MRI-Based Clinical-Imaging-Radiomics Nomogram Model for Discriminating Between Benign and Malignant Solid Pulmonary Nodules or Masses.

RATIONALE AND OBJECTIVES: Pulmonary nodules or masses are highly prevalent worldwide, and differential diagnosis of benign and malignant lesions remains difficult. Magnetic resonance imaging (MRI) can provide functional and metabolic information of pulmonary lesions. This study aimed to establish a nomogram model based on clinical features, imaging features, and multi-sequence MRI radiomics to identify benign and malignant solid pulmonary nodules or masses. MATERIALS AND METHODS: A total of 145 eligible patients (76 male; mean age, 58.4 years ± 13.7 [SD]) with solid pulmonary nodules or masses were retrospectively analyzed. The patients were randomized into two groups (training cohort, n = 102; validation cohort, n = 43). The nomogram was used for predicting malignant pulmonary lesions. The diagnostic performance of different models was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of these patients, 95 patients were diagnosed with benign lesions and 50 with malignant lesions. Multivariate analysis showed that age, DWI value, LSR value, and ADC value were independent predictors of malignant lesions. Among the radiomics models, the multi-sequence MRI-based model (T1WI+T2WI+ADC) achieved the best diagnosis performance with AUCs of 0.858 (95%CI: 0.775, 0.919) and 0.774 (95%CI: 0.621, 0.887) for the training and validation cohorts, respectively. Combining multi-sequence radiomics, clinical and imaging features, the predictive efficacy of the clinical-imaging-radiomics model was significantly better than the clinical model, imaging model and radiomics model (all P < 0.05). CONCLUSION: The MRI-based clinical-imaging-radiomics model is helpful to differentiate benign and malignant solid pulmonary nodules or masses, and may be useful for precision medicine of pulmonary diseases.

IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation.

Cervical cancer continues to be a concern, and the prognosis of locally advanced cervical cancer remains poor. IMPA2 was previously identified as a potential oncogene and regulator of tumor apoptosis. In this study, we aim to further elucidate the underlying mechanisms of IMPA2 gene in the regulation of cervical cancer apoptosis. First, we identify AIFM2 as an upregulated gene in IMPA2-silenced cervical cancer cells, and inhibition of AIFM2 reverses IMPA2 knockdown-induced apoptosis. Further study reveals that AIFM2 regulates cell apoptosis in a mitochondrial-dependent manner with a redistribution of mitochondrial membrane potential and intracellular Ca 2+ levels. However, the analysis of the STRING database and our experimental results show that AIFM2 has little effect on cervical cancer progression and survival. Further mechanistic study demonstrates that IMPA2 and AIFM2 silencing inhibits apoptosis by activating p53. Meanwhile, the knockdown of IMPA2 enhances the chemosensitivity of cervical cancer cells by strengthening paclitaxel-induced apoptosis. Based on the above results, the IMPA2/AIFM2/p53 pathway may be a new molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. Our findings display a novel function of IMPA2 in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance of AIFM2 and p53 expression, potentially making it a novel therapeutic target for cervical cancer treatment.

Design, synthesis, and evaluation of 4(1H)-quinolinone and urea derivatives as KRASG12C inhibitors with potent antitumor activity against KRAS-mutant non-small cell lung cancer.

KRASG12C is the most prevalent KRAS mutation in non-small cell lung cancer (NSCLC) and has emerged as a promising therapeutic target. Herein, two series of novel 4(1H)-quinolinone and urea compounds were designed based on the reported KRASG12C inhibitor SH-9. Many compounds showed significantly growth inhibitory activity against human NSCLC cells with KRASG12C mutation in cell viability assays. Compound 20a exhibited an IC50 value of 0.5 µM in KRASG12C-mutant NCI-H358 cells with 21-fold selectivity over KRASWT NCI-H2228 cells. LC-MS analysis indicated that compounds 14c, 14h and 20a covalently bound to KRASG12C rather than KRASWT. Moreover, these compounds could remarkably trap KRASG12C in its inactive state by blocking SOS1-mediated GDP/GTP exchange. Furthermore, treatment of NCI-H358 but not NCI-H2228 cells with 20a dose-dependently reduced the phosphorylation of KRAS downstream effectors ERK and AKT. Importantly, 20a significantly inhibited tumor growth in NCI-H358 xenograft models by suppressing KRASG12C signalling. These results indicate that 20a is a promising candidate worthy of further investigation.

