Associations between metabolic dysfunction-associated fatty liver disease, chronic kidney disease, and abdominal obesity: a national retrospective cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) present notable health challenges, however, abdominal obesity has received scant attention despite its potential role in exacerbating these conditions. Thus, we conducted a retrospective cohort study using the National Health and Nutrition Examination Surveys III (NHANES III) of the United States from 1988 to 1994 including 9161 participants, and mortality follow-up survey in 2019. Statistical analyze including univariable and multivariable Logistic and Cox regression models, and Mediation effect analyze were applied in study after adjustment for covariates. Our findings revealed that individuals with both abdominal obesity and MAFLD were more likely to be female, older and exhibit higher prevalence of advanced liver fibrosis (7.421% vs. 2.363%, p < 0.001), type 2 diabetes mellitus (T2DM) (21.484% vs. 8.318%, p < 0.001) and CKD(30.306% vs. 16.068%, p < 0.001) compared to those with MAFLD alone. MAFLD (adjusted OR: 1.392, 95% CI 1.013-1.913, p = 0.041), abdominal obesity (adjusted OR 1.456, 95% CI 1.127-1.880, p = 0.004), abdominal obesity with MAFLD (adjusted OR 1.839, 95% CI 1.377-2.456, p < 0.001), advanced fibrosis(adjusted OR 1.756, 95% CI 1.178-2.619, p = 0.006) and T2DM (adjusted OR 2.365, 95% CI 1.758-3.183, p < 0.001) were independent risk factors of CKD. The abdominal obese MAFLD group had the highest all-cause mortality as well as mortality categorized by disease during the 30-year follow-up period. Indices for measuring abdominal obesity, such as waist circumference (WC), waist-hip ratio (WHR), and lipid accumulation product (LAP), elucidated a greater mediation effect of MAFLD on CKD compared to BMI on CKD (proportion mediation 65.23%,70.68%, 71.98%, respectively vs. 32.63%). In conclusion, the coexistence of abdominal obesity and MAFLD increases the prevalence and mortality of CKD, and abdominal obesity serves as a mediator in the association between MAFLD and CKD.

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

Development and Validation of a Prediction Model for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients Receiving Postoperative Adjuvant Transarterial Chemoembolization.

Background: Hepatocellular carcinoma (HCC) patients who are at significant risk of tumor recurrence and mortality can benefit from postoperative adjuvant transarterial chemoembolization (PA-TACE). However, the benefits of PA-TACE remain unclear. Herein, we aimed to develop a model for predicting the prognosis of HBV-related patients who undergo PA-TACE and endeavored to guide individualized clinical treatment. Methods: We included 432 HBV-related patients who underwent PA-TACE after curative resection were included. The dataset was divided into a training set (n=216) and an internal validation set (n=216). For identifying independent risk factors, the least absolute shrinkage and selection operator and univariate and multivariate Cox analyses were performed. We derived a prognostic model from the training set that was internally validated. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and risk stratification were used to evaluate the performance of the nomogram. Results: Patients undergoing PA-TACE had significantly longer overall survival (OS) than those who did not undergo PA-TACE. Age, albumin levels, macrovascular invasion, tumor size, and, stages of Barcelona Clinic Liver Cancer were identified as independent risk variables and concluded into the nomogram to predict the OS of HBV-related patients who received PA-TACE. The nomogram's C-index values OS were 0.710 and 0.652 in the training and internal validation sets, respectively. Both time-dependent AUC and the calibration curve showed good discrimination and model fitness. The risk score -0.12 was kept as the cut-off value that would accurately divide patients into high-risk and low-risk groups; furthermore, the Kaplan-Meier curve showed a high discriminative ability of the model. Conclusion: We developed a predictive model. comprising a formula and nomogram to predict the OS and provide risk stratification for HBV-related patients undergoing PA-TACE, which could contribute to suitable treatment options for this patient population.

MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA.

