Chronic low-dose deltamethrin exposure induces colon injury and aggravates DSS-induced colitis via promoting cellular senescence.

OBJECTIVE: Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism. METHODS: The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism. RESULTS: Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario. CONCLUSION: Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.

Applications of cold atmospheric plasma in immune-mediated inflammatory diseases via redox homeostasis: evidence and prospects.

As a representative technology in plasma medicine, cold atmospheric plasma (CAP) has beneficial outcomes in surface disinfection, wound repair, tissue regeneration, solid tumor therapy. Impact on immune response and inflammatory conditions was also observed in the process of CAP treatment. Relevant literatures were collected to assess efficacy and summarize possible mechanisms of the innovation. CAP mediates alteration in local immune microenvironment mainly through two ways. One is to down-regulate the expression level of several cytokines, impeding further conduction of immune or inflammatory signals. Intervening the functional phenotype of cells through different degree of oxidative stress is the other approach to manage the immune-mediated inflammatory disorders. A series of preclinical and clinical studies confirmed the therapeutic effect and side effects free of CAP. Moreover, several suggestions proposed in this manuscript might help to find directions for future investigation.

Plasma-Activated Solutions Mitigates DSS-Induced Colitis via Restoring Redox Homeostasis and Reversing Microbiota Dysbiosis.

Ulcerative colitis is a chronic disease that increases the risk of developing colorectal cancer. Conventional medications are limited by drug delivery and a weak capacity to modulate the inflammatory microenvironment. Further, gut microbiota dysbiosis caused by mucosal damage and dysregulated redox homeostasis leads to frequent recurrence. Therefore, promoting mucosal healing and restoring redox homeostasis is considered the initial step in treating ulcerative colitis. Plasma-activated solutions (PAS) are liquids rich in various reactive nitrogen species (RNS) and reactive oxygen species (ROS) and are used to treat multiple diseases. However, its effect on ulcerative colitis remains to be examined. Therefore, using a DSS-induced mice colitis model, it is found that PAS has the potential to treat colitis and prevent its recurrence by promoting intestinal mucosal repair, reducing inflammation, improving redox homeostasis, and reversing gut microbiota dysbiosis. Further, an equipment is designed for preparing PAS without using nitrogen; however, after treatment with the Nitro-free PAS, the therapeutic effect of PAS is significantly weakened or even lost, indicating that RNS may be the main mediator by which PAS exerts its therapeutic effects. Overall, this study demonstrates the treatment of ulcerative colitis as a novel application of PAS.

Chronic exposure to low-dose deltamethrin can lead to colon tissue injury through PRDX1 inactivation-induced mitochondrial oxidative stress injury and gut microbial dysbiosis.

OBJECTIVE: To date, it is unclear whether deltamethrin (DLM) intake causes damage to colon tissue. Hence, in this study, we aimed to clarify the effect of long-term exposure to low-dose DLM on colon tissues, and its potential mechanisms. METHODS: Mice were treated with DLM (0.2 mg/kg/day) or DLM combined with N-acetyl-l-cysteine (NAC) (50 mg/kg/day) for 8 weeks. Human colon cancer cells (HCT-116) were treated with DLM (0, 25, 50, or 100 µM), NAC (2 mM), or overexpression plasmids targeting peroxiredoxin 1 (PRDX1) for 48 h. DLM was detected using a DLM rapid detection card. Colon injury was evaluated using haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was determined using immunofluorescence staining (IF), western blotting (WB) and flow cytometry (FC) assays. MitoTracker, JC-1, and glutathione (GSH) detection were used to detect mitochondrial oxidative stress. Intestinal flora were identified by 16 S rDNA sequencing. RESULTS: DLM accumulation was detected in the colon tissue and faeces of mice following long-term intragastric administration. Interestingly, our results showed that, even at a low dose, long-term intake of DLM resulted in severe weight loss and decreased the disease activity index scores and colon length. The results of IF, WB, and FC showed that DLM induced apoptosis in the colon tissue and cells. MitoTracker, JC-1, and GSH assays showed that DLM increased mitochondrial stress in colonic epithelial cells. Mechanistic studies have shown that increased mitochondrial stress and apoptosis are mediated by PRDX1 inhibition. Further experiments showed that PRDX1 overexpression significantly reduced DLM-induced oxidative stress injury and apoptosis. In addition, we observed that chronic exposure to DLM altered the composition of the intestinal flora in mice, including an increase in Odoribacter and Bacteroides and a decrease in Lactobacillus. The gut microbial richness decreased after DLM exposure in mice. Supplementation with NAC both in vivo and in vitro alleviated DLM-induced oxidative stress injury, colonic epithelial cell apoptosis, and gut microbial dysbiosis. CONCLUSION: Chronic exposure to DLM, even at small doses, can cause damage to the colon tissue, which cannot be ignored. The production and use of pesticides such as DLM should be strictly regulated during agricultural production.