Bipolar versus monopolar transurethral resection of non-muscle-invasive bladder cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety of bipolar and monopolar transurethral resection of bladder tumors (TURBT) in non-muscle invasive bladder cancer (NMIBC) treatment. METHODS: A systematic search of all Randomized Controlled Trials (RCTs), which compared bipolar TURBT (bTURBT) and monopolar TURBT (mTURBT) in NMIBC treatment, were performed in PubMed, Web of Science, Cochrane Library and Embase up to February 1, 2019. We evaluated their efficacy by operative time, hospitalization time, catheterization time, and recurrence rate. While obturator jerk, bladder perforation, thermal damage, and overall complications were used to evaluate their safety. RESULTS: A total of 13 RCTs, involving 2379 patients, were included. There were no statistically significant differences in efficacy between bTURBT and mTURBT in NMIBC treatment, such as operative time (p = 0.12), hospitalization time (p = 0.13), catheterization time (p = 0.50), and recurrence rate (p = 0.88). Compared to the safety in mTURBT in NMIBC treatment, no significant advantages were observed in that in bTURBT as well, such as obturator jerk (p = 0.12), bladder perforation (p = 0.11), thermal damage (p = 0.24), and overall complications (p = 0.65). CONCLUSIONS: Our analysis demonstrated that bTURBT has no significant advantages in efficacy and safety in NMIBC treatment compared to that in mTURBT. Thus, bTURBT could not completely replace mTURBT as a safer and more effective NMIBC treatment.

High ratio of C-reactive protein/procalcitonin predicts Mycoplasma pneumoniae infection among adults hospitalized with community acquired pneumonia.

There is limited data on serum biomarkers in distinguishing Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral pneumoniae (VP) etiologies of community-acquired pneumonia (CAP). A retrospective study of inpatients diagnosed with CAP at the First Affiliated Hospital of Dali University (Dali, Yunnan, China) between January 2018 and June 2020 was conducted. The demographic, clinical and laboratory data of the patients with CAP were analyzed. Univariate analyses identified predictors for MP infections. The discriminative power of C-reactive protein (CRP), procalcitonin (PCT), CRP/PCT and CRP/PCT >350 µg/ng was assessed by area under the curve (AUC) of the receiver operating characteristic (ROC) curves. A total of 552 CAP patients, including 247 (44.7%) with MP, 152 (27.6%) with SP and 153 (27.7%) with influenza A and B viruses, were enrolled. When comparing MP with SP, cough and CRP/PCT >350 µg/ng (odds ratio [OR]) 2.88, p < .001) were predictors for MP. CRP/PCT >350 µg/ng had 76% sensitivity and 100% specificity (AUC = 0.89, p < .001, 95% confidence interval [CI]:0.81-0.94) to predict MP infections. Furthermore, similar results were again obtained when comparing MP with VP. CRP/PCT >350 µg/ng present better information (OR: 4.70; AUC = 0.92, p < .001, 87% sensitivity and 100% specificity). In addition, comparing MP and non-MP (SP and VP combined), CRP/PCT >350 µg/ng exhibited excellent performance (AUC = 0.90, 95%CI 0.83-0.95, p < .001, 76% sensitivity and 100% specificity). CRP/PCT ratio may be a potential index to distinguish MP-CAP from non-MP-CAP.

Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Pediatric Sepsis.

BACKGROUND Sepsis is an extremely common health issue with a considerable mortality rate in children. Our understanding about the pathogenic mechanisms of sepsis is limited. The aim of this study was to identify the differential expression genes (DEGs) in pediatric sepsis through comprehensive analysis, and to provide specific insights for the clinical sepsis therapies in children. MATERIAL AND METHODS Three pediatric gene expression profiles (GSE25504, GSE26378, GSE26440) were downloaded from the Gene Expression Omnibus (GEO) database. The difference expression genes (DEGs) between pediatric sepsis and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. RESULTS Totally, 160 overlapping upward genes and 61 downward genes were identified. In addition, 5 KEGG pathways, including hematopoietic cell lineage, Staphylococcus aureus infection, starch and sucrose metabolism, osteoclast differentiation, and tumor necrosis factor (TNF) signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 9 hub genes including ITGAM, TLR8, IL1ß, MMP9, MPO, FPR2, ELANE, SPI1, and C3AR1 were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including has-miR-204-5p, has-miR-211-5p, has-miR-590-5p, and has-miR-21-5p, were predicted as possibly the key miRNAs. CONCLUSIONS Our findings will contribute to identification of potential biomarkers and novel strategies for pediatric sepsis treatment.

