Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

Venous thromboembolism(VTE)is a prevalent complication in orthopedics.In recent years,machine learning has been widely applied in orthopedics.The essence of machine learning lies in utilizing algorithms to analyze vast amounts of data and construct risk prediction models that can accurately forecast unknown clinical outcomes.By integrating high-risk factors,machine learning aids medical professionals in precisely identifying and screening individuals with a high risk of VTE and offering them timely individualized interventions.This article reviews the concept and classification of machine learning,the advantages of machine learning in enhancing model prediction ability,and the current application status of machine learning in constructing risk prediction models for patients with VTE.

Objective:To systematically evaluate the role of air pollutants in the development and exacerbation of autoimmune rheumatic diseases.Methods:We followed PRISMA guidelines and searched EMBASE, Scopus, PubMed, and Cochrane Library databases using keywords and MeSH terms from inception to July 2019. Observational studies reporting the relationship between autoimmune rheumatic diseases and exposure to certain air pollutants were included. Screening of literature according to established inclusion and exclusion criteria. No meta-analysis but the qualitative analysis was conducted due to the high methodological heterogeneity.Results:A total of 24 studies were included. Rheumatoid arthritis (RA) ( n=6), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) ( n=1), ankylosing spondylitis (AS) ( n=1), systemic lupus erythematosus (SLE) ( n=3), childhood-onset systemic lupus erythematosus (cSLE) ( n=3), juvenile idiopathic arthritis (JIA) ( n=2), Kawasaki disease (KD) ( n=4), systemic autoimmune rheumatic diseases (SARD) ( n=4). The results of the study suggested that short-term elevation in particulate matter (PM)2.5 concentration was possibly associated with an increased risk of SLE and cSLE flare-ups, disease activity of AS, JIA and SARDs exacerbation. Studies demonstrated an increased risk of RA with cumulative exposure to carbon monoxide (CO), nitrogen dioxide (NO 2), ozone (O 3), and sulfur dioxide (SO 2). Only one study demonstrated an increased risk of KD admission with elevated O 3 levels. No association was found between AAV and ambient air pollution. Conclusion:Air pollution is likely to be involved in the development and exacerbation of certain autoimmune diseases. At the same time, the mechanism of autoimmune diseases of ambient air pollutants should be actively studied, so as to promote the early prevention of cardiovascular diseases.

In recent years, the issue of end-of-life decision making has received broad attention. More and more people have been appealing for the respect for terminal patients’ wishes in decision making. Many scholars have proposed the application of advance medical decision to ensure the autonomy of terminally ill patients. Given that advance medical decision does not have legal effect in China, the Beijing Health Law Society proposed the "Expert Consensus on Legal Issues Related to End-of-life Decision Making" in July 2022. This consensus provides clear guidance on how to make medical decisions for terminally ill patients, based on the principle of respecting the patient’s wishes within the framework of current laws and regulations. The consensus aims to provide guidance for both doctors and patients about how to respect patients’ own wishes and protect their autonomy, as well as to provide reference for future law and policy formulation on related issues.

Objective:To investigate the clinical manifestation, genetic characteristics, treatment and prognosis of Crouzon-like syndrome.Methods:Clinical data of one case of Crouzon-like syndrome diagnosed in Children′s Hospital Affiliated to Zhengzhou University in May 2019 were collected, including clinical test, treatment plan, follow-up outcomes. The clinical characteristics and the mutation characteristics of IL11RA-related Crouzon-like syndrome were analyzed combined with the literature.Results:The male proband, five years and four months old, was admitted with the main clinical manifestations including headache, vomiting, exophthalmos, ocular hypertelorism, nasal root flat and scaphocephaly. CT showed that the cerebellar tonsil moved down slightly, the occipital magnum was full, the bilateral cranial plates were locally thinner, the bilateral cranial diameters were increased, and the cranial seams were closed. Magnetic resonance imaging showed ChiariⅠmalformation. The mutation c.40_63del and splice site mutation c.811-2A>G of the patient′s IL11RA gene were screened by whole exome sequencing. Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.811-2A>G was derived from the patient′s mother, and the other one is de novo.Conclusions:The main clinical manifestations of Crouzon-like syndrome are craniosynostosis and midface hypoplasia and ocular deformity. The study identified two novel mutations in the Crouzon-like syndrome related IL11RA gene. Genetic sequencing is helpful for accurate diagnosis and timely surgical treatment.

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ² test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues (P<0.05). KLK7 expression was correlated with vascular invasion(χ²=7.535, P<0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ²=7.535, P<0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group (t=4.479, P<0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group(t=2.831, P<0.05). Conclusions The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.

Objective: To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism. Methods: The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion. Establish a nude mice subcutaneously transplanted tumor model, 4 weeks after vaccination for tumor volume and weight measurement.Student t-test, rank sum test, and χ² test was used respectively to compare the data between two groups. Cox regression was adopted to improve the single factor and multiple factors analysis. Results: The results of hybridization in situ showed the expression of miR-1178 was increased in 72 cases with pancreatic cancer compared to that in paired normal pancreatic tissues (50/72 vs. 11/72, χ²=43.26, P<0.05). miR-1178 expression was positively associated with tumor lymph node stage (χ²=4.189, P=0.041). Univariate and multivariate analysis revealed that miR-1178 was an independent adverse prognostic indicator for patients with pancreatic cancer (HR=2.364, 95%CI: 1.114-5.019, P=0.025). Transwell assay indicated the over-expression of miR-1178 increased the number of AsPC-1 cells that penetrated the ECM-coated membrane (177.0±19.8 vs. 119.7±15.9)(χ²=8.21, P<0.05). For the in vivo experiment, overexpression of miR-1178 significantly promoted tumor growth, compared with control group (tumor volume: (5 122.4±760.2)mm³ vs. (1 976.8±601.8)mm³, t=2.413, P<0.05; tumor weight: (1.55±0.21)g vs. (0.67±0.17)g, t=2.960, P<0.05). Over-expression of miR-1178 down-regulated the expression of Stub1 and elevated the expression of FAK/MMP-9 signal pathway(P<0.05). Conclusions MiR-1178 is overexpressed in pancreatic cancer, and is effective for predicting patients′ prognosis. MiR-1178 regulate Stub1/FAK/MMP-9 signal pathway and promote the invasion of AsPC-1 cells.