Background: Metabolic-associated fatty liver disease (MAFLD) is a new term of nonalcoholic fatty liver disease (NAFLD), with newly proposed diagnostic criteria. The applicability of common noninvasive testing for screening NAFLD is unclear for the detection of MAFLD and requires reevaluation. We aimed to validate the effectiveness of traditional NAFLD-related steatosis indices for diagnosing MAFLD and to determine the optimal cutoff values as well as compare their accuracy between NAFLD and MAFLD diagnosis. Methods: This study enrolled 1866 participants from the National Health and Nutrition Examination Survey (NHANES) database (2017–2018). The diagnostic performances of fatty liver index (FLI), Framingham Steatosis Index (FSI), Zhejiang University index (ZJU), lipid accumulation product (LAP), hepatitis steatosis index (HSI) and visceral adiposity index (VAI) were evaluated using the area under the receiver operator characteristic (AUROC) curve and the optimal cutoff points were calculated according to maximum Youden’s index. Results: FLI had the highest AUROC (0.840) for predicting MAFLD in the whole population, with a cutoff value of 56.93. The AUROCs of FLI, FSI, ZJU, LAP, HSI and VAI for predicting MAFLD/NAFLD were 0.840/0.812, 0.833/0.811, 0.826/0.811, 0.826/0.799, 0.814/0.803 and 0.747/0.729, respectively. The AUROC values of all indices decreased in the subgroup of the population with overweight or diabetes. Conclusion: The NAFLD-related scores would be equally useful to screen MAFLD and seemed to be more compatible with MAFLD. The FLI was optimal in both MAFLD and NAFLD diagnoses. However, a new predictive indicator suitable for various characteristics of the population is worth further development in the future.

Background. Inflammation plays an important role in the development of tumors. Several serum based-markers and ratios have been investigated for their prognostic value in pancreatic cancer. However, the prognostic value of the neutrophil-to-monocyte ratio (NMR) and platelet-to-white blood cell ratio (PWR) for patients with pancreatic cancer has scarcely been investigated. Methods. From October 2013 to November 2018, a retrospective cohort study was performed on 269 pancreatic cancer patients without treatment. Receiver operating characteristic curves were generated, and areas under the curve were compared for the evaluation of the discriminatory ability of inflammation-based prognostic scoring systems. Kaplan-Meier curves and the Cox proportional hazard model were employed to analyze the relationships among NMR, PWR, and overall survival (OS). Results. The optimal cutoff values of NMR and PWR were 48 and 6, respectively. In univariate analysis, the survival time of and was shorter than that of and in patients with pancreatic cancer ( ). In Cox univariate and multivariate analyses, NMR (hazard ratio (HR), 9.095; 95% confidence interval (CI), 3.64–22.72; ) and PWR (HR, 8.230; 95% CI, 3.32–20.43; ) were significantly correlated with OS. Conclusions. The current study demonstrated that NMR and PWR may serve as novel and promising inflammatory prognostic scores for patients with pancreatic cancer. Elevated NMR (>48) and depressed PWR (<6) were independently associated with poor prognosis in patients with pancreatic cancer.

Background: Alantolactone (AL) is a natural compound extracted from the roots of Inula Helenium L, which exerts an anti-tumor effect in a variety of cancer cell lines; however, its effect on esophageal cancer, a common malignancy with poor prognosis, remains unclear. Therefore, we aim to evaluate the effect of AL on esophageal cancer and to explore its underlying mechanism. Objective: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism. Methods: The effect of AL on the proliferation and apoptosis of esophageal cancer cells was detected by MTT assay, colony formation assay, crystal violet assay, flow cytometry and hoechst apoptosis staining. The wound healing and Transwell invasion assay were performed to examine the effect of AL on the migration and invasion of esophageal cancer cells. Luciferase reporter system and Western blot were used to study the anti-tumor mechanism of AL on esophageal cancer cells. The subcutaneous murine xenograft model was employed to verify the effects of AL on esophageal cancer cells. Results: MTT assay, colony formation assay and crystal violet assay found that AL inhibited the growth of esophageal cancer cells. Hoechst staining and flow cytometry analysis showed that AL induced apoptosis in esophageal cancer through mitochondrial pathway. Transwell assay and wound healing assays showed that AL inhibited the metastasis and invasion of esophageal cancer cells. Wnt/ β-catenin signaling may contribute to the mechanism of the inhibition. The anti-tumor effect of AL on esophageal cancer cells was validated on murine xenograft model. Conclusion: Our data indicate that AL inhibits proliferation, migration, and invasion of esophageal cancer cells, and promote apoptosis of esophageal cancer cells through the Wnt/β-catenin signaling pathway.