Expression of FXR and HRG and their clinicopathological significance in benign and malignant pancreatic lesions.

AIMS: The following study examines the FXR and HRG expression in benign and malignant lesions of the pancreas and evaluates the association between FXR and HRG expression with clinicopathological features and prognosis of pancreatic cancer. MATERIALS AND METHODS: Immunohistochemistry of FXR and HRG was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma (PDAC) specimens, 35 paracancer samples (2 cm away from the tumor, when possible or available), 55 benign lesions and 13 normal tissue samples. RESULTS: The percentage of cases with positive FXR and negative HRG expression was significantly higher in PDAC compared to pericancerous tissues, benign lesions and normal tissues (P<0.05 or P<0.01). In pancreatic tissues with benign lesions, tissues with positive FXR and/or negative HRG protein expression exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive FXR and negative HRG expressions was significantly higher in PDAC with lymph node metastasis, invasion, and TNM stage III+IV disease (P<0.05 or P<0.01). The expression of FXR was negatively correlated with HRG (P<0.05). In addition, the univariate Kaplan-Meier analysis showed that positive FXR and negative HRG expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, and invasion were closely associated with decreased overall survival in PDAC patients (P<0.05 or P<0.01). Moreover, multivariate Cox regression analysis identified that positive FXR and negative HRG expression were independent factors for poor prognosis in PDAC. The AUC for FXR was (AUC=0.709, 95% CI: 0.632-0.787), and for HRG was (AUC=0.719, 95% CI: 0.643-0.796) in PDAC compared to benign lesions. CONCLUSIONS: Positive FXR and negative HRG expression are closely associated with the carcinogenesis, clinical, pathological and biological behaviors, and poor prognosis in PDAC.

In silico analyses for potential key genes associated with gastric cancer.

BACKGROUND: Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer. In this study, we aim to identify the hub genes and investigate the underlying molecular mechanisms of GC. METHODS: To explore potential therapeutic targets for GC,three expression profiles (GSE54129, GSE33651, GSE81948) of the genes were extracted from the Gene Expression Omnibus (GEO) database. The GEO2R online tool was applied to screen out differentially expressed genes (DEGs) between GC and normal gastric samples. Database for Annotation, Visualization and Integrated Discovery was applied to perform Gene Ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network of these DEGs was constructed using a STRING online software. The hub genes were identified by the CytoHubba plugin of Cytoscape software. Then, the prognostic value of these identified genes was verified by gastric cancer database derived from Kaplan-Meier plotter platform. RESULTS: A total of 85 overlapped upregulated genes and 44 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, endodermal cell differentiation, and endoderm formation. Moreover, five KEGG pathways were significantly enriched, including ECM-receptor interaction, amoebiasis, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, protein digestion and absorption. By combining the results of PPI network and CytoHubba, a total of nine hub genes including COL1A1, THBS1, MMP2, CXCL8, FN1, TIMP1, SPARC, COL4A1, and ITGA5 were selected. The Kaplan-Meier plotter database confirmed that overexpression levels of these genes were associated with reduced overall survival, except for THBS1 and CXCL8. CONCLUSIONS: Our study suggests that COL1A1, MMP2, FN1, TIMP1, SPARC, COL4A1, and ITGA5 may be potential biomarkers and therapeutic targets for GC. Further study is needed to assess the effect of THBS1 and CXCL8 on GC.

Gas-phase intramolecular hydroxyl-amino exchange of protonated arginine and verified by the synthetic intermediate compound.

A new fragmentation process was proposed to interpret the characteristic product ion at m/z 130 of protonated arginine. The α-amino group was dissociated from protonated arginine and then combined with the (M + H-NH3 ) fragment to form an ion-neutral complex which further generated a hydroxyl-amino exchange intermediate compound through an ion-molecule reaction. This intermediate compound was synthesized from argininamide through a diazo reaction, and then the reaction mixture was analyzed using liquid chromatography combined with mass spectrometry (LC-MS). The collision-induced dissociation experiments under the same conditions revealed that this intermediate compound produced the characteristic product ion at m/z 130 as well as protonated arginine, and in addition, density functional theory calculations were performed to confirm simultaneous loss of NH3 and CO from this intermediate to give the m/z 130 ion.