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Backgrounds: The in-hospital mortality in lung cancer patients admitted to intensive care unit (ICU) is extremely high. This study intended to adopt machine learning algorithm models to predict in-hospital mortality of critically ill lung cancer for providing relative information in clinical decision-making. Methods: Data were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) for a training cohort and data extracted from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) database for a validation cohort. Logistic regression, random forest, decision tree, light gradient boosting machine (LightGBM), eXtreme gradient boosting (XGBoost), and an ensemble (random forest+LightGBM+XGBoost) model were used for prediction of in-hospital mortality and important feature extraction. The AUC (area under receiver operating curve), accuracy, F1 score and recall were used to evaluate the predictive performance of each model. Shapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance of each feature. Results: Overall, there were 653 (24.8%) in-hospital mortality in the training cohort, and 523 (21.7%) in-hospital mortality in the validation cohort. Among the six machine learning models, the ensemble model achieved the best performance. The top 5 most influential features were the sequential organ failure assessment (SOFA) score, albumin, the oxford acute severity of illness score (OASIS) score, anion gap and bilirubin in random forest and XGBoost model. The SHAP summary plot was used to illustrate the positive or negative effects of the top 15 features attributed to the XGBoost model. Conclusion: The ensemble model performed best and might be applied to forecast in-hospital mortality of critically ill lung cancer patients, and the SOFA score was the most important feature in all models. These results might offer valuable and significant reference for ICU clinicians' decision-making in advance. [ABSTRACT FROM AUTHOR]

Clinical prostate cancer (PCa) is rare in men aged <50 years (early-onset). A well-designed nomogram for prognosis prediction in patients with early-onset PCa has not been studied. Here, we tried to establish nomogram models of overall survival (OS) and cancer-specific survival (CSS) in patients with early-onset PCa. The clinical variables of patients diagnosed with early-onset PCa between 2004 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation groups at a ratio of 7:3. Multivariate Cox regression analyses were used to select prognostic factors associated with OS or CSS, followed by the construction and validation of nomograms. We enrolled 8259 patients with early-onset PCa. New nomograms were established and showed good discriminative abilities. Finally, ROC curve analysis demonstrated that these nomograms were superior to the TNM stage and Gleason score in predicting both OS and CSS for patients with early-onset PCa. This is the first study to establish nomograms with effective and high accuracy for prognosis in patients with early-onset PCa. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the prognostic ability of blood urea nitrogen (BUN) to serum albumin ratio (BAR) to predict in-hospital mortality in patients with lung cancer in the intensive care unit (ICU). Methods: Medical Information Mart for Intensive Care IV (MIMIC-IV v1.0) database was used to identify patients who were diagnosed with lung cancer. The primary outcome was in-hospital mortality. Multivariate COX regression was used to investigate the association between BAR and in-hospital mortality and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were also used to ensure the robustness of our findings. eICU-CRD database (validation cohort) was also applied to validate our findings. Results: The optimal cut-off value for BAR was 6.8mg/g. Among 1202 patients who were diagnosed with lung cancer, 287 high-BAR group (≥ 6.8mg/g) patients and 287 low-BAR group (< 6.8mg/g) patients, who had similar propensity scores were included in this study. After matching, the high-BAR group had significantly higher in-hospital mortality (hazard ratio, HR, 2.24, 95% confidence index, 95% CI, 1.57– 3.19, P< 0.001) even after adjustment for confounding factors. Moreover, the performance of BAR was superior to that of BUN and serum albumin alone and could add net benefit in predicting in-hospital mortality. Those results were further confirmed in the validation cohort. Conclusion: As an easily accessible and cost-effective parameter, BAR could serve as a good prognostic predictor for lung cancer patients in ICU. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the clinicopathological characteristics presented in 9 cases of gastric calcifying fibrous tumor (CFT), and investigate the expressions and clinical implications of G protein-coupled estrogen receptor (GPER), estrogen receptor (ER) and vimentin in gastric CFTs. The clinical and pathological information of 9 patients with CFTs was investigated retrospectively. Subsequently, the expression of GPER, ER and vimentin were examined using immunohistochemistry, and a literature search for gastric CFT was conducted. The 9 patients were 40–71 years old with a mean age of 52.22 years, including 6 female and 3 male patients. Pathological features included dense hyalinized collagen fibers with a psammomatous body or dystrophic calcification, and the infiltration of scattered lymphocytes and plasma cells. Immunohistochemically, all cases expressed vimentin and GPER, whereas ER expression was negative. Using a database research, 25 studies regarding gastric CFT were identified, including 48 cases with a sex ratio (female:male) of 1.4:1. In addition, the number of female patients was twice the number of male patients in patients <50 years old, whereas the number was almost equal between women and men ≥50 years of age. Gastric CFT is a benign lesion with a good prognosis and a predilection for female patients, particularly premenopausal women. Estrogen may serve a role in this female predominance, and this may be mediated by GPER rather than ER. [ABSTRACT FROM AUTHOR]

