Clinical Characteristics and Molecular Insights of Carbapenem-Resistant Klebsiella pneumoniae Isolates from Patients in Intensive Care Units.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP), a significant worldwide public health threat, is common in patients in intensive care units. Methods: A retrospective study was conducted over a period of 22 months to assess the risk factors associated with infection caused by CRKP isolates. Strain identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and antimicrobial sensitivity was assessed using the micro broth dilution method and Kirby-Bauer test. The genes blaKPC, blaOXA-48, blaNDM, blaVIM, and blaGES were amplified using polymerase chain reaction (PCR), followed by sequencing of the PCR products. The polymerase hypermucoviscosity phenotype was determined using the string test. Capsular serotypes (K1, K2) and presence of the virulence gene (rmpA) in positive isolates were investigated using phenotypic tests followed by PCR. Results: Length of hospitalization and use of carbapenems were associated with CRKP infection. CRKP isolates exhibited extensive drug resistance, but retained sensitivity to colistin and ceftazidime-avibactam (CZA). The main gene detected in 35 CRKP isolates was blaKPC-2. In addition, 11 strains were positive in the string test, and two of these strains carried rmpA. Conclusions: Prolonged hospitalization and carbapenem exposure increased the risk of CRKP infection in intensive care unit (ICU) patients. The prevalence of CRKP carrying the blaKPC-2 gene was high, and suspected hypervirulent carbapenem-resistant K. pneumoniae isolates were scattered.

Lysosome-related genes: A new prognostic marker for lung adenocarcinoma.

Currently, a reliable early prognostic marker has not been identified for lung adenocarcinoma (LUAD), the most common malignancy. Recent studies demonstrated that lysosomal rupture is involved in cancer migration, progression, and immune microenvironment formation. We performed a bioinformatics analysis of lysosomal rupture to investigate whether lysosome-related genes (LRGs) are key in LUAD. The analysis identified 23 LRGs. Cytoscape visualization identified 10 core genes (CCNA2, DLGAP5, BUB1B, KIF2C, PBK, CDC20, NCAPG, ASPM, KIF4A, ANLN). With the 23 LRGs, we established a new risk scoring rule to classify patients with LUAD into high- and low-risk groups and verified the accuracy of the risk score by receiver operating characteristic curves and established a nomogram to evaluate clinical patients. Immunotherapy effectiveness between the high- and low-risk groups was evaluated based on the tumor mutational burden and analyses of immune cell infiltration and drug sensitivity. Pathway enrichment analysis revealed that lysosomes were closely associated with glucose metabolism, amino acid metabolism, and the immune response in patients with LUAD. Lysosomes are a likely new therapeutic target and provide new directions and ideas for treating and managing patients with LUAD.

Diagnostic Value of Seven Autoantibodies Combined with CEA and CA199 in Non-Small Cell Lung Cancer.

BACKGROUND: This study aimed to analyze the diagnostic value of seven autoantibodies (7-AABs) combined with carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (CA199) in non-small cell lung cancer (NSCLC) and provide a new method for early screening of NSCLC. METHODS: The serum levels of 7-AABs, CEA, and CA199 were determined in the NSCLC group (n = 615), benign lung disease group (n = 183), healthy control group (n = 236), and the other tumor group (n = 226). The receiver operating characteristic area under the curve (AUC) analyses were conducted to evaluate the diagnostic efficiency of 7-AABs combined with CEA and CA199 in NSCLC. RESULTS: The positive rate of 7-AABs detection was higher than that of a single antibody detection. The positive rate of the combination of 7-AABs in NSCLC group (27.8%) was significantly higher than that of the benign lung disease group (15.8%) and healthy control group (11.4%). The positive rate of MAGE A1 was higher in patients with squamous cell carcinoma than adenocarcinoma. The levels of CEA and CA199 in the NSCLC group were significantly higher than those of the healthy control group, but had no statistical differences compared with those of benign lung disease group. The sensitivity, specificity, and AUC of the 7-AABs were 27.8%, 86.6%, and 0.665, respectively. The combination of 7-AABs with CEA and CA199 increased the sensitivity to 34.8% and AUC to 0.689. CONCLUSIONS: The diagnostic efficiency was enhanced by a combination of 7-AABs, CEA, and CA199 in NSCLC, which was helpful in the screening of NSCLC.

A single region of the Phytophthora infestans avirulence effector Avr3b functions in both cell death induction and plant immunity suppression.

