Identification and validation of prognostically relevant gene signature in melanoma

Background. Currently, effective genetic markers are limited to predict the clinical outcome of melanoma. High-throughput multiomics sequencing data have provided a valuable approach for the identification of genes associated with cancer prognosis. Method. The multidimensional data of melanoma patients, including clinical, genomic, and transcriptomic data, were obtained from The Cancer Genome Atlas (TCGA). These samples were then randomly divided into two groups, one for training dataset and the other for validation dataset. In order to select reliable biomarkers, we screened prognosis-related genes, copy number variation genes, and SNP variation genes and integrated these genes to further select features using random forests in the training dataset. We screened for robust biomarkers and established a gene-related prognostic model. Finally, we verified the selected biomarkers in the test sets (GSE19234 and GSE65904) and on clinical samples extracted from melanoma patients using qRT-PCR and immunohistochemistry analysis. Results. We obtained 1569 prognostic-related genes and 1101 copy-amplification, 1093 copy-deletions, and 92 significant mutations in genomic variants. These genomic variant genes were closely related to the development of tumors and genes that integrate genomic variation. A total of 141 candidate genes were obtained from prognosis-related genes. Six characteristic genes (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) were selected by random forest feature selection, many of which have been reported to be associated with tumor progression. Cox regression analysis was used to establish a 6-gene signature. Experimental verification with qRT-PCR and immunohistochemical staining proved that these selected genes were indeed expressed at a significantly higher level compared with the normal tissues. This signature comprised an independent prognostic factor for melanoma patients. Conclusions. We constructed a 6-gene signature (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) as a novel prognostic marker for predicting the survival of melanoma patients

A 5-year review of invasive fungal infection at an academic medical center

Background: Invasive fungal infection (IFI) is one of the most common nosocomial infections. However, data on the epidemiology of IFI and susceptibility to antifungal agents in China are quite limited, and in particular, no current data exist on the microbiological, and clinical characteristics of IFI patients in Northeast China. Objectives: The purpose of this study was to provide a retrospective review of the clinical characteristics, laboratory test results, and risk factor predictions of inpatients diagnosed with IFI. Multivariate regression analysis was used to assess prognostic factors associated with the mortality of these patients. Methods: We retrospectively analyzed the results from 509 patients with IFI extracted from the First Hospital of China Medical University from January 2013 to January 2018. Results: Neutrophil numbers, total bilirubin, length of stay in the ICU, renal failure, use of immunosuppressants within the past 30 days, stomach tube placement and septic shock were risk factors for death from IFI. Recent surgery (within 2 weeks) and drainage tube placement did not increase mortality in these IFI patients. Increased serum levels of PCT (AUC 0.601, 95% CI 0.536–0.665, P = 0.003) and CRP (AUC 0.578, 95% CI 0.512–0.644, P = 0.020) provided effective predictors of 30-day mortality rates. Conclusions: We report for the first time epidemiological data on invasive fungal infections in Northeast China over the past 5 years. Despite the limited available clinical data, these findings will greatly aid clinical health care workers with regard to the identification, prevention, and treatment of IFI in hospitalized patients

LncRNA BASP1-AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma

Melanoma is a fatal skin malignant tumor with a poor prognosis. We found that long noncoding RNA BASP1-AS1 is essential for the development and prognosis of melanoma. The methylation, RNA sequencing, copy number variation, mutation data, and sample follow-up information of melanoma from The Cancer Genome Atlas (TCGA) were analyzed using weighted gene co-expression network analysis and 366 samples common to the three omics were selected for multigroup clustering analysis. A four-gene prognostic model (BASP1-AS1, LOC100506098, ARHGAP27P1, and LINC01532) was constructed in the TCGA cohort and validated using the GSE65904 series. The expression of BASP1-AS1 was upregulated in melanoma tissues and various melanoma cell lines. Functionally, the ectopic expression of BASP1-AS1 promoted cell proliferation, migration, and invasion in both A375 and SK-MEL-2 cells. Mechanically, BASP1-AS1 interacted with YBX1 and recruited it to the promoter of NOTCH3, initiating its transcription process. The activation of the Notch signaling then resulted in the transcription of multiple oncogenes, including c-MYC, PCNA, and CDK4, which contributed to melanoma progression. Thus, BASP1-AS1 could act as a potential biomarker for cutaneous malignant melanoma

Machine-learning based prediction and analysis of prognostic risk factors in patients with candidemia and bacteraemia: a 5-year analysis

