Gastric mucosal precancerous lesions in Helicobacter pylori-infected pediatric patients in central China: A single-center, retrospective investigation.

BACKGROUND: Helicobacter pylori (H. pylori) infects about 50% of the world population and is the major cause of chronic gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection induces gastric mucosal precancerous lesions mostly in adulthood, and it is debatable whether these pathological conditions can occur in childhood and adolescents as well. Since this is a critical issue to determine if intervention should be offered for this population group, we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H. pylori and gastric cancer. AIM: To investigate the relationship of H. pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China. METHODS: We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients with H. pylori infection and endoscopic and histological data. H. pylori infection status was determined by rapid urease test and histopathological examination. Both clinical and pathological data were collected and analyzed retrospectively. Occurrence of gastric mucosal precancerous lesions, inflammatory activity and degree of inflammatory cell infiltration between H. pylori-positive and -negative groups were compared. RESULTS: Among the 1015 eligible children and adolescents, the overall H. pylori infection rate was 84.14% (854/1015). The infection rate increased with age. The incidence of gastric mucosal precancerous lesions in H. pylori-infected children was 4.33% (37/854), which included atrophic gastritis (17 cases), intestinal metaplasia (11 cases) and dysplasia (9 cases). In H. pylori-negative patients, only 1 atrophic gastritis case [0.62%, (1/161)] was found (P < 0.05). Active inflammation in H. pylori-infected patients was significantly higher than that in non-infected patients, and the H. pylori-infected group showed more severe lymphocyte and neutrophil granulocyte infiltration (P < 0.001). In addition, endoscopy revealed that the most common findings in H. pylori-positive patients were antral nodularity, but in H. pylori-negative patients only superficial gastritis was observed. CONCLUSION: In children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of H. pylori-infected patients in central China. These cases included atrophic gastritis, intestinal metaplasia, and dysplasia. The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

Both family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are cost-effective for gastric cancer prevention.

BACKGROUND: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family-based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost-effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost-effectiveness of FBCM, screen-and-treat, and no-screen strategies in Chinese population. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model. RESULTS: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen-and-treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer-related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no-screen strategy. Cost-effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen-and-treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no-screen strategy. One-way sensitivity analysis revealed that screening from younger age by both strategies are more cost-effective. When compared with FBCM strategy, screen-and-treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results. CONCLUSIONS: Both FBCM and screen-and-treat strategies are cost-effective for gastric cancer prevention compared with no-screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost-effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas.

Establishment of a Lung Cancer Discriminative Model Based on an Optimized Support Vector Machine Algorithm and Study of Key Targets of Wogonin in Lung Cancer.

An optimized support vector machine model was used to construct a lung cancer diagnosis model based on serological indicators, and a molecular regulation model of Wogonin, a component of Scutellaria baicalensis, was established. Serological indexes of patients were collected, the grid search method was used to identify the optimal penalty coefficient C and parameter g of the support vector machine model, and the benign and malignant auxiliary diagnosis model of isolated pulmonary nodules based on serological indicators was established. The regulatory network and key targets of Wogonin in lung cancer were analyzed by network pharmacology, and key targets were detected by western blot. The relationship between serological susceptibility genes and key targets of Wogonin was established, and the signaling pathway of Wogonin regulating lung cancer was constructed. After support vector machine parameter optimization (C = 90.597, g = 32), the accuracy of the model was 90.8333%, with nine false positives and two false negative cases. Ontology functional analysis of 67 common genes between Wogonin targets and lung cancer-related genes showed that the targets were associated with biological processes involved in peptidye-serine modification and regulation of protein kinase B signaling; cell components in the membrane raft and chromosomal region; and molecular function in protein serine/threonine kinase activity and heme binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that the regulation pathways involved the PI3K-Akt signaling pathway, ERBB signaling pathway, and EGFR tyrosine kinase inhibitor resistance. In vitro analyses using lung cancer cells showed that Wogonin led to significantly increased levels of cleaved caspase-3 and Bad and significantly decreased Bcl-2 expression in a concentration-dependent manner. ErbB4 expression also significantly decreased in lung cancer cells after treatment with Wogonin. A regulatory network of Wogonin regulating lung cancer cell apoptosis was constructed, including the participation of serological susceptibility genes. There is a certain regulatory effect between the serological indexes that can be used in the diagnosis of lung cancer and the key targets of Chinese herbal medicine treatment of lung cancer, which provides a new idea for the diagnosis, treatment and prognosis of clinical lung cancer.

Cloning, expression and enzyme activity delineation of two novel CANT1 mutations: the disappearance of dimerization may indicate the change of protein conformation and even function.

