Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

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.

Advances in the study on cytokines related to dental pulp regeneration / 口腔医学

@#With the development of molecular biology, biomaterials and tissue engineering, regenerative treatment of pulpal and periradicular diseases is facing new opportunities. At present, a large number of studies on dental pulp regeneration reveal that cytokines are essential for promoting migration, proliferation and osteogenic differentiation of dental pulp stem cells. In this paper, we review several kinds of cytokines related to dental pulp regeneration, and analyze their roles and regulatory mechanisms in dental pulp regeneration.

Clinical significance of neutrophil-to-lymphocyte ratio in assessing response to cardiac resynchronization therapy in elderly patients / 中华老年医学杂志

Objective To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR)in assessing response to cardiac resynchronization therapy(CRT)in elderly patients.Methods Clinical data of 105 elderly patients with chronic heart failure(CHF)who had received CRT at our hospital from January 2006 to January 2017 were retrospectively analyzed,and patients were divided into a no-response group(n=42)and a response group(n=63)according to CRT outcomes after 6 months.General clinical data were compared between the two groups.Factors influencing response to CRT were analyzed by logistic regression model analysis.The receiver-operating characteristic(ROC)curve was used to assess the predictive value of NLR in response to CRT.Results Compared with the response group,the no-response group had increased baseline levels of initial QRS width,serum creatinine(Scr) and uric acid(UA)(P ＜0.05).There was no significant difference in left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter (LVESD),the New York Heart Association (NYHA) functional classification,neutrophil count,lymphocyte count and NLR between the two groups before CRT(P＞0.05).After 6 months of CRT,the LVEDD,NYHA functional class,neutrophil count and NLR were higher,and LVEF and lymphocyte count were lower in the no-response group than in the response group(P ＜0.05).The difference in NLR between 6 months after CRT and before CRT(△NLR)was higher in the no-response group than in the response group(P ＜0.05).Multi-factor Cox regression analysis showed that NLR (OR =1.895,95％CI:1.538～5.284,P =0.031)and △NLR(OR =2.579,95％CI:2.110～8.329,P =0.005) were independent risk factors for CRT (HR =1.590,95 ％ CI:1.215 ～ 2.146,P =0.013).ROC curve analysis showed that ROCAUC of △NLR in the no-response group was 0.891,95％CI:0.832～0.937,which was higher than that at 6 months after CRT(0.813,95 ％ CI:0.765～0.864)(Z=2.712,P＜0.05).Conclusions The increase in NLR after CRT may be an early sign for noresponse to CRT,and dynamic monitoring of NLR should be promoted to assess the prognosis of patients undergoing CRT.

Retrospective evaluation of echocardiography in mechanical prosthesis valve dysfunction / 中华超声影像学杂志

Objective To evaluation the diagnostic value of echocardiography in mechanical prosthesis valve dysfunction(MPVD).Methods Fifty-two patients who underwent reoperation due to MPVD were included,and the preoperative,introperative and postoperative results of echocardiography was compared with the results of surgery or pathologic diagnosis.Results The etiology of MPVD based on cardiac surgery was thrombus in 12,fibrous tissue hyperplasia in 23,thrombus and fibrous tissue hyperplasia in 16,lost of mechanical disc in 1.The types of MPVD diagnosed by echocardiography were stenosis in 29,regurgitation in 2,stenosis and regrigitation in 12,intermittent obstruction in 8,and total obstruction in 1.Successful assessment of prosthetic disc by transthoracic echocardiography was 78.4％ and can be improved to 96.1 ％ when combined with transesophageal echocardiography.Complementary message by transesophageal echocardiography were provided in 10 patients and corrective message in 1 patient.No recurrent MPVD was find during the follow-up.Conclusions Echocardiography can be used as the frist choice for the evaluation of the MPVD and can make precise assessment of the abnormal hemodynamic change and state of motion of the valve.

Echocardiographic Characteristics for Diagnosing the Patients With Primary Non-mucinous Cardiac Tumor / 中国循环杂志

Objective: To explore the clinical, pathological and echocardiographic characteristics of rare primary non-mucinous cardiac tumor (PNCT) and to investigate the diagnostic value of echocardiography in benign and malignant PNCT with various pathological classiifcations. Methods: We retrospectively studied 32 PNCT patients including 21 benign and 11 malignant patients treated in our hospital from 2003-01 to 2013-02. There were 23 male and 9 female from 0.5 to 66 (36.92 ± 20.17) years of age. We analyzed the clinical information of echocardiography, CT, MRI and operation, and the ifndings were conifrmed by pathology. Results: Statistic analysis presented that there were more male PNCT patients than female, the ratio of male/female in benign patients was 16/5, in malignant patients was 7/4, P0.05, and either infant or adult could suffer from PNCT. Benign PNCT was more in left heart and malignant PNCT was more in right heart. Compared with benign PNCT, malignant lesions were usually no base, with irregular shape, pericardial effusion and surrounding tissue adhesion. Conclusion: Echocardiography was sensitive for diagnosing the patients with PNCT, it could preliminarily identify benign and malignant lesions with different ultrasonographic manifestation.

Application and observation of sedative drugs on uncooperative children in CT examination / 医疗卫生装备

Objective To observe the effect of sedative drugs applied on uncooperative children in CT examination. Methods 204 samples were divided into groups of baby, infant and preschool children. 20 minutes before CT scan, chloral hydrate and diazepam were taken by those uncooperative children seperately. Drug dosage was calculated according to body weight (kg). Results The effective rate of chloral hydrate were 96.8%(30 cases) in baby group,54.2%(13 cases) in infant group and 53.9%(21eases) in preschool children group, while that of diazepam were 100%(9 cases), 82.6%(19 cases) and 87.2%(68 cases) respectively.Conclusion When approriate sedative drugs were taken by uncooperative children, satisfactory scanning images can be obtained in CT examination