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Objective: Limited evidence suggests a vital role for SEC11A in carcinogenesis. Our study conducted an integrated analysis on the molecular features and clinical relevance of SEC11A across pan-cancer based on multi-omics data. Materials and Methods: SEC11A expression was analyzed in 33 types of tumor and normal specimens utilizing transcriptome profiles from TCGA-GTEx project and protromic data from CPTAC project. Copy number alterations and methylation of SEC11A were investigated across pan-cancer with cBioPortal. Clinical relevance and prognostic implications of SEC11A were evaluated in TCGA cohorts. GSEA of SEC11A was conducted in head and neck squamous cell carcinoma (HNSCC) with clusterProfiler package. Correlation of SEC11A with immune cell infiltrations was estimated with EPIC, TIMER, xCELL, MCP-counter, quanTIseq, CIBERSORT, and ImmuCellAI algorithms. IC50 values of anti-cancer agents were curated from GDSC project and their correlations to SEC11A were calculated. Results: We found the expression of SEC11A was upregulated in most of cancer types (24/33), while was downregulated in 3 types of cancers. Genetic amplification in SEC11A was widespread across pan-cancer. There were negative correlations of SEC11A RNA expression with methylation level. The upregulation of SEC11A indicated unfavorable prognosis in adrenocortical carcinoma and HNSCC. Moreover, SEC11A was closely involved in cell cycle, TP53 regulation and antigen processing. SEC11A was positively associated with tumor-associated macrophage and fibroblast but negatively associated with CD8+ T cell. The expression of SEC11A was positively correlated to drug resistance to anticancer drugs. Conclusion: These findings suggested that SEC11A could act as a prognostic biomarker across pan-cancer. Upregulation of SEC11A was in relation to tumor immunosuppressive status. Collectively, our results offered a valuable resource that might guide mechanistic and therapeutic analysis of SEC11A across cancers.

Tumor-derived exosomes (exo) could modulate the biological behaviors of human umbilical vein endothelial cells (HUVECs). Here, the role of microRNA (miR)-10a-5p-modified gastric cancer (GC) cells-derived exo for HUVECs was studied. GC tissue specimens were collected, and miR-10a-5p and zinc finger MYND-type containing 11 (ZMYND11) levels were determined. HUVECs interfered with ZMYND11 or miR-10a-5p-related oligonucleotides. Exo was extracted from GC cells (HGC-27 exo), and miR-10a-5p mimic-modified HGC-27 exo were co-cultured with HUVECs. HUVECs viability, migration and angiogenesis were evaluated, and miR-10a-5p/ZMYND11 crosstalk was explored. It was observed that GC patients had raised miR-10a-5p and reduced ZMYND11, and miR-10a-5p negatively mediated ZMYND11 expression. Suppression of miR-10a-5p or overexpression of ZMYND11 inhibited viability, migration and tube formation ability of HUVECs. Notably, miR-10a-5p mimic-modified HGC-27 exo enhanced the viability, migration and tube formation ability of HUVECs, but this effect was impaired after up-regulating ZMYND11. In summary, miR-10a-5p from GC cells-derived exo enhances viability and migration of HUVECs by suppressing ZMYND11., Graphical abstract

Background: Increasing evidence demonstrated that autophagy paly a crucial role in initiation and progression of OSCC. The aim of this study was to explore the prognostic value of autophagy-related genes(ATGs) in patients with OSCC. RNA-seq and clinical data were downloaded from TCGA database following extrating ATGs expression profiles. Then, differentially expressed analysis was performed in R software EdgeR package, and the potential biological function of differentially expressed ATGs were explored by GO and KEGG enrichment analysis. Furthermore, a risk score model based on ATGs was constructed to predict the overall survival. Moreover, univariate, multivariate cox regression and survival analysis were used to select autophagy related biomarkers which were identified by RT-qPCR in OSCC cell lines, OSCC tissues and matched normal mucosal tissues. Results: Total of 232 ATGs were extrated and 37 genes were differentially expressed in OSCC. GO and KEGG analysis indicated that these differentially expressed genes were mainly located in autophagosome membrane, and associated with apoptosis, platinum drug resistance, ErbB signaling pathway and TNF signaling pathway. Furthermore, a risk score model including 9 variables was constructed and subsequently identified with univariate, multivariate cox regression, survival analysis and Receiver Operating Characteristic curve(ROC). Moreover, ATG12 and BID were identified as potential autophagy related biomakers. Conclusion: This study successfully constructed a risk model to predict the prognosis of patients with OSCC, and the risk score may be as a independent prognostic biomarker in OSCC. ATG12 and BID were identified as potential biomarkers in tumor diagnosis and treatment of OSCC.