BACKGROUND: Desbuquois dysplasia (DBQD) was a rare autosomal recessive skeletal dysplasia. Calcium activated nucleotidase 1 (CANT1) mutation was identified as a common pathogenic change for DBQD type 1 and Kim variant but not for DBQD type 2. To our knowledge, all patients with DBQD type 1 currently found could be explained by mutations in the CANT1 gene, but mutations in the CANT1 gene might not be directly diagnosed as DBQD type 1. RESULTS: We have identified two novel CANT1 mutations (mut1: c.594G > A [p.Trp198*], mut2: c.734C > T [p.Pro245Leu]) in three children from a family of Chinese origin for the first time. Two of the three children could be diagnosed as typical DBQD type 1 and one child could not be diagnosed as DBQD type 1 based on the clinical data we had. To further clarify the effect of the two mutations of the CANT1 gene, we studied the CANT1 gene expression and detected the protein secretion and nucleotide enzyme activity through cDNA cloning and expression vectors construction for wild and mutant types. The mut1 was a nonsense mutation which could lead to premature termination and produced the truncated bodies; The CANT1 dimer of mut2 was significantly reduced and even undetectable. The extracellular secretion of mut1 was extremely high while mut2 was significantly reduced compared with the wild type. And mut1 and mut2 also could result in a significant reduction in the activity of CANT1 nucleotidease. From the results we could deduce that the two mutations of the CANT1 gene were the causes of the two cases in this study. CONCLUSIONS: Regarding the particularity of the cases reported in this study, the pathogenesis of CANT1 might be more complicated. The genetic and phenotype of three children with the same genetic background need to be further studied. Larger cohort of patients was needed to establish genotype-phenotype correlations in DBQD.

Effect of TRPV1 gene mutation on bronchial asthma in children before and after treatment.

Bronchial asthma is a worldwide disease with high incidence. It not only harms children's physical and mental health, but it also brings a heavy burden to their families as well as the society. However, the trigger and pathogenesis of the disease remain unclear. This study aimed to analyze TRPV1 gene mutation and expression of cytokines in children with acute bronchial asthma before and after treatment, thus providing theoretical guidance for the diagnosis and treatment of bronchial asthma in children. Real-time quantitative polymerase chain reaction was adopted to detect TRPV1 mRNA expression level and enzyme-linked immuno sorbent assay was used to detect the serum total IgE level, eosinophil (EOS) number, IL-4, IL-5, and interferon (IFN) gamma levels in peripheral venous blood of children in the healthy control group and asthma group before and after treatment. Logistic regression analysis was applied to analyze the most essential factor inducing bronchial asthma in children. TRPV1 mRNA level of peripheral blood in the asthma group was higher than that in the control group before treatment (p < 0.01). The IL-4, IL-5, and EOS levels in serum were markedly higher than those in the control group (p < 0.01), whereas the IFN-gamma level was lower than that in the control group (p < 0.01). After conventional treatment, TRPV1 mRNA level increased significantly (p < 0.01). The levels of serum IL-4, IL-5, and EOS were significantly lower than those before treatment (p < 0.01), whereas, IFN-gamma level was higher than that before treatment (p < 0.01). Compared with that before treatment, the expression level of IgE showed a significant decrease after treatment (p < 0.01). The results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level, and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children. TRPV1 gene mutation was closely related to bronchial asthma in children, which provided a theoretical basis for the treatment and prognosis of children with bronchial asthma.

Preliminary study on pathogenesis of bronchial asthma in children.

BACKGROUND: The etiology and pathogenesis of bronchial asthma remain unclear. This study is to investigate the risk factors related to bronchial asthma onset in children from genetics and immunology and preliminarily reveal the pathogenesis of bronchial asthma in children. METHODS: Real-time quantitative PCR was adopted to detect the expression level of TRPV1 gene and mRNA and enzyme-linked immunosorbent assay method to the total immunoglobulin E level and levels of IL-4, IL-5, and IFN-γ in serum in peripheral venous blood for children in two groups. Logistic regression analysis was applied to analyze the most essential factors inducing bronchial asthma in children. RESULTS: The mRNA level of TRPV1 in peripheral blood in the case group was higher than that in the control group (P < 0.01). The levels of IL-4, IL-5, and eosinophils in serum in the case group were markedly higher than those in the control group (P < 0.01), while IFN-γ level in the case group was lower than that in the control group (P < 0.01). The results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level, and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children. CONCLUSION: The levels of TRPV1 gene expression and Th1/Th2 cytokines have a close relationship with asthma onset in children, which provides theoretical evidences for molecular targeted treatment in children with bronchial asthma.