Clinical significance of FBXO43 in hepatocellular carcinoma and its impact on tumor cell proliferation, migration and invasion.

Background: The effects of FBXO43 on hepatocellular carcinoma (HCC) and its clinical significance have not yet been determined. This study aims to determine the clinical significance of FBXO43 in HCC and its impact on the biological functions of HCC cells. Methods: Data from TCGA database were downloaded to investigate the expression of FBXO43 in HCC and its correlation with prognosis and immune infiltration. Immunohistochemical staining images of FBXO43 in HCC were acquired from the HPA website. HCC cells (BEL-7404 and SMMC-7721) were transfected with the lentivirus targeting FBXO43 to decrease FBXO43 expression in HCC cells. Western blotting assay was conducted to evaluate the expression level of FBXO43 protein. MTT assay was used to detect the proliferation of HCC cells. The migration and invasion of HCC cells were investigated by performing scratch wound-healing and Transwell invasion assays, respectively. Results: In comparison to normal tissues, FBXO43 is overexpressed in HCC tissue, and high FBXO43 expression is linked to late T stage, TNM stage and tumor grade. Elevated FBXO43 expression is a risk factor for HCC. In patients with high FBXO43 expression, the overall survival, disease-specific survival, progression-free survival and disease-free survival are poorer. The proliferation, migration and invasion of HCC cells are significantly attenuated in FBXO43 knockdown cells. Also, TCGA data analysis reveals that FBXO43 exhibits a positive correlation with immunosuppression of HCC. Conclusion: FBXO43 is overexpressed in HCC, and is linked to late tumor stage, worse prognosis and tumor immunosuppression. FBXO43 knockdown restrains the proliferation, migration and invasion of HCC.

Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer.

The aim of this study is to evaluate the factors affecting the objective response rate (ORR) after neoadjuvant therapy of taxol plus platinum (TP) regimen combined with programmed cell death protein-1 (PD-1) inhibitors for esophageal cancer, and establish a predictive model for forecasting ORR. According to the inclusion and exclusion criteria, consecutive esophageal cancer patients who were treated in the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to February 2022 were enrolled in this study as a training cohort, while patients who were treated in the Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi'an Jiaotong University from January 2020 to December 2021 were enrolled as a validation cohort. All patients were treated with resectable locally advanced esophageal cancer and received neoadjuvant chemotherapy combined with immunotherapy. The ORR was defined as the sum of complete pathological response, major pathological response and partial pathological response. Logistic regression analysis was performed to determine the factors that might be related to the ORR of the patients after neoadjuvant therapy. The nomogram based on the result of regression analysis was established and verified to predict the ORR. In this study, 42 patients were included as training cohort and 53 patients were included as validation cohort. Chi-square analysis showed that neutrophil, platelet, platelet-to-lymphocytes ratio (PLR), systemic immune-inflammation index (SII), D-dimer and carcinoembryonic antigen (CEA) between ORR group and non-ORR group were significantly different. Logistic regression analysis showed that aspartate aminotransferase (AST), D-dimer and CEA were independent predictors of ORR after neoadjuvant immunotherapy. Finally, a nomogram was established based on AST, D-dimer and CEA. Internal validation and external validation revealed that the nomogram had a good ability to predict ORR after neoadjuvant immunotherapy. In conclusion, AST, D-dimer and CEA were the independent predictors of ORR after neoadjuvant immunotherapy. The nomogram based on these three indicators showed a good predictive ability.

A nomogram based on platelet-to-lymphocyte ratio for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy.

