mortality rate exceeding 50%. The treatment of sepsis is a medical problem that needs to be solved urgently. The role and status of extracorporeal membrane oxygenation (ECMO) in the treatment of cardiopulmonary failure has become more and more prominent, and its role in the treatment of sepsis in children and infants has gained remarkable achievements. However, its role in adult sepsis remains controversial, with current reports showing varied outcomes for ECMO in adult sepsis treatment. ECMO application can potentially cause renal impairment, and renal impairment can affect the outcomes of ECMO treatment in turn. Studies have shown that adjunctive renal replacement therapy during non-ECMO treatment of septic shock can improve the prognosis, and whether the combination with renal replacement therapy in the early stage of ECMO treatment can effectively improve the treatment outcome still needs to be confirmed by multicenter and prospective studies. Based on this, this article reviews the relevant research on the application of ECMO combined with renal replacement therapy in the treatment of sepsis after war trauma, aiming to provide clinical reference for the treatment of sepsis after war trauma.

Objective: Previous research has explored a variety of mental disorders associated with Internet Gaming Disoder (IGD) and Social Media Addiction (SMA). To date, few studies focused on the network characteristics and investigated mood and sleep symptoms across SMA and IGD of adolescence at a group-specific level. This study aims to identify different characteristics of IGD and SMA and further determine the group-specific psychopathology process among adolescents. Methods: We conducted a cross-sectional study to recruit a cohort of 7,246 adolescents who were scored passing the cutoff point of Internet Gaming Disorder Scale-Short Form and Bergen Social Media Addiction Scale, as grouped in IGD and SMA, or otherwise into the control group. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item, and Pittsburgh Sleep Quality Index were assessed for the current study, and all assessed items were investigated using network analysis. Results: Based on the analytical procedure, the participants were divided into three groups, the IGD group (n=789), SMA group (n=713) and control group (n=5,744). The edge weight bootstrapping analysis shows that different groups of networks reach certain accuracy, and the network structures of the three groups are statistically different (pcontrol-IGD=0.004, pcontrol-SMA<0.001, pIGD-SMA<0.001). The core symptom of SMA is “feeling down, depressed, or hopeless”, while IGD is “feeling tired or having little energy”. Conclusion Although IGD and SMA are both subtypes of internet addiction, the psychopathology processes of IGD and SMA are different. When dealing with IGD and SMA, different symptoms should be addressed.

ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay （DD）. MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered， Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration， and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed， and Chi square test was used to compare the age distribution differences in gross motor， fine motor， language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43％. A decreasing trend of DD rate in the 0‒ age group was observed （χ²=14.135， P<0.001）， while an increasing trend of DD rate in the 1‒ and <3 age groups was observed （χ²=5.375， P=0.020； χ²=5.558， P=0.018）. The DD rate of children aged 0‒2 years with Beijing household registration was higher （χ²=12.504， P<0.001）. The DD rate of gross motor was the highest in the 0‒ age group （64.60%）， the DD rate of language was the highest in the <3 age group （85.97%）， and a statistically significant difference of gross motor and language was separately found in the three age groups （χ²=183.061， P<0.001； χ²=78.450， P<0.001）. ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2， and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.

Objective:To analyze the clinical phenotype and genotype characteristics of children with pyridoxine-dependent epilepsy (PDE) and provide evidence for diagnosis.Methods:Clinical data of 3 children with PDE enrolled in the Department of Neurology of Hunan Children′s Hospital from July 2016 to December 2020 were collected, and whole-exome sequencing (WES) was used for analysis. Pathogenic variants were analyzed and screened using bioinformatics tools combined with clinical phenotype. Sanger sequencing was used to analyze the source of mutations in children′s core family members.Results:Cases 1 (female) and 2 (male) were siblings, both of whom had convulsions within 24 hours after birth. WES results showed that the siblings carried compound heterozygous mutations of c.796C>T (p.R266 *) and c.1553G>C (p.R518T) in the ALDH7A1 gene, coming from the father and mother of the siblings respectively. Both of the mutations have been reported as pathogenic. Case 3, female, developed convulsions at the age of 1. WES results revealed that she carried compound heterozygous mutations of c.1094-109T>A and c.7C>T (p.R3C) in the ALDH7A1 gene, coming from her father and mother respectively. After searching HGMDPro, PubMed, 1000 Genomes, and dbSNP databases, both of the 2 mutations of c.1094-109T>A and c.7C>T (p.R3C) were not reported. The pathogenicity predictions of the 2 mutations were carried out by different biological information analysis software. The results showed that both of the mutations were harmful. All the 3 children had no epileptic seizures after treatment with increased doses of vitamin B6. Conclusions:When infants have unexplained convulsions, especially in the neonatal stage, PDE caused by ALDH7A1 gene mutation should be considered. Pyridoxine precision treatment has a good effect. The 2 de novo mutations of c.1094-109T>A and c.7C>T (p.R3C) enrich the mutation spectrum in the ALDH7A1 gene. WES has the auxiliary significance in the diagnosis of epilepsy.

