The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis.

Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n = 30) and without (n = 30) ovarian endometriosis.Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p < .05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p < .05). Positive correlation was found between SHP2 and GAB2 in endometrium (p < .01). SHP2 and GAB2 both positively correlated with VEGF (p < .05), but not Ki67 in endometrium.Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.

Trends in prescription therapy for adolescents with depression in nine major areas of China during 2017-2021.

Objective: To date, no national-scale drug usage survey for adolescents with depression has been conducted in China, and the purpose of this study was to examine the national trends in prescriptions in Chinese adolescent depression patients from 2017 to 2021. Methods: Prescribing data were extracted from the Hospital Prescription Analysis Cooperative Project. The average number of patients per year, the cost of treatment, and the prescription patterns (monotherapy vs. combination therapy) were analyzed, and subgroup analyses were conducted depending on age, sex, and drug class. Results: The study included 674,099 patients from 136 hospitals located in nine major areas of China. Of all patients, the proportion of adolescents increased from 1.63% in 2017 to 6.75% in 2021. Visits by adolescent depression patients increased from 1,973 in 2017 to 9,751 in 2021, and the corresponding cost increased from 607,598 Chinese Yuan in 2017 to 2,228,884 Chinese Yuan in 2021. The incidence of adolescent depression among female individuals was far beyond that among male individuals. Combination therapy was more frequent than monotherapy, and the most commonly prescribed drugs were antidepressants, antipsychotics, antiepileptics, and antianxietics. Despite the use of sertraline decreasing from 47.90 to 43.39%, it was the most frequently used drug. Conclusion: In summary, the prescriptions and cost of treatment for adolescent depression patients both increased rapidly. The widespread use of those drugs with weak clinical evidence reflects the current state of China, which should arouse our attention. The study can provide references for clinical treatment decisions and a basis for more efficient allocation of healthcare resources by the government.