OBJECTIVE: To investigate the role of platelet-to-lymphocyte ratio (PLR) in complete pathological response (pCR) of breast cancer (BC) patients after neoadjuvant chemotherapy (NAC), as well as to establish and validate a nomogram for predicting pCR. METHODS: BC patients diagnosed and treated in the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to June 2022 were included. The correlation between pCR and clinicopathological characteristics was analyzed by Chi-square test. Logistic regression analysis was performed to evaluate the factors that might affect pCR. Based on the results of regression analysis, a nomogram for predicting pCR was established and validated. RESULTS: A total of 112 BC patients were included in this study. 50.89% of the patients acquired pCR after NAC. Chi-square test showed that PLR was significantly correlated with pCR (X2 = 18.878, P < 0.001). And the PLR before NAC in pCR group was lower than that in Non-pCR group (t = 3.290, P = 0.001). Logistic regression analysis suggested that white blood cell (WBC) [odds ratio (OR): 0.19, 95% confidence interval (CI): 0.04-0.85, P = 0.030)], platelet (PLT) (OR: 0.19, 95%CI: 0.04-0.85, P = 0.030), PLR (OR: 0.18, 95%CI: 0.04-0.90, P = 0.036) and tumor grade (OR: 9.24, 95%CI: 1.89-45.07, P = 0.006) were independent predictors of pCR after NAC. A nomogram prediction model based on WBC, PLR, PLR and tumor grade showed a good predictive ability. CONCLUSION: PLR, PLT, WBC and tumor grade were independent predictors of pCR in BC patients after NAC. The nomogram based on the above positive factors showed a good predictive ability.

The comparison of long-term oncological outcomes and complications after proximal gastrectomy with double tract reconstruction versus total gastrectomy for proximal gastric cancer.

BACKGROUND: Conventional methods for treating patients with proximal gastric cancer (PGC) include proximal gastrectomy (PG) and total gastrectomy (TG) and such methods have become challenging due to double tract reconstruction (DTR). However, the clinical outcomes remain unclear. This study was performed with the aim of verifying that PG-DTR was beneficial in terms of reducing the incidence of postoperative complications and improving the prognosis. METHODS: The PGC patient cohort was retrospectively grouped into the PG-DTR and TG groups. Clinicopathological features, complications, and survival data were compared between the two groups. RESULTS: A total of 388 patients were included in the analyses. Patients who were subjected to TG tended to have more severe gastroesophageal reflux (GR) (P = 0.041), anemia (P = 0.007), and hypoalbuminemia (P < 0.001). Overall survival rates, regardless of clinical stage, were significantly different between the PG-DTR and TG groups (all P < 0.05). The multivariate Cox regression analysis confirmed that surgical procedure, tumor size, infiltration depth, lymph node metastasis, differentiation, and age were independent risk factors. The patients were likely to benefit from PG-DTR (all HR > 1 and P < 0.05). However, no significant differences were observed in the risks of GR, anemia, and hypoalbuminemia (all P > 0.05). Moreover, the nomogram derived from significant parameters showed great calibration and discrimination ability and significant clinical benefit. CONCLUSIONS: The patients who underwent PG-DTR had a favorable prognosis. The risk of postoperative complications, such as severe GR, anemia, and hypoalbuminemia, was lower in PG-DTR than in TG. Thus, PG-DTR is more beneficial for patients with PGC and may be a valuable and promising surgical procedure.

[Corrigendum] METTL3­mediated m6A modification of Bcl­2 mRNA promotes non­small cell lung cancer progression.

Subsequently to the publication of the above paper, the authors have realized, upon reorganizing all their original data, that errors were made during the assembly of the images in Fig. 5 on p. 8. Specifically, in Fig. 5E, the images intended to represent the 'METTL3 sh­METTL3' and 'Bcl­2 sg­METTL3' immuno-histochemistry staining experiments were selected incorrectly. The revised version of Fig. 5, showing the correctly assembled data panels for the 'METTL3 sh­METTL3' and 'Bcl­2 sg­METTL3' experiments in Fig. 5E, is shown on the next page. The authors sincerely apologize for the errors that were inadvertently introduced during the preparation of this Figure, thank the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and regret any inconvenience that these errors may have caused to the readership. [Oncology Reports 46: 163, 2021; DOI: 10.3892/or.2021.8114].