Background: Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Materials and Methods: Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Results: Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). Conclusion: This meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor, and is the second highest cause of cancer-associated mortality, behind lung carcinoma. It is urgent to identify novel genes that can be used to confirm the diagnosis and prognosis of patients with HCC. The present study aimed to investigate the expression pattern of phosphatidylinositol glycan anchor biosynthesis class C (PIGC) in HCC and assess its clinical prognostic significance. Bioinformatics analyses were used to investigate PIGC mRNA expression levels in HCC and adjacent non-cancerous tissue samples. Furthermore, the present study detected the expression levels of PIGC protein in HCC and matched normal tissue samples via immunohistochemistry, and evaluated the prognostic significance of PIGC protein in HCC. The levels of PIGC mRNA and protein were found to be significantly higher in tissue from patients with HCC compared with non-cancerous liver tissue. The survival analysis showed that the expression levels of PIGC mRNA or protein were associated with the survival of patients with HCC. PIGC protein expression was significantly associated with Tumor-Node-Metastasis stage. A negative correlation between PIGC DNA methylation and mRNA expression was observed (Spearman r=−0.453). PIGC is an oncogene that is negatively regulated by DNA methylation, and high levels of PIGC mRNA or protein may predict an unfavorable prognosis in patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Medication adherence to inhaler therapy is pivotal for optimizing the management of COPD. Individuals with COPD often have suboptimal adherence behaviors to inhaler therapy. Illness perception and beliefs about medicines have been proved to be associated with medication adherence. Nevertheless, the influence of illness perception and medication beliefs on adherence to inhaler therapy among elderly individuals with COPD in China remains unclear., Methods: A cross-sectional study was conducted in 252 elderly subjects with COPD in China from June 2022-September 2023. The Test of Adherence to Inhalers, the Brief Illness Perception Questionnaire, and the Belief About Medicines Questionnaire (BMQ) were utilized. Spearman correlations, regression analysis, and parallel mediation analysis were employed to assess the correlations and mediating effects among beliefs about medicines, illness perception, and medication adherence to inhaler therapy., Results: Medication adherence to inhaler therapy exhibited a negative correlation with concerns beliefs, while showing positive correlations with illness perception, necessity beliefs, and total BMQ scores. Mediating effects of concerns beliefs and necessity beliefs were observed in the relationship between perception of illness and medication adherence to inhaler therapy., Conclusions: This study suggests that essential interventions targeting beliefs about medicines in elderly individuals with COPD should be implemented to optimize the level of their inhaler adherence, particularly in those with low levels of necessity beliefs or high levels of concerns beliefs., (Copyright © 2024 by Daedalus Enterprises.)