Objective : To investigate the effects of dihydroartemisinin ( DHA) on cell growth , migration invasion and vasculogenic mimicry ability of non⁃small cell lung cancer ( NSCLC) . Methods : Different concentrations of DHA were added to NSCLC cell lines A549 and H3255 , and after 24 hours , the cell viability was detected by CCK8 method , and the migration and invasion ability of NSCLC cells was detected by Transwell experiment . qRT⁃PCR and Western blot detected E ⁃cadherin , N ⁃cadherin , and Vimentin mRNA and protein expression levels , respectively .Three⁃dimensional cell was cultured to observe the vascular⁃like morphological generation of cells . qRT⁃PCR and Western blot detected human vascular endothelial cadherin (VE⁃cadherin) mRNA and protein expression levels as marker of vasculogenic mimicry . Results : DHA inhibited cell growth of A549 and H3255 and showed time⁃dependent and concentration⁃dependent . DHA inhibits the invasion and metastasis ( all P < 0. 001) of A549 and H325 cells ; DHA upregulated the expression of E ⁃Cadherin at mRNA(all P < 0. 001) and protein(P < 0. 001;P < 0. 01) levels in A549 and H3255 cells , and downregulated the expression of N ⁃cadherin at mRNA (all P < 0. 01) and protein (all P < 0. 001) levels as well as the expression of Vimentin at mRNA (P < 0. 01;P < 0. 001) and protein (all P < 0. 001) levels . The results of three⁃dimensional cell culture showed that the 12⁃hour vasculogenic mimicry generation capacity of DHA⁃treated A549 cells and H3255 cells was reduced , and the expressions of VE⁃cadherin at mRNA (P < 0. 001;P < 0. 01) and protein (all P < 0. 001) levels were downregulated . Conclusion Dihydroartemisinin inhibits the growth , migration invasion and vasculogenic mimicry ability of non⁃small cell lung cancer cells

Objective: To explore the correlation between epidermal growth factor receptor ( EGFR) mutation and brain metastasis in lung adenocarcinoma． Methods: Comparisons of brain metastasis between lung adenocarcinoma patients with EGFR exon 19 deletion ( 19 Del) and a single point mutation of L858R in exon 21 (21 L858R) at initial diagnosis and after EGFR-TKIs targeted therapy were analyzed．The CCK-8 assay was used to detect and calculate the semi-inhibitory concentration (IC50 ) of gefitinib against EGFR-mutated lung adenoma cell lines PC9 and H3255 . Results: Of the 410 patients with lung adenocarcinoma，a total of 153 (37. 3% ) cases had brain metastasis．Age，lymph node metastasis and 21 L858R mutation were high-risk factors for brain metastasis of lung adenocarcinoma．Among newly diagnosed 48 EGFR-mutated lung adenocarcinoma patients with brain metastasis ，the number of 19 Del and 21 L858R were 14 and 34，respectively (P = 0. 006) ．There were 17 patients with 19 Del and 20 patients with 21 L858R were observed to complicated by brain metastasis after receiving EGFR-TKIs targeted therapy．The median time of brain metastasis after EGFR-TKIs treatment were 15 months (8. 50，25. 00) and 7 months (4. 25，12. 25 ) ，respectively ( P = 0. 013 ) ． The IC50 of PC9 and H3255 to gefitinib were (0. 037 ± 0. 008) and (0. 150 ± 0. 040) μmol / L，respectively (P = 0. 007) ． Conclusion Age younger than or equal to 60 years，lymph node N2-3 stage，and EGFR 21 L858R mutation are high-risk factors for brain metastases in patients with lung adenocarcinoma，and the latter still has a shorter time to brain metastases than 19 Del mutations after treatment with EGFR-TKIs，which may be related to drug sensitivity.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM). METHODS: A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients. RESULTS: This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.
Humans ; Computational Biology ; Genetic Counseling ; Genomics ; Mutation ; Neurodevelopmental Disorders/genetics* ; Dyskinesias ; GTP-Binding Protein alpha Subunits, Gi-Go