ABSTRACT
BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
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Humans , Lung Neoplasms/genetics , Adenocarcinoma of Lung/genetics , China , Prognosis , Transcription FactorsABSTRACT
Objective:To compare the effects between electroacupuncture (EA) at Chize (LU 5, the He-Sea point of the Lung Meridian) and Shangjuxu (ST 37, the lower He-Sea point of the large intestine) in rats with ulcerative colitis (UC) on the variations of mesenteric microcirculation and vasoactive intestinal peptide (VIP) in the colon, lung, and hypothalamus. The relative specificity of acupoints was also explored. Methods: A total of 28 male Wistar rats were randomized into a normal group, a model group, a Chize (LU 5) group and a Shangjuxu (ST 37) group, 7 rats in each group. The UC model was established by enema with acetic acid. Since the third day after modeling, rats in the Chize (LU 5) group and Shangjuxu (ST 37) group respectively received EA at Chize (LU 5) and Shangjuxu (ST 37), 15 min each time for successive 7 d. The variations of mesenteric microvascular calibers and blood flow status were observed by a microcirculation microscopic tester; VIP in the colon, lung and hypothalamus was measured by radioimmunoassay. Results:Compared with the normal group, the mesenteric microvascular calibers were significantly expanded in the model group (P0.05); compared with the model group and Chize (LU 5) group, the calibers were obviously shrunk in Shangjuxu (ST 37) group (P0.05). The colonic VIP levels in the model group and Chize (LU 5) group were significantly higher than that in the normal group (P0.05). Conclusion:The effects of Chize (LU 5) and Shangjuxu (ST 37) were different in treating UC. Shangjuxu (ST 37) showed a more significant efficacy in down-regulating VIP in the colon and regulating mesenteric microcirculation, while the effects of Chize (LU 5) were not obvious.
ABSTRACT
Objective To evaluate high resolution manometry in the diagnosis of hiatal hernia.Methods Clinical data were reviewed on 20 patients suffering from gastroesophageal reflux who had laparoscopic Toupet fundoplication for preoperative tentative diagnosis of hiatal hernia.Preoperative diagnosis of hiatal hernia was made collectively by endoscopy,X-ray examination,24 hour esophageal pH monitoring and high resolution manometry before surgery.Results Preoperative diagnosis of hiatal hernia was made in 3 patients by X-ray examination,in 9 patients by high resolution manometry.11 patients were finally diagnosed with hiatat hernia intraoperatively.X ray was consistent with intraoperative diagnosis in 27％ cases.Intraoperative and endoscopic diagnoses were 55％.High resolution manometry and intraoperative diagnoses were consistent in 82％.Lower esophageal sphincter length was (1.92 ± 0.38) cm in hiatal hernia group and (2.10 ± 0.92) cm in non-hiatal hernia group (t =0.60,P ＞ 0.05),lower esophageal sphincter pressure (respiratory min) was (0.64 ±0.55) kPa in hiatal hernia group and (1.31 ± 1.07) kPa in nonhiatal hernia group(t =1.80,P ＞ 0.05),and lower esophageal sphincter pressure (respiratory mean) was (1.43 ±0.92) kPa in hiatal hernia group and (2.57 ± 1.33) kPa in non-hiatal hernia group(t =2.26,P ＜0.05).The reflux parameters,including the percent total time pH ＜ 4,and DeMeester score,were significantly greater in hiatal hernia group than in non-hiatal hernia group (all P ＜ 0.05).Conclusions Hiatal hernia patients are with poor esophageal antireflux competency and severe reflux.High resolution manometry is more valuable in the diagnosis of hiatal hernia than endoscopy or X-ray examination.