BACKGROUND: Our recent study found that QKI-5 regulated miRNA, miR-196b-5p, promotes non-small cell lung cancer (NSCLC) progression by directly targeting GATA6, TSPAN12 and FAS. However, the biological functions of miR-196b-5p in NSCLC progression and metastasis still remain elusive. METHODS: Cell proliferation, migration, colony formation, cell cycle assays were used to investigate cellular phenotypic changes. Quantitative real-time PCR (qRT-PCR) and western blot analyses were used to measure expressions of relative gene and protein. Interaction between QKI-5 and miR-196b-5p was determined by RNA immunoprecipitation (RIP) assay. Luciferase reporter assay was used to determine direct binding between miR-196b-5p and NFKBIA 3'-UTR. ELISA assay was used to measure secreted IL6 proteins. Mice xenograft model was used to assess the functions of NFKBIA on in vivo tumor growth. RESULTS: We demonstrated that the miR-196b-5p facilitates lung cancer cell proliferation, migration, colony formation, and cell cycle by directly targeting NFKBIA, a negative regulator of NFκB signaling. Knocking down NFKBIA increases IL6 mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth by activating NFκB signaling. The expression of NFKBIA was significantly downregulated in NSCLC tissue samples, and was negatively correlated with the expression miR-196b-5p. In addition, we found that downregulated QKI-5 expression was associated with the elevated miR-224 expression in NSCLC. CONCLUSIONS: Our findings indicated that the miR-224/QKI-5/miR-196b-5p/NFKBIA signaling pathway might play important functions in the progression of NSCLC, and suggested that targeting this pathway might be an effective therapeutic strategy in treating NSCLC.

From Conversion to Resection for Unresectable Hepatocellular Carcinoma: A Review of the Latest Strategies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

Developing and Validating an Autophagy Gene-Set-Based Prognostic Signature in Hepatocellular Carcinoma Patients.

Background: Hepatocellular carcinoma (HCC), a major type of cancer affecting the lives of people across the world, is one of many diseases whose advancement is thought to be influenced by autophagy dysfunction. Here, the prognostic significance of autophagy in HCC will be investigated. Methods: The Cancer Genome Atlas (TCGA) database was employed in this work to identify 62 differentially-expressed Autophagy-Related Genes (ARGs) in HCC patients. Functional enrichment studies revealed that autophagy played a tumor-promoting role in the advancement of HCC. Based on RNA sequencing of 116 tumor samples and 114 paracancerous tissue samples acquired from HCC patients at the Guangxi Medical University Cancer Hospital, 866 differentially expressed prognosis-related genes were identified. Using lasso regression analysis, two ARGs (BIRC5 and BAK1) linked to prognosis were discovered after intersecting the differential genes derived from the prognosis-related groups. A risk score based on ARGs was developed using a Cox proportional hazards regression model. RNA sequencing data were used to construct this model. Finally, the TCGA and The Human Protein Atlas Databases (THPA) were used to validate the clinical data of 116 HCC patients. Results: Elevated expression level of the BAK1 and BIRC5 genes is linked to poor prognosis. The two ARGs were used to calculate the risk score as follows: (0.0253*BAK1) + (0.0051*BIRC5). Risk score served as the independent prognostic factor as per the multivariate analysis. TCGA, THPA, and data from the Guangxi Medical University Cancer Hospital were used to confirm the predictive validity of risk scores for the prognosis of HCC patients. Conclusion: This study offers molecular insights regarding the involvement of autophagy in HCC patients, along with a probable prognostic signature for determining the outcome (prognosis) of HCC patients.

Immunotherapy combination with regorafenib for refractory hepatocellular carcinoma: A real-world study.

PURPOSE: To compare the efficacy and safety of immunotherapy plus regorafenib versus regorafenib only in patients with pretreated hepatocellular carcinoma (HCC). METHODS: Immunotherapy plus regorafenib or regorafenib alone was analyzed in patients with advanced HCC with documented tumor progression on front-line therapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs) were assessed. RESULTS: Of the 125 patients enrolled in this study, 50 patients received combination (pCOM) treatment as front-line treatment, and 60 patients received monotherapy (pMONO) as front-line treatment. In the pCOM cohort, median OS was significantly longer with for patients regorafenib plus immunotherapy than regorafenib alone treatment (15.0 vs. 2.0 months; P = 0.035). The DCR numerically increased in the regorafenib plus immunotherapy treatment in both cohorts (40.6 % vs. 22.2 %, 72.7 % vs. 54.7 %, respectively). There were no differences in PFS with regorafenib according to whether or not regorafenib was combined with immunotherapy in the pCOM and pMONO cohorts (PFS, P = 0.17, P = 0.91, respectively). Regarding the number of TRAEs occurred, regorafenib plus immunotherapy group was comparable to regorafenib group in the pCOM cohort (65.6 % vs. 72.2 %). In the pMONO cohort, TRAEs occurred in fewer patients receiving regorafenib than regorafenib plus immunotherapy (69.8 % vs. 95.5 %). CONCLUSIONS: Immunotherapy plus regorafenib may significantly improve clinical outcomes and have a manageable safety profile compared with regorafenib monotherapy in advanced HCC after front-line therapy failure. The efficacy of combination therapy needs to be validated in prospective studies with large samples.

Long-term effects of total vs. partial pancreatectomy among patients with pancreatic cancer: a population-based study.

Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations. Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis. Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05). Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma.