As a destructive plant pathogen, Phytophthora infestans secretes diverse host-entering RxLR effectors to facilitate infection. One critical RxLR effector, PiAvr3b, not only induces effector-triggered immunity (ETI), which is associated with the potato resistance protein StR3b, but also suppresses pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). To date, the molecular basis underlying such dual activities remains unknown. Based on phylogenetic analysis of global P. infestans isolates, we found two PiAvr3b isoforms that differ by three amino acids. Despite this sequence variation, the two isoforms retain the same properties in activating the StR3b-mediated hypersensitive response (HR) and inhibiting necrosis induced by three PAMPs (PiNpp, PiINF1, and PsXeg1) and an RxLR effector (Pi10232). Using a combined mutagenesis approach, we found that the dual activities of PiAvr3b were tightly linked and determined by 88 amino acids at the C-terminus. We further determined that either the W60 or the E134 residue of PiAvr3b was essential for triggering StR3b-associated HR and inhibiting PiNpp- and Pi10232-associated necrosis, while the S99 residue partially contributed to PTI suppression. Additionally, nuclear localization of PiAvr3b was required to stimulate HR and suppress PTI, but not to inhibit Pi10232-associated cell death. Our study revealed that PiAvr3b suppresses the plant immune response at different subcellular locations and provides an example in which a single amino acid of an RxLR effector links ETI induction and cell death suppression.

Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance.

Hypoxia-induced cisplatin resistance is a major challenge during non-small cell lung cancer (NSCLC) treatment. Based on previous studies, we further explored the effect of eukaryotic initiation factor 5A2 (eIF5A2) in hypoxia-induced cisplatin resistance. In this study, we found that autophagy and cisplatin resistance were increased under hypoxic conditions in three different NSCLC cell lines. Compared with that under normoxic conditions, dramatic upregulation of eIF5A2 and hypoxia inducible factor 1 subunit alpha (HIF-1α) levels were detected under hypoxia exposure. Small interfering RNA silencing of HIF-1α resulted in decreased expression of eIF5A2, indicating that eIF5A2 acts downstream of HIF-1α. In addition, the expression of eIF5A2 was significantly higher in NSCLC tumors compared with that in normal tissues. RNA silencing-mediated downregulation of eIF5A2 decreased hypoxia-induced autophagy, thereby reducing hypoxia-induced cisplatin resistance in NSCLC cells. The roles of eIF5A2 in cisplatin resistance were further validated in vivo. Combined treatment using eIF5A2-targeted downregulation together with cisplatin significantly inhibited tumor growth compared with cisplatin alone in the subcutaneous mouse model. In conclusions, eIF5A2 overexpression is involved in hypoxia-induced autophagy during cisplatin resistance. We suggest that a combination of eIF5A2 targeted therapy and cisplatin chemotherapy is probably an effective strategy to reverse hypoxia-induced cisplatin resistance and inhibit NSCLC development.

Efficacy of autoantibodies combined with tumor markers in the detection of lung cancer.

BACKGROUND: The purpose of this study was to explore the detection value of seven autoantibodies (TAAbs): p53, PGP9.5, SOX2, GBU4-5, MAGE A1, CAGE, and GAGE7 and three tumor markers: CYFRA21-1, NSE, and SCCA in the diagnosis of lung cancer. METHODS: ELISA was used to detect the levels of the TAAbs, and chemiluminescence immunoassay was used to test the levels of the tumor markers. The diagnostic efficacy of the TAAbs combined with the tumor markers for lung cancer was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The positive rate of the combined detection of seven TAAbs and three tumor markers in lung cancer (37.8%) was higher than that in other three groups. The positive rates of SOX2, GAGE7, MAGE A1, CAGE, CYFRA21-1, and SCCA had differences among the four groups. Compared with the benign lung disease group, only GAGE7, CYFRA21-1, and SCCA differed among the groups. The combined sensitivity of the TAAbs was 29.07% (AUC, 0.594), the combined sensitivity of all the markers was 37.76% (AUC, 0.660 [p < 0.05]), and Youden's index was 0.196. In the lung cancer group, CYFRA21-1 had a significant difference in age and sex, and SOX2, MAGE A1, CYFRA21-1, NSE, and SCCA were significantly different in pathological type and TNM. In contrast, p53 and GBU4-5 showed no significant differences in age, sex, pathological type, and TNM. CONCLUSIONS: The combined detection of seven TAAbs and three tumor markers could be useful in early diagnosis of lung cancer.

CircRNA6783 Inhibits Cell Proliferation and Promotes Apoptosis in Lung Adenocarcinoma.