CircTADA2A up-regulates MAPK8 by targeting MiR-214-3p and recruiting EIF4A3 to promote the invasion and migration of non-small cell lung cancer cells.

BACKGROUND: Non-small cell lung cancer (NSCLC) occupies 87% of all lung cancer cases. Due to delayed diagnosis, the prognosis of NSCLC is unfavorable. To improve the survival of patients with NSCLC, more effective therapeutic targets urgently need to be identified. Recently, circular RNAs (circRNAs) have been revealed to play a crucial role in NSCLC progression. PURPOSE: This research focused on the influence of circTADA2A on the malignant phenotype of NSCLC cells and its in-depth regulatory mechanisms. METHODS: RT-qPCR and western blot assays were done to examine the level of gene/protein of interest. Wound healing and transwell assays were conducted to monitor the migration and invasion of NSCLC cells. Bioinformatics tools and mechanistic assays were utilized to delve into the underlying mechanism of circTADA2A in NSCLC cells. RESULTS: The results demonstrated that circTADA2A presented a high expression in NSCLC. CircTADA2A knockdown was revealed to hamper migration and invasion of NSCLC cells. Mechanistically, circTADA2A elevated MAPK8 expression through sequestering miR-214-3p and recruiting EIF4A3. CONCLUSION: CircTADA2A enhances MAPK8 expression by serving as a miR-214-3p sponge and EIF4A3 decoy, consequently promoting invasion and migration of NSCLC cells.

D-dimer, a predictor of bad outcome in gastric cancer patients undergoing radical resection.

As a marker of hypercoagulability, plasma D-dimer is associated with progression of many cancers but remains controversial in gastric cancer (GC). We aim to investigate the predictive value of D-dimer for postoperative outcomes after radical gastrectomy of GC patients. We enrolled 903 consecutive patients with GC who underwent radical gastrectomy and the clinicopathological characteristics were compared. Risk factors for overall survival (OS) and disease-free survival (DFS) were determined using multivariate cox regression analysis. We also compared the survival difference based on Kaplan-Meier method after a one-to-one propensity score matching (PSM). Patients with elevated D-dimer had older age (p < 0.001), advanced TNM stage (p < 0.001), larger tumor size (p = 0.005), lower 5-year OS rate (32.8% vs 62.6%, p < 0.001) and DFS (29% vs 59.6%, p < 0.001). In multivariate analysis, elevated D-dimer was independently associated with shorter OS [hazard ratio (HR): 1.633, 95% confidence interval (CI) 1.178-2.264, p = 0.003] and DFS (HR: 1.58, 95% CI 1.151-2.169, P = 0.005). After PSM, the 5-year OS rate of patients with elevated D-dimer was still significantly lower than matched group (32.8% vs 40.6%, p = 0.005), so was DFS (29% vs 36.6%, p = 0.008). Preoperative elevated D-dimer is an independent risk factor for GC patients undergoing curative gastrectomy.

Harlequin syndrome induced by intraspinal analgesia in patients with advanced cancer: a case report.

Background: The Harlequin syndrome is an idiopathic, autonomic disorder. It typically presents with unilateral sweating and flushing of the face. It could be caused not only by autonomic dysfunction or space-occupying central neuropathy, but by some clinical interventions as well. Although iatrogenic Harlequin syndrome is rare, clinicians should be aware of this condition to diagnose correctly and provide suitable assistance. Case Description: Here we report a case of iatrogenic Harlequin syndrome. The unique part of this case is that this patient presented with successive presentations of Harlequin syndrome on different sides of the body. The patient was a 30-40-year-old woman who had flushing and sweating on one side of the face after intraspinal analgesia. This symptom disappeared on its own after a period of persistence, and reappeared several days later after increasing the dose of the drug injected into the epidural cavity. Interestingly, the second blush appeared on the other side of the patient's face. Conclusions: Triggered by intraspinal analgesia and manifested in different body parts, Harlequin syndrome is proven here to be derived from iatrogenic stimuli. We believe that the different distribution states of analgesic drugs after entering the spinal canal can promote Harlequin syndrome to manifest in different body parts.

GASP1 enhances malignant phenotypes of breast cancer cells and decreases their response to paclitaxel by forming a vicious cycle with IGF1/IGF1R signaling pathway.