This paper reports a rare autopsy case, a 21-years old healthy female worker, who died of acute iatrogenic water intoxication after she had swallowed powder scraped off 17 matches in an apparent suicide attempt. Gastric lavage was performed as she was wrongly considered to have taken poison containing phosphorus. She was given 7.8 1 water within 2 h. The pathological findings and 16 cases from the literature between 1978-1994 are reviewed.

We report a case of homicide due to intravenous mercury injection followed by meperidine and sodium cyanide injection. A 35-year-old woman was found dead in bed at home by her husband. Reportedly, she had been sick for more than 5 months. Initial death investigation revealed no evidence of foul play. Her death was believed to be natural. Therefore, her body was buried without an autopsy. Two months after death, her family requested an autopsy because they suspected her physician husband killed her. Her body was exhumed, and an autopsy was performed. Postmortem examination revealed numerous metallic mercury globules in the pulmonary arteries. Toxicological analysis revealed a high concentration of mercury in the tissue samples of the lungs, liver, heart, and kidney. In addition, cyanide and meperidine were also found in the heart and liver. The detailed case history and postmortem examination findings are described.

This paper reports the results of a forensic pathological study of 89 autopsy cases of Sudden Coronary Death (SCD). Of 89 cases, 63 (52 male, 11 female) were narrowed by 76–100% in cross-selectional area (XSA) of the coronary artery (CA) and 26 (22 male, 4 female), by 51–75%. Atherosclerotic plaques in the CA were serious and extensive, especially in the left anterior descending and often involved several branches of CA at the same time. Recent thrombosis was found in 18 cases, haemorrhage in plaques in 17 cases. Only 2 cases had visible acute myocardial infarction. Inflammatory cell infiltration was found in coronary plaques in 36 cases. Myocardial fibrosis or small scar formation was detected in 51 cases. It is suggested that although the incidence of coronary heart disease (CHD) is low in China, SCD is the commonest mode of Sudden Unexpected Death. The majority of SCD (52%) were middle aged males (30–49 years old). Most of the cases died suddenly during sleep without any clear precipitating factors. The characteristics of occurrence and pathological changes in the CA and myocardium and the pathological diagnosis of SCD are also analysed and discussed.

In China, the ethylacetate extract of the herb Tripterygium wilfordii Hook f (TWEE), containing the major active ingredient triptolide, is often used with favorable effect on rheumatoid arthritis patients, in alternation with the use of prednisone. The mechanism of this therapeutic effect, however, has not been completely delineated. In this study, we studied how TWEE and prednisone affect the pituitary and adrenal glands in rats. Thirty normal male Sprague-Dawley rats (ten per group) were randomly assigned to receive: (1) TWEE (25 mg/kg, twice a day), (2) prednisone (2 mg/kg, twice a day), or (3) vehicle (control) (0.5% sodium carboxymethyl cellulose 1 ml, twice a day), orally for 30 days. Pituitary and trunk blood were collected on day 31. Adrenocorticotropic hormone (ACTH) expression in the pituitary gland was assessed morphologically by immunohistochemical techniques. Plasma ACTH concentrations and serum corticosterone concentrations were quantitatively measured by radioimmunoassay. We found that TWEE significantly increased plasma ACTH concentration and serum corticosterone concentration and dramatically increased the number of ACTH-positive cells in the pituitary. Our findings indicate that TWEE can promote the synthesis and secretion of ACTH cells — in the pars distalis of the rat pituitary gland and the production of corticosterone in the zone fasciculata of the adrenal cortex. Our results indicate that TWEE has a cortical hormone-like function and can promote adrenal cortex function by activating the hypothalamus-pituitary-adrenal axis.