Gastric cancer (GC) is a prevalent malignancy affecting the digestive system, and it is the second leading cause of cancer-related mortality worldwide. Immunotherapy presents a potential lifeline for patients with advanced gastric cancer, emphasizing the need to find new molecular targets that improve the response to immunotherapy. In our research, we conducted a comprehensive bioinformatic analysis to investigate the expression profiles of apolipoprotein E (APOE) transcription. Subsequently, we examined the correlation between APOE transcription and the prognosis of GC patients. Additionally, we evaluated the connection between APOE transcription and immune cells abundance. To validate our findings, we conducted immunohistochemistry experiment to ascertain the level of APOE protein in GC patients and assessed its prognostic role in a cohort of 97 GC individuals. Our results revealed that APOE is increased in GC tissues, and APOE displays diagnostic potential in distinguishing GC from normal tissues. Notably, upregulated APOE expression in GC patients is associated with unfavorable overall survival. Differential APOE expression was further observed across different immune subtypes of GC, indicating its involvement in immune cell activation and infiltration. Moreover, we detected increased APOE protein expression in GC tissues, which exhibited a strong correlation with poor survival outcomes. In light of these findings, APOE has become a crucial prognostic molecular with immunomodulatory function in GC. These results underscore the significance of APOE across various cancer types, including GC, and provide valuable insights into its role from both a bioinformatics and clinical perspective.

Calpains2 (CAPN2) is a calcium-dependent, non-lysosomal cysteine protease that plays critical roles in normal cellular functions and pathological processes, including tumorigenesis, cancer progression, and metastasis. However, the role and underlying regulatory mechanisms of CAPN2 in pancreatic cancer (PC) are still unknown. We found that CAPN2 is highly expressed in PC tissues and associated with poor PC prognosis by using The Cancer Genome Atlas (TCGA) datasets, Gene Expression Omnibus (GEO) datasets, and PC tissue arrays. CAPN2 downregulation significantly inhibited cell proliferation, migration, and invasion and regulated Wnt/β-catenin signaling pathway-mediated epithelial-mesenchymal transition (EMT) in PC cells. Our findings highlight the significance of CAPN2 in tumor regression and, thus, indicate that CAPN2 could be a promising target for PC treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Yang, Song, Wang and Dong.)

BACKGROUND The results of previous studies that evaluated the association between pretreatment blood platelet-to-lymphocyte ratio (PLR) and clinical outcomes and chemosensitivity in patients with advanced gastric cancer are inconsistent. Therefore, this study was designed to investigate the association between pretreatment blood PLR and clinical outcomes and chemosensitivity in advanced gastric cancer patients. MATERIAL AND METHODS We performed a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library up to Mar 9, 2021. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were pooled for meta-analysis. The quality of the included studies was measured by the Newcastle-Ottawa Quality Assessment Scale. RESULTS We included 17 studies comprising 3499 patients with advanced GC in this meta-analysis. Pooled results demonstrated that high PLR was correlated with poor OS (HR=1.429, 95% CI=1.246-1.639, P<0.001) and DFS (HR=1.47, 95% CI=1.14-1.88, P=0.003) compared with low PLR in patients with advanced GC. Moreover, high PLR was associated with a lower response to chemotherapy in patients with advanced GC (OR=1.395, 95% CI=1.056-1.841, P=0.019). However, there was no significant correlation between PLR and clinicopathological features. CONCLUSIONS This meta-analysis suggests that high PLR is a risk factor for unfavorable OS, DFS, and chemosensitivity in patients with advanced GC.