There is a potential correlation between G-protein-coupled receptor-associated sorting protein 1 (GASP1) and breast tumorigenesis. However, its biological function and underlying molecular mechanism in breast cancer have not been clearly delineated. Here, we demonstrated that GASP1 was highly expressed in breast cancers, and patients harboring altered GASP1 showed a worse prognosis than those with wild-type GASP1. Functional studies showed that GASP1 knockout significantly suppressed malignant properties of breast cancer cells, such as inhibition of cell proliferation, colony formation, migration, invasion and xenograft tumor growth in nude mice as well as induction of G1-phase cell cycle arrest, and vice versa. Mechanistically, GASP1 inhibited proteasomal degradation of insulin-like growth factor 1 receptor (IGF1R) by competitively binding to IGF1R with ubiquitin E3 ligase MDM2, thereby activating its downstream signaling pathways such as NF-κB, PI3K/AKT, and MAPK/ERK pathways given their critical roles in breast tumorigenesis and progression. IGF1, in turn, stimulated GASP1 expression by activating the PI3K/AKT pathway, forming a vicious cycle propelling the malignant progression of breast cancer. Besides, we found that GASP1 knockout obviously improved the response of breast cancer cells to paclitaxel. Collectively, this study demonstrates that GASP1 enhances malignant behaviors of breast cancer cells and decreases their cellular response to paclitaxel by interacting with and stabilizing IGF1R, and suggests that it may serve as a valuable prognostic factor and potential therapeutic target in breast cancer.

Advanced lung cancer inflammation index (ALI) predicts prognosis of patients with gastric cancer after surgical resection.

INTRODUCTION: Advanced lung cancer inflammation index (ALI) has been implicated in the prognosis of many types of tumors. But few studies elucidate its role in gastric cancer (GC). MATERIALS AND METHODS: We consecutively recruited 615 GC patients who underwent radical gastrectomy. Patients were grouped according to ALI status. Risk factors for overall survival (OS) and disease-free survival (DFS) in overall and sex-stratified cohorts were determined using multivariate cox regression analysis. We also compared survival differences between the two groups after one-to-one propensity score matching (PSM). RESULTS: Patients with low ALI showed larger tumor size, more advanced TNM staging, shorter OS (median: 37 vs 42 months) and DFS (median: 37 vs 42 months) (all P < 0.001). Multivariate analysis showed that elevated ALI was independently associated with longer OS and DFS. After stratification by sex, low ALI was an independent risk factor for OS and DFS in male patients but not in female patients. But our further PSM analysis showed prognostic value of ALI in both male and female subgroups. CONCLUSION: Preoperative ALI is an independent prognostic factor for GC patients undergoing curative gastrectomy.

Therapeutic Effects of Cold Atmospheric Plasma on Solid Tumor.

Cancer is a devastating disease, and there is no particularly effective treatment at present. Recently, a new treatment, cold atmospheric plasma (CAP), has been proposed. At present, CAP is confirmed to have selective killing effect on tumor by many studies in vitro and in vivo. A targeted literature search was carried out on the study of cold atmospheric plasma. Through analysis and screening, a narrative review approach was selected to describe therapeutic effects of cold atmospheric plasma on solid tumor. According to the recent studies on plasma, some hypothetical therapeutic schemes of CAP are proposed in this paper. The killing mechanism of CAP on solid tumor is expounded in terms of the selectivity of CAP to tumor, the effects of CAP on cells, tumor microenvironment (TME) and immune system. CAP has many effects on solid tumors, and these effects are dose-dependent. The effects of optimal doses of CAP on solid tumors include killing tumor cells, inhibiting non-malignant cells and ECM in TME, affecting the communication between tumor cells, and inducing immunogenic death of tumor cells. In addition, several promising research directions of CAP are proposed in this review, which provide guidance for future research.

Predictive value of neutrophil-to-lymphocyte ratio for distant metastasis in gastric cancer patients.