Purpose: Circular RNA (circRNA) serves an important role in tumour genesis and development. But, little is known about its role in lung adenocarcinoma (LA). This study aimed to investigate circRNA6783 expression in peripheral whole blood (PWB) of LA and controls and explore its effect on proliferation and apoptosis in human lung adenocarcinoma cells (LAC). Patients and Methods: The levels of circRNA6783 in LA cell lines and peripheral whole blood (PWB) of 40 patients and 30 controls were detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). In order to explore the effect of circRNA6783 on LA behavior, we overexpressed circRNA6783 in NCI-H1975 cells. The impact on the proliferation of tumor cells was then examined by Cell Counting Kit 8 (CCK8) assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression levels of circRNA6783 were significantly higher in LA cell lines and PWB (P < 0.05). The diagnostic value of the area under the receiver operating characteristic curve (AUC) was 0.830, with a sensitivity of 60% and specificity of 96.7%. In addition, functional experiments showed that overexpression of circRNA6783 restrained cell proliferation, significantly increased spontaneous apoptosis. Conclusion: CircRNA6783 was upregulated in LA PWB. In vitro assessment demonstrated that circRNA6783 could act as a potential biomarker for LA diagnosis.

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma.

Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature on the basis of long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of patients with LUAD. We selected ARlncRNAs associated with prognosis to construct a model and divided each sample into different groups on the basis of risk score. The ARlncRNA signature could be recognized as an independent prognostic factor for patients with LUAD, and patients in the low-risk group had a greater survival advantage. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden. Low-risk patients had a higher PD-1, CTLA-4, and HAVCR2 expression and had a better efficacy of immune checkpoint inhibitors, including PD-1/CTLA-4 inhibitor. A reliable signature on the basis of ARlncRNAs was constructed to explore the TIME and prognosis of patients with LUAD, which could provide valuable information for individualized LUAD treatment.

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD.

The tumor immune microenvironment of lung cancer is associated with prognosis and immunotherapy efficacy. Long noncoding RNAs are identified as prognostic biomarkers associated with immune functions. We constructed a signature comprising differentially expressed immune-related lncRNAs to predict the prognosis of patients with lung adenocarcinoma. We established the immune-related lncRNA signature by pairing immune-related lncRNAs regardless of expression level and lung adenocarcinoma patients were divided into high- and low-risk groups. The prognosis of patients in the two groups was significantly different; The immune-related lncRNA signature could serve as an independent lung adenocarcinoma prognostic indicator. The signature correlated negatively with B cell, CD4+ T cell, M2 macrophage, neutrophil, and monocyte immune infiltration. Patients with low risk scores had a higher abundance of immune cells and stromal cells around the tumor. Gene set enrichment analysis showed that samples from low-risk group were more active in the IgA production in intestinal immune network and the T and B cell receptor signaling pathway. High-risk groups had significant involvement of the cell cycle, DNA replication, adherens junction, actin cytoskeleton regulation, pathways in cancer, and TGF-ß signaling pathways. High risk scores correlated significantly negatively with high CTLA-4 and HAVCR2 expression and higher median inhibitory concentration of common anti-tumor chemotherapeutics (e.g., cisplatin, paclitaxel, gemcitabine) and targeted therapy (e.g., erlotinib and gefitinib). We identified a reliable immune-related lncRNA lung adenocarcinoma prognosis model, and the immune-related lncRNA signature showed promising clinical prediction value.

Association of ERCC1 and ERCC2 Gene Polymorphisms with Pancreatic Cancer Risk: A Meta-Analysis.

In this meta-analysis, all relative literature was retrieved through the Embase and PubMed databases. Moreover, the Stata 12.0 software package was applied to calculate the pooled odds ratio (OR) of the 95% confidence interval (CI). A total of seven studies was identified to analyze the relation between ERCC1 and ERCC2 gene polymorphisms and pancreatic cancer risk. The results showed that ERCC2 rs13181 polymorphism was associated with pancreatic cancer (CC vs. AA: OR = 1.53, 95% CI = 1.24-1.90; AC vs. AA: OR = 1.06, 95% CI = 0.92-1.22; dominant model: OR = 1.16, 95% CI = 1.02-1.32; recessive model: OR = 1.39, 95% CI = 0.13-1.70). For ERCC1 rs3212986 polymorphism, a significant correlation with pancreatic cancer risk was found (TT vs. GG: OR = 2.33, 95% CI = 1.73-3.14; GT vs. GG: OR = 1.34, 95% CI = 1.11-1.63; dominant model: OR = 1.50, 95% CI = 1.25-1.80; recessive model: OR = 1.98, 95% CI = 1.50-2.62). A lack of association was found for ERCC1 rs11615 polymorphism (TT vs. CC: OR = 1.21, 95% CI = 0.93-1.56; CT vs. CC: OR = 1.02, 95% CI = 0.87-1.21; dominant model: OR = 1.43, 95% CI = 0.80-2.50; recessive model: OR = 0.99, 95% CI = 0.65-1.51).