Bacteraemia has attracted great attention owing to its serious outcomes, including deterioration of the primary disease, infection, severe sepsis, overwhelming septic shock or even death. Candidemia, secondary to bacteraemia, is frequently seen in hospitalised patients, especially in those with weak immune systems, and may lead to lethal outcomes and a poor prognosis. Moreover, higher morbidity and mortality associated with candidemia. Owing to the complexity of patient conditions, the occurrence of candidemia is increasing. Candidemia-related studies are relatively challenging. Because candidemia is associated with increasing mortality related to invasive infection of organs, its pathogenesis warrants further investigation. We collected the relevant clinical data of 367 patients with concomitant candidemia and bacteraemia in the first hospital of China Medical University from January 2013 to January 2018. We analysed the available information and attempted to obtain the undisclosed information. Subsequently, we used machine learning to screen for regulators such as prognostic factors related to death. Of the 367 patients, 231 (62.9%) were men, and the median age of all patients was 61 years old (range, 52–71 years), with 133 (36.2%) patients aged >65 years. In addition, 249 patients had hypoproteinaemia, and 169 patients were admitted to the intensive care unit (ICU) during hospitalisation. The most common fungi and bacteria associated with tumour development and Candida infection were Candida parapsilosis and Acinetobacter baumannii, respectively. We used machine learning to screen for death-related prognostic factors in patients with candidemia and bacteraemia mainly based on integrated information. The results showed that serum creatinine level, endotoxic shock, length of stay in ICU, age, leukocyte count, total parenteral nutrition, total bilirubin level, length of stay in the hospital, PCT level and lymphocyte count were identified as the main prognostic factors. These findings will greatly help clinicians treat patients with candidemia and bacteraemia

Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes

Background and Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein–protein interaction (PPI) was performed. Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts

Machine‑learning based prediction of prognostic risk factors in patients with invasive candidiasis infection and bacterial bloodstream infection: a singled centered retrospective study

Background Invasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited. Methods We included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3). Results Of the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25–74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level. Conclusion Our results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level

Analysis on the Experimental Teaching Reform of Landscape Design under the New Situation

The experimental course of Landscape Design is based on the training of design ability, which breaks the traditional mode of students' self-completion of homework, and finally changes from the traditional mode of teachers' comments to the task of real site design to carry out course experiments, making students construct relevant theoretical knowledge in the process of completing specific projects. After professional designers' in-depth and detailed, systematic analysis and comments, the training of students' professional ability is highlighted. In the process of the experiment, it focuses on link with the industry and enterprises, and obtains the professional abilities and professional skills needed by the enterprises according to the method of situational learning theory

Experimental Investigation on the Durability of Glass Fiber-Reinforced Polymer Composites Containing Nanocomposite

Nanoclay layers incorporated into polymer/clay nanocomposites can inhibit the harmful penetration of water and chemicals into the material, and thus the durability of glass fiber-reinforced polymer (GFRP) composites should be enhanced by using polymer/clay nanocomposite as the matrix material. In this study, 1.5 wt% vinyl ester (VE)/organoclay and 2 wt% epoxy (EP)/organoclay nanocomposites were prepared by an in situ polymerization method. The dispersion states of clay in the nanocomposites were studied by performing XRD analysis. GFRP composites were then fabricated with the prepared 1.5 wt% VE/clay and 2.0 wt% EP/clay nanocomposites to investigate the effects of a nanocomposite matrix on the durability of GFRP composites. The durability of the two kinds of GFRP composites was characterized by monitoring tensile properties following degradation of GFRP specimens aged in water and alkaline solution at 60°C, and SEM was employed to study fracture behaviors of aged GFRP composites under tension. The results show that tensile properties of the two types of GFRP composites with and without clay degrade significantly with aging time. However, the GFRP composites with nanoclay show a lower degradation rate compared with those without nanoclay, supporting the aforementioned hypothesis. And the modification of EP/GFRP enhanced the durability more effectively

Exposure to organochlorine pesticides is an independent risk factor of hepatocellular carcinoma: A case-control study

Primary hepatocellular carcinoma (HCC) is highly prevalent in China. Although hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are considered the major risk factors, among the high-risk cohorts only a small fraction develops liver cancer. Therefore, we investigated whether organochlorine pesticide exposure contributed to HCC risk in the Xiamen population. The questionnaire database was built from 346 HCC cases and 961 healthy controls during 2007-2009. The serum levels of alpha-, beta-, gamma-, delta-HCH, 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (p,p'-DDT), (1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis (o-chlorophenyl) ethane and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane were measured by gas chromatography-tandem mass spectrometer, and statistical analysis was done using SPSS16. Significantly, we observed p,p'-DDT and p,p'-DDE, and at the first time beta-HCH displayed quartile dose-dependent HCC risk trends; p,p'-DDT showed positive (i.e., synergistic) interactions with HBV, diabetes mellitus. AFB1 and polyaromatic hydrocarbon (PAH) exposure, but negative (i.e., antagonistic) interaction with heavy drinking; p,p'-DDE had positive interaction with PAH but negative interaction with HBV and p.p'-DDT; and beta-HCH positively interacted with p,p'-DDT but negatively interacted with heavy drinking and diabetes. p,p'-DDT, p,p'-DDE and beta-HCH were independent HCC risk factors. Because of their synergistic interactions with other factors, the high-level exposure combined with common AFB1 and HBV exposure in the investigated area may greatly enhance the risk of HCC. Journal of Exposure Science and Environmental Epidemiology (2012) 22, 541-548; doi:10.1038/jes.2011.29; published online 14 September 2011Chinese Academy of Sciences (CAS) 100 Talents Program for Human Exposure; Xiamen Municipal Science and Technology Program [3502Z20073015]; CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08]; Ministry of Science and Technology of the People's Republic of China for Combined Pollution and Ecosystem Health in Urban Agglomeration [2009DFB90120