As a systemic inflammatory marker, the significance of NLR in predicting tumor prognosis and early lymph node metastasis is well known, including gastric cancer (GC). However, whether NLR can reflect GC metastasis status remains to be explored. We retrospectively enrolled 1667 GC patients treated in our hospital from December 2010 to December 2018. Patients were grouped according to the presence or absence of metastases. Receiver operating characteristics (ROC) curve analysis was used to evaluate the diagnostic efficacy of markers in assessing GC metastasis. Then we conducted a joint ROC curve analysis. The effects of clinicopathological parameters on GC metastasis were assessed using multiple logistic regression analysis. 743 (44.6%) patients were diagnosed with metastatic GC. Patients with GC metastases have younger age, higher CEA, CA19-9, CA72-4 and NLR. Based on the comparison of AUC, NLR has diagnostic efficacy comparable to that of GC markers. The AUC of NLR combined with GC markers had significantly higher predicting efficacy than that without combination for assessing peritoneal metastasis (P = 0.013), osseous metastasis (P = 0.017) and hepatic metastasis (P < 0.001). In multiple logistic regression analysis, age, NLR, CEA, CA19-9 and CA72-4 were found to be independently associated with GC metastasis (all P < 0.05). NLR was a risk factor of GC metastasis. Combining CEA, CA19-9, CA72-4 and NLR could better predict metastases in GC.

Identification of a combined apoptosis and hypoxia gene signature for predicting prognosis and immune infiltration in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor worldwide. Apoptosis and hypoxia are involved in the progression of BC, but reliable biomarkers for these have not been developed. We hope to explore a gene signature that combined apoptosis and hypoxia-related genes (AHGs) to predict BC prognosis and immune infiltration. METHODS: We collected the mRNA expression profiles and clinical data information of BC patients from The Cancer Genome Atlas database. The gene signature based on AHGs was constructed using the univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analysis. The associations between risk scores, immune infiltration, and immune checkpoint gene expression were studied using single-sample gene set enrichment analysis. Besides, gene signature and independent clinicopathological characteristics were combined to establish a nomogram. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the potential functions of AHGs. RESULTS: We identified a 16-AHG signature (AGPAT1, BTBD6, EIF4EBP1, ERRFI1, FAM114A1, GRIP1, IRF2, JAK1, MAP2K6, MCTS1, NFKBIA, NFKBIZ, NUP43, PGK1, RCL1, and SGCE) that could independently predict BC prognosis. The median score of the risk model divided the patients into two subgroups. By contrast, patients in the high-risk group had poorer prognosis, less abundance of immune cell infiltration, and expression of immune checkpoint genes. The gene signature and nomogram had good predictive effects on the overall survival of BC patients. GO and KEGG analyses revealed that the differential expression of AHGs may be closely related to tumor immunity. CONCLUSION: We established and verified a 16-AHG BC signature which may help predict prognosis, assess potential immunotherapy benefits, and provide inspiration for future research on the functions and mechanisms of AHGs in BC.

Effectiveness of managing suspected metastasis using plasma D-dimer testing in gastric cancer patients.

Tumor metastasis is closely related to the coagulation system. Tumor metastasis and hypercoagulability promote each other through multiple mechanisms. However, whether coagulation indicators can reflect tumor metastasis remains to be explored. Clinical characteristics of a total of 3447 patients from three tertiary referral centers were collected. Then the diagnostic efficacy of FDP, D-dimer and GC tumor markers [Carcinoembryonic antigen (CEA), Carbohydrate antigen 19-9 (CA19-9) and Carbohydrate antigen 72-4 (CA72-4)] for GC metastases was evaluated by the receiver operating characteristic curve (ROC) analyses. Then we conducted a joint ROC curve analysis. The effects of coagulation parameters and tumor markers on gastric cancer metastasis were assessed using multiple logistic regression analysis. 2049 patients were diagnosed with primary GC, 1398 patients with metastatic GC. Based on comparison of AUC, FDP (cutoff, 1.915) had significantly higher diagnostic efficacy than fibrinogen (P<0.001), CEA (P<0.001), CA199 (P<0.001) and CA724 (P<0.001). No significant difference was observed between D-dimer (cutoff, 0.905) and FDP (P=0.158). The AUC of tumor markers combined with coagulation indexes was higher than that without combination (P<0.001). In multiple logistic regression analysis, age, smoking, D-dimer, FDP, CEA, CA19-9, CA72-4 were found to be significantly associated with GC metastasis (all P<0.001, except for smoking P=0.004). We conclude that plasma FDP and D-dimer may be novel clinical biomarkers for screening metastases of GC.