Purpose: Liver cancer or hepatocellular carcinoma (HCC) is considered as one of the most frequent malignancies with significantly high morbidity and mortality across the globe. MicroRNAs (miRs) are regarded as important regulators of liver cancer formation and its development. However, the full biochemical mechanism of their role is still very less understood. The main objective of the current research work was to examine the role of miR-16/cyclin-B1 axis in liver cancer regulation and how this pathway along with liver cancer migration and invasion are targeted by zingiberene molecule., Methods: Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-16 expression in HCC cell lines. Western blotting was performed to evaluate the expression of the miR-16 target genes. Effects on cell migration and invasion were evaluated by in vitro wound healing assay and transwell Matrigel assay, respectively. Effects of zingiberene on HCC cell viability were evaluated by MTT assay., Results: Zingiberene treatment led to downregulation of miR-16 in HepG2 human hepatocellular carcinoma cells, accompanied by induction of G0/G1 cell cycle arrest targeting cyclin B1 as direct target. These effects were also accompanied by inhibition of cell migration and invasion, indicating that miR-16 can have a significant role as liver cancer suppressor after zingiberene treatment. Luciferase reporter assay confirmed that miR-16, which was one of HCC downregulated miRs, directly targeted Cyclin B1 in HCC cells., Conclusion: The current study indicates miR-16/cyclin B1 axis might have significant applications as a therapeutic target for patients with liver cancer.

Purpose: Gastric carcinoma is the fourth leading cause of cancer-related morbidity throughout the globe. There are limited clinical therapies for gastric cancer due to lack of effective drugs and ambiguity in molecular mechanisms. As such there is a pressing need for novel and effective anticancer drugs for gastric cancer. The main aim of the current research work was to investigate the anticancer effects of Lanostane natural product in MKN-45 human gastric cancer cells along with evaluating its effects on cell autophagy, apoptosis, and m-TOR/PI3K/AKT signalling pathway., Methods: MTT cytotoxicity assay was used to evaluate cell viability of MKN-45 human gastric cancer cells. Apoptosis was evaluated by fluorescence microscopy using Hoechst 33258 and Annexin-V/propidium iodide (PI) assay using flow cytometry. Autophagy was evaluated by transmission electron microscopy (TEM) and western blot method. Effects on m-TOR/PI3K/AKT related protein expression were evaluated by western blot method., Results: Lanostane molecule led to substantial and dose-dependent growth inhibitory effects onMKN-45 human gastric cancer cells. Clonogenic assay showed significant decrease in MKN-45 cell colonies. Hoechst 33258 and annexin V/PI revealed that lanostane induced dominant apoptotic effects in these cells and exhibited dose-dependence. TEM revealed that lanostane induced autophagy in MKN-45 cells by forming autophagosomes and autophagic vacuoles. Lanostane also targeted m-TOR/PI3K/AKT signalling pathway by altering the expression of some key proteins., Conclusion: Lanostane displayed strong anticancer effects in MKN-45 human gastric cancer cells by triggering apoptosis and autophagy and targeting m-TOR/PI3K/AKT signalling pathway.

Previous studies investigated the prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with biliary tract cancer (BTC); however, the results remained controversial. Therefore, we conducted the current meta-analysis with the aim of clarifying the association between PD-L1 expression and prognosis as well as with several important clinicopathological features of BTC. We searched PubMed, Embase, and Web of Science for relevant studies. Studies that detected PD-L1 expression in tumor cells by using immunohistochemistry (IHC) were selected. Pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlations. In total, 15 independent studies with 1,776 patients were included in this meta-analysis. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival (n=15, HR=1.79, 95% CI=1.55-2.07, p<0.001). The correlation between PD-L1 expression and disease-free survival was not significant (n=6, HR=1.38, 95% CI=1.00-1.91, p=0.051). In addition, no significant correlation was observed between PD-L1 expression and clinical features in patients with BTC. Our study results showed that PD-L1 expression could play a pivotal role as an effective factor of poor prognosis in patients with BTC.

Hepatitis B infection is a major global health problem and a primary cause of hepatocellular carcinoma (HCC). While various antiviral treatments have been explored, there is not yet a reliable method for preventing the progression of chronic hepatitis B infection into HCC. Hepatitis B virus X protein (HBx) plays a major role in viral replication, chronic inflammation and the pathogenicity of chronic liver disease. Modulation of purinergic receptors using their specific agonists has become a popular new strategy for modifying disease processes. In the present study, we investigated the involvement of the P2Y 11 receptor using its specific antagonist NF157 in some key aspects of HBx-induced liver disease in human MIHA hepatocytes, including mitochondrial dysfunction due to compromised mitochondrial membrane potential (MMP), oxidative stress resulting from overproduction of reactive oxygen species (ROS) and decreased antioxidant glutathione (GSH), production of proinflammatory cytokines and chemokines such as interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and chemokine (C-X-C motif) ligand 2 (CXCL2), as well as activation of cellular signaling pathways including the p38/mitogen-activated protein kinase (p38/MAPK) and nuclear factor-κB (NF-κB) pathways. Our findings present a novel new strategy for the treatment and prevention of chronic liver infection and subsequent morbidities induced by HBx via specific antagonism of the P2Y 11 purinergic receptor., Competing Interests: None.