In this study, we aim to identify the clinical significance of basonuclin 1 (BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI: -3.649 to -1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445-0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low-BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 (FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

The roles of the cell division cycle-associated gene family in hepatocellular carcinoma.

BACKGROUND: The members of the cell division cycle-associated (CDCA) gene family are significant regulators of cell proliferation known to play key roles in various cancers. However, the function of CDCA genes in hepatocellular carcinoma (HCC) is unclear. The aim of this research was to clarify the roles of CDCA family members in HCC using bioinformatics analysis tools. METHODS: We studied data on the mRNA and protein expression of CDCA genes and survival in patients with HCC using the Oncomine, UALCAN, HPA, CCLE, LinkedOmics, cBioPortal, and Metascape databases. RESULTS: Significant overexpression of all CDCA members was found in HCC tissues. The expression levels of CDCAs were related to the tumor stage, and high expression levels were correlated with a low survival rate in patients with HCC. Also, we observed a high mutation rate (45%) of CDCAs in the HCC samples, which manifested as deep deletion, amplification, or increased mRNA expression. In the correlation analysis, we found that any 2 CDCA members were significantly positively correlated with each other. Cycle-related genes including AHCTF1, AKT1, BIRC5, CENPF, CENPL, and CENPQ were closely associated with CDCA gene alterations. CONCLUSIONS: The findings of this study indicate that CDCAs may be potential therapeutic targets and prognostic indicators for patients with HCC.

A novel prognostic nomogram for hepatocellular carcinoma after thermal ablation.

It remains impossible to accurately assess the prognosis after thermal ablation in patients with hepatocellular carcinoma (HCC). Our aim was to build a nomogram to predict the survival rate of HCC patients after thermal ablation. We developed and validated a nomogram using data of 959 HCC patients after thermal ablation from two centers. Harrell's concordance index (C-index), calibration plot and Decision curve analysis (DCA) were used to measure the performance of the nomogram, and we compared it with the Barcelona Clinic Liver Cancer (BCLC) staging system and a previous nomogram. Six variables including age, serum albumin, operation method, risk area, tumor number and early recurrence were selected to construct the nomogram. In the training cohort, internal validation cohort, and external validation cohort, the nomogram all had a higher C-index to predict survival rate than both the BCLC staging system and the previous nomogram (0.736, 0.558 and 0.698, respectively; 0.763, 0.621 and 0.740, respectively; and 0.825, 0.551 and 0.737, respectively). Calibration plots showed a high degree of consistency between prediction and actual observation. Decision curve analysis (DCA) presented that compared with BCLC system and the previous nomogram, our nomogram had the highest net benefit. In all three cohorts, the nomogram could accurately divide patients into three subgroups according to predicted survival risk. A nomogram was developed and validated to predict survival of HCC patients who underwent thermal ablation, which is helpful for prognostic prediction and individual surveillance in clinical practice.

Application of iron/barium ferrite/carbon-coated iron nanocrystal composites in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) has been widely used in clinical practice as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the current therapeuticeffect of TACE is far from satisfactory and thus requires further improvement. TACE combined with multifunctional magnetic particles may be a promising approach for the treatment of HCC. In this study, we designed a new magnetic drug carrier system consisting of micron-sized iron powder, barium ferrite (BaFe12O19), and carbon-coated iron nanocrystals (CCINs). CCINs possess properties, such as high drug loading and sustained release. BaFe12O19 could attract both CCINs and iron powder to form larger clusters after magnetization. Altogether, the triple therapeutic effects of chemotherapeutic enhancement, embolization, and thermal ablation could be realized herein. Further experiments indicate that the system has a high drug-loading capacity, good controlled-release effect, and no significant cytotoxicity. Under the action of a medium-frequency magnetic induction device, the magnetic induction temperature could reach 43 °C in one min while the maximum temperature of 70.8 °C could be reached in 2.5 h. Overall, this new carrier system displayed excellent antitumor effects in a mouse model. Our findings demonstrate the great application prospects of this system in TACE for HCC.

A novel three-dimensional heterojunction photocatalyst for the photocatalytic oxidation of crystal violet and reduction of Cr6.

A novel 3-D heterojunction photocatalyst Ag2CO3/BiVO4 was successfully fabricated. It exhibits excellent photocatalytic performances for the photocatalytic oxidation of crystal violet and reduction of Cr6+, which is ascribed to the suppression of charge recombination, and increasing lifetime of the charge carriers confirmed by the result of time-resolved fluorescence emission decay spectra and photoelectrochemical measures. The electron spin resonance result also suggests that heterojunction structure can improve separation efficiency of photogenerated carriers and favor to form •OH radicals. Moreover, ten intermediates and products for the photocatalytic oxidation degradation of crystal violet are identified by GC-MS.