Knockdown of RSPH14 inhibits proliferation, migration, and invasion and promotes apoptosis of hepatocellular carcinoma via RelA.

BACKGROUND: High RSPH14 expression appears to be related to poor prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the possible roles of RSPH14 in the proliferation, apoptosis, and invasion of HCC cells. METHODS: The UALCAN database and Kaplan-Meier Plotter were used to evaluate the expression level and prognostic role of RSPH14 in HCC. Lentiviral vectors containing shRNA against RSPH14 were constructed to transfect the BEL-7404 and SMMC-7721 HCC cell lines. Cell proliferation was investigated by BrdU, MTT, and colony-formation assays. Apoptosis was detected using flow cytometry. Cell migration and invasion were evaluated using the scratch wound-healing and Transwell assays. Immunohistochemistry and western blot were used to determine the expression levels of the proteins. The function of RSPH14 in vivo was evaluated using a xenograft mouse model. RESULTS: The expression of RSPH14 was higher in HCC tumor tissues than in adjacent normal tissues and was closely related to unfavorable prognostic factors and poorer survival (all P < 0.05). Knockdown of RSPH14 inhibited the cell proliferation, migration, and invasion of HCC cells and promoted apoptosis (all P < 0.05). Knockdown of RSPH14 inhibited tumor growth in vivo (P < 0.05). RSPH14 knockdown led to decreased expression of RelA (NF-κBp65), CDH2, and AKT1, thereby affecting the functions of the HCC cells (all P < 0.05). RelA overexpression could abate the inhibitory effect of BEL-7404 cell proliferation caused by RSPH14 depletion. CONCLUSION: Knockdown of RSPH14 could decrease cell proliferation, migration, and invasion and increase apoptosis of HCC cells by inhibiting RelA expression. RSPH14 could be a new treatment target for HCC.

The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study.

BACKGROUND: Peptic ulcer disease (PUD) is a common digestive disorder, of which the prevalence decreased in the past few decades. However, the decreasing tendency has plateaued in recent years due to changes in risk factors associated with the etiology of PUD, such as non-steroidal anti-inflammatory drug use. In this study, we investigated the epidemiological and the sociodemographic characteristics of PUD in 204 countries and territories from 1990 to 2019 based on data from the Global Burden of Disease, Injuries and Risk Factors (GBD) Study. METHODS: Demographic characteristics and annual prevalence, incidence, mortality, disability-adjusted life years (DALYs) and age-standardized death rate (ASR) data associated with PUD were obtained and analyzed. According to the sociodemographic index (SDI), the numbers of patients, ASRs, estimated annual percentage changes and geographical distributions were assessed with a generalized linear model and presented in world maps. All evaluations of numbers and rates were calculated per 100,000 population with 95% uncertainty intervals (UIs). RESULTS: In 2019, the global prevalence of PUD was approximately 8.09 [95% UI 6.79-9.58] million, representing a 25.82% increase from 1990. The age-standardized prevalence rate was 99.40 (83.86-117.55) per 100,000 population in 2019, representing a decrease of 143.37 (120.54-170.25) per 100,000 population from 1990. The age-standardized DALY rate in 2019 was decreased by 60.64% [74.40 (68.96-81.95) per 100,000 population] compared to that in 1990. In both sexes, the numbers and ASRs of the prevalence, incidence, deaths and DALYs were higher in males than in females over 29 years. Regionally, South Asia had the highest age-standardized prevalence rate [156.62 (130.58-187.05) per 100,000 population] in 2019. A low age-standardized death rate was found in the high-income super-region. Among nations, Kiribati had the highest age-standardized prevalence rate [330.32 (286.98-379.81) per 100,000 population]. Regarding socioeconomic status, positive associations between the age-standardized prevalence, incidence, death rate, DALYs and SDI were observed globally in 2019. CONCLUSIONS: Morbidity and mortality due to PUD decreased significantly from 1990 to 2019, while a gradual upward inclination has been observed in recent 15 years, which might be associated with changes in risk factors for PUD. Attention and efforts by healthcare administrators and society are needed for PUD prevention and control.