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) has previously been demonstrated to be associated with the malignant transformation of numerous types of human cancer. The aim of the present study was to investigate the effect of EBP50 overexpression on pancreatic cancer and the underlying mechanism. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of EBP50 in human pancreatic cancer tissue specimens. Furthermore, pBK-CMV-HA-EBP50 and the pBK-CMV-HA vectors were transfected into pancreatic cancer cells and the effect of EBP50 upregulation on the proliferation and invasion of the cells was investigated. In addition, the effect of EBP50 overexpression on β-catenin and E-cadherin expression was evaluated. The results revealed that overexpression of EBP50 suppressed cell growth and invasion in two human pancreatic cancer cell lines. Overexpression of EBP50 also suppressed β-catenin expression and increased E-cadherin expression. Thus, the present study demonstrated that EBP50 inhibits pancreatic cancer cell growth and invasion through targeting the β-catenin/E-cadherin pathway. The results suggest that EBP50 may function as a potential tumor suppressor and thus may serve as a potential therapeutic target.

The major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism has been implicated in susceptibility to cancer. However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the MICA-TM polymorphisms and cancer risk. All eligible case-control studies published up to August 20, 2014 were identified by searching PubMed, Web of Science, CNKI and Wanfang databases. The cancer risk associated with the MICA polymorphism was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. 21 studies from 19 publications with 3620 cases and 4903 controls were included. Overall, no significant associations between the MICA-TM polymorphism and cancer risk were found (A4 allele: OR = 0.97, 95% CI: 0.88-1.07; A5 allele: OR = 0.91, 95% CI: 0.81-1.04; A5.1 allele: OR = 1.03, 95% CI: 0.89-1.18; A6 allele: OR = 1.05, 95% CI: 0.95-1.15; A9 allele: OR = 0.96, 95% CI: 0.80-1.14; A10 allele: OR = 0.88, 95% CI: 0.43-1.79; del: OR = 2.50, 95% CI: 0.73-8.58; A7 allele: OR = 0.93, 95% CI: 0.43-2.00). When stratified by ethnicity, similar results were observed among Asians; however, there were significant association in Caucasian population for A5 (OR = 0.77, 95% CI: 0.68-0.87) and A9 allele (OR = 0.75, 95% CI: 0.66-0.85). This meta-analysis suggests that the MICA-TM A5 and A9 alleles may be an important protective factor for cancer in Caucasian populations.

Increasing evidence has demonstrated that ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is involved in the malignant transformation of numerous human cancers. The present study investigated the involvement of EBP50 overexpression in the tumorigenicity of pancreatic cancer (PC). The results revealed that overexpression of EBP50 suppressed cell growth, promoted cell apoptosis and arrested G1-to-S phase progression in two human PC cell lines. Overexpression of EBP50 also suppressed B-cell lymphoma 2 (Bcl-2) expression. Furthermore, nude mouse tumor xenograft models were established by the subcutaneous injection of cell lines stably transfected with an EBP50-expressing plasmid. The in vivo data indicated that overexpression of EBP50 inhibited the growth of the PC tumors and induced cell apoptosis. Thus, the present study demonstrated that EBP50 overexpression induces growth inhibition and apoptosis in PC by decreasing Bcl-2 expression. The results suggest that EBP50 may function as a potential tumor suppressor in vivo and in vitro .