Colorectal cancer (CRC) resistance to 5-fluorouracil (5-FU), primarily driven by cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT), remains a major clinical challenge, necessitating novel therapeutic strategies. This study aims to evaluate the therapeutic potential of pentagalloyl glucose (PGG), a bioactive compound derived from Bouea macrophylla seeds, in overcoming 5-FU resistance in CRC. Anti-tumor effects of PGG were investigated using two- and three-dimensional (2D and 3D) cell culture models and subcutaneous xenograft and metastatic mouse models. Transcriptome sequencing, western blotting, and pharmacological inhibitors were employed to elucidate the underlying molecular mechanisms. PGG demonstrated potent anti-CSC activity; suppressed EMT-driven invasion and metastasis; and induced apoptosis in 2D monolayers, 3D spheroid models, and xenograft tumor models. Mechanistically, PGG selectively inhibited the JAK1/JAK3-STAT3 signaling pathway, considerably reducing STAT3 phosphorylation. This disruption downregulated the expression of CSC markers (CD133 and CD44), EMT regulators (N-cadherin and vimentin), and anti-apoptotic proteins (Bcl-2), effectively sensitizing 5-FU-resistant CRC to therapy. PGG inhibit dual-target of CSCs and EMT via JAK1/JAK3-STAT3 signaling pathway in 5-FU-resistant CRC, providing a novel therapeutic approach to overcome chemoresistance.

Cirrhotic patients with acute variceal hemorrhage (AVH) have high short-term mortality. Established prognostic scores are seldom applicable clinically, partially because they need external validation or contain subjective variables. We aimed to develop and validate a practical prognostic nomogram based on objective predictors to predict prognosis for cirrhotic patients with AVH. We enrolled 308 AVH patients with cirrhosis from our center as the derivation cohort to develop a new nomogram using logistic regression and validated it in cohorts of patients from Medical Information Mart for Intensive Care (MIMIC) III (n = 247) and IV (n = 302). International normalized ratio (INR), albumin (ALB) and estimated glomerular filtration rate (eGFR) were identified as predictors for inpatient mortality and a nomogram was constructed based on them. The nomogram discriminated well in both derivation and MIMIC-III/-IV validation cohorts with the area under the receiver operating characteristic curves (AUROCs) of 0.846 and 0.859/0.833, respectively and showed a better agreement between expected and observed outcomes (Hosmer-Lemeshow tests, all comparisons, P > 0.05) than other scores in all cohorts. Our nomogram had the lowest Brier scores (0.082/0.114/0.119 in training/MIMIC-III/MIMIC-IV) and highest R² (0.367/0.393/0.346 in training/MIMIC-III/MIMIC-IV) compared to the recalibrated model for end-stage liver disease (MELD), MELD-hepatic encephalopathy (MELD-HE) and cirrhosis acute gastrointestinal bleeding (CAGIB) scores in all cohorts. We developed a practical prognostic nomogram using easily verified indicators available in initial patient evaluation, which may serve as a reliable tool to accurately predict inpatient mortality for cirrhotic patients with AVH.

Central Asia has gradually become the place where terrorism broke out and the source of terrorism, and the risk of terrorist attacks is increasing. Political factors are the endogenous factors for the spread of terrorism and extremism in Central Asia. Poverty and political turmoil have given Central Asian terrorism a social foundation for the people. The return of terrorists has made the anti-terrorism situation in Central Asia extremely complicated. In the future, it is necessary to strengthen international anti-terrorism criminal judicial cooperation in order to effectively control terrorism and extremism.