Clinical value of seven autoantibodies combined detection in the diagnosis of lung cancer.

BACKGROUND: To analyze the clinical value of seven autoantibodies (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE) in lung cancer patients. METHODS: ELISA was used to determine serum levels of seven autoantibodies in 177 patients with lung cancer, 201 healthy persons, and 210 patients with benign pulmonary diseases. Positive rates of 7 autoantibodies were analyzed; receiver operating characteristic (ROC) curves were drawn to analyze their diagnostic efficiency in lung cancer and to compare the positive rate of seven kinds of autoantibody combined detection of lung cancer patients with different clinicopathological features. RESULTS: The positive rate of seven autoantibodies in all subjects was 13.44%. The positive rate of seven autoantibodies in lung cancer was 25.42%. The positive rate of the combined detection of seven autoantibodies in the lung cancer group was significantly higher than that in healthy control group (χ2  = 19.76, P < .001) and benign lung disease group (χ2  = 21.44, P < .001). Sensitivity, specificity, and AUCROC of the seven autoantibodies were 25.42%, 91.75%, and 0.683, respectively. Sensitivity and AUCROC were higher than those of the single autoantibody detection. Positive rates of seven autoantibodies in different pathological types and clinical stages of lung cancer patients were significantly different (P < .05). CONCLUSIONS: The combined detection of 7 autoantibodies in lung cancer has some clinical value for the auxiliary diagnosis of lung cancer.

Circular RNA expression profile in peripheral whole blood of lung adenocarcinoma by high: Throughput sequencing.

BACKGROUND: Lung adenocarcinoma (LA) is a most common form of non-small cell lung cancer (NSCLC). To date, there are still no effective early diagnosis methods for patients to be cured in time. Noncoding RNA plays an important role in oncogenesis and tumor development. The expression profile of circular RNA (circRNA) in peripheral whole blood (PWB) of LA has not been systematically investigated. In this study, we identified the differentially expressed (DE) circRNAs in PWB of LA by high-throughput sequencing. METHODS: Five paired LA and normal participants PWB samples were chosen to investigate the expression profile of circRNAs by high-throughput sequencing. Twenty LA and 10 normal controls PWB samples were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis was also performed to predict the function of circRNAs in PWB. RESULTS: A total of 10566 circRNAs were identified and annotated, most of the circRNAs were exonic (78.14%). Statistical analysis revealed 4390 DE circRNAs, in which were 3009 upregulated circRNAs and1381downregulated circRNAs in LA. RT-PCR results showed that circRNA expression in LA was higher than that in controls. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain degree. The current study is the first to systematically characterize and annotate circRNA expression in PWB of LA. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor related miRNAs, indicating that circRNAs might involve in development and progression of LA. CONCLUSIONS: Our study revealed that circRNAs were abnormally expressed in PWB of LA, which might offer potential targets for the early diagnosis of the disease and new genetic insights into LA.

[Research Progress of Circular RNA in Lung Cancer].

Lung cancer is one of the most important malignant tumors of human health and life in the world, and is the leading cause of death in the world. At present, it is believed that it is caused by many factors. Circular RNA (circRNA), as a class of non-coding RNA family, has covalently closed loop structure. CircRNA is abundant in different cells. CircRNAs due to the special structure, with a high degree of specificity, conservation and stability, may have a potential clinical value in the development of lung cancer. The biological function of circRNA is multi-faceted, including miRNA sponge, transcriptional and alternative splicing, protein coding , and so on. Currently, the role and mechanism of circRNA in lung cancer is not very clear. In this paper, the characteristics, function, mechanism and the role of circRNAs in the occurrence and development of lung cancer are reviewed.
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[Value of combined detection of GP73 and alpha-fetoprotein in diagonosis of hepatocellular carcinoma].

OBJECTIVE: To explore the diagnostic value of the measurement of serum Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC). METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum GP73 in the 81 cases of HCC, 71 cases of chronic hepatitis or cirrhosis (CH/LC) and 65 cases of healthy blood donors, and to evaluate the sensitivity and specificity in the diagnosis of HCC through the ROC curves. RESULTS: The average levels of serum GP73 in HCC, CH/LC and Normal groups were (152.67 +/- 33.59) ng/ml, (93.15 +/- 20.02) ng/ml and (58.95 +/- 17.29) ng/ml(o) After calculating through the ROC curves, 120 ng/ml was set as the optimal cut-off point, GP73 has a sensitivity of 77.80% and a specificity of 78.00%. CONCLUSIONS: GP73 as a serum marker in the diagnosis of HCC had a higher sensitivity than AFP, and the combined detection of GP73 and AFP could improve HCC diagnosis.