m6A demethylation of FOSL1 mRNA protects hepatoma cells against necrosis under glucose deprivation.

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.

Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in Sepsis.

This research utilized single-cell RNA sequencing to map the immune cell landscape in sepsis, revealing 28 distinct cell clusters and categorizing them into nine major types. Delving into the monocyte/macrophage subclusters, 12 unique subclusters are identified and pathway enrichment analyses are conducted using KEGG and GO, discovering enriched pathways such as oxidative phosphorylation and antigen processing. Further GSVA and AUCell assessments show varied activation of interferon pathways, especially in subclusters 4 and 11. The clinical correlation analysis reveals genes significantly linked to survival outcomes. Additionally, cellular differentiation in these subclusters is explored. Building on these insights, the differential gene expression within these subclusters is specifically scrutinized, which reveal MYOF as a key gene with elevated expression levels in the survivor group. This finding is further supported by in-depth pathway enrichment analysis and the examination of cellular differentiation trajectories, where MYOF's role became evident in the context of immune response regulation and sepsis progression. Validating the role of the MYOF gene in sepsis, a dose-dependent response to LPS in THP-1 cells and C57 mice is observed. Finally, inter-cellular communications are analyzed, particularly focusing on the MYOF+Mono/Macro subcluster, which indicates a pivotal role in immune regulation and potential therapeutic targeting.

Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.

Background and aims: Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. Methods: This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. Results: High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Conclusion: Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.

Integrative analysis reveals that SLC38A1 promotes hepatocellular carcinoma development via PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism.

Although hepatocellular carcinoma (HCC) is rather frequent, little is known about the molecular pathways underlying its development, progression, and prognosis. In the current study, we comprehensively analyzed the deferentially expressed metabolism-related genes (MRGs) in HCC based on TCGA datasets attempting to discover the potentially prognostic genes in HCC. The up-regulated MRGs were further subjected to analyze their prognostic values and protein expressions. Twenty-seven genes were identified because their high expressions were significant in OS, PFS, DFS, DSS, and HCC tumor samples. They were then used for GO, KEGG, methylation, genetics changes, immune infiltration analyses. Moreover, we established a prognostic model in HCC using univariate assays and LASSO regression based on these MRGs. Additionally, we also found that SLC38A1, an amino acid metabolism closely related transporter, was a potential prognostic gene in HCC, and its function in HCC was further studied using experiments. We found that the knockdown of SLC38A1 notably suppressed the growth and migration of HCC cells. Further studies revealed that SLC38A1 modulated the development of HCC cells by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism. In conclusion, this study identified the potentially prognostic MRGs in HCC and uncovered that SLC38A1 regulated HCC development and progression by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism, which might provide a novel marker and potential therapeutic target in HCC.

FBXO43 increases CCND1 stability to promote hepatocellular carcinoma cell proliferation and migration.

Background and Aims: Abnormal expression of E3 ubiquitin ligase plays an important role in the development and progression of hepatocellular carcinoma (HCC), although the mechanism has remained elusive. This study aimed to investigate the biological function and potential mechanism of FBXO43 in HCC. Methods: FBXO43 expression in tissues and cells were detected by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method and Cox regression analysis were used to explore the correlation between the expression level of FBXO43 and the clinical survival. MTT assay, EdU incorporation, colony formation, Transwell, and wound healing assays were performed to evaluate the function of FBXO43 in cell proliferation and migration in vitro. The interaction between FBXO43 and cyclin D1 (CCND1) was assessed by co-immunoprecipitation (Co-IP) assay and in vivo ubiquitination assay. Results: We found that FBXO43 was upregulated in HCC patient tissues and positively associated with poor clinicopathological features. Meanwhile, HCC patients with high expression of FBXO43 had shorter overall survival (OS) and disease-free survival (DFS). Furthermore, knockdown of FBXO43 inhibited HCC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in HCC cells. Mechanistically, FBXO43 interacted with CCND1 and promoted its stability by polyubiquitination, leading to HCC cell proliferation, migration and EMT. Functional rescue experiments demonstrated that knockdown of CCND1 blocks FBXO43-mediated cell proliferation and metastasis. Conclusions: FBXO43, as an independent prognostic biomarker, promotes HCC cell proliferation, metastasis and EMT by stability of CCND1, which provides a new potential strategy for HCC treatment by targeting FBXO43-CCND1 axis.

Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstruction.

Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.

The relationship between the use of metformin and the risk of pancreatic cancer in patients with diabetes: a systematic review and meta-analysis.

OBJECTIVE: We aim to evaluate the relationship between the use of metformin and the risk of pancreatic cancer in type 2 diabetes patients. METHOD: We systematically searched the observational studies on PubMed, Embase, Web of Science, Cochrane Library, clinicalrials.gov, and CNKI databases, extracted relevant data, combined the OR value and 95% CI using the random effect model, and conducted a sensitivity analysis, subgroup analysis, and meta-regression to evaluate the size and stability of this relationship. RESULT: Twenty-nine studies from twenty-four articles met our inclusion criteria, including more than 2 million subjects. Overall analysis showed that compared with no use of metformin, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.82, 95% CI (0.69, 0.98)). Subgroup analysis showed that compared with the use of hypoglycemic drugs, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.79, 95% CI (0.66, 0.94)). However, compared with no drugs or only diet therapy, metformin users might increase the risk of pancreatic cancer (OR = 2.19, 95% CI (1.08, 4.44)). Sensitivity analysis confirmed the stability of the study, and there was no significant publication bias. CONCLUSION: Compared with the no-use of metformin, metformin users with diabetes can reduce the risk of pancreatic cancer. More research is needed to prove it works.

FNBP4 is a Potential Biomarker Associated with Cuproptosis and Promotes Tumor Progression in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that lacks an efficient therapeutic approach because of its elusive molecular mechanisms. This study aimed to investigate the biological function and potential mechanism of formin-binding protein 4 (FNBP4) in HCC. Methods: FNBP4 expression in tissues and cells were detected by quantitative real-time PCR (qRT‒PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method was used to explore the correlation between the FNBP4 expression and clinical survival. MTT, EdU incorporation, colony formation, and Transwell assays were performed to evaluate the function of FNBP4 in cell proliferation and migration in vitro. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the potential mechanism of FNBP4. The prognostic risk signature and nomogram were constructed to demonstrate the prognostic value of FNBP4. Results: We found that FNBP4 was upregulated in patients with HCC and associated with poor overall survival (OS). Furthermore, knockdown of FNBP4 inhibited the proliferation and migration in HCC cells. Then, we performed a KEGG pathway analysis of the coexpressed genes associated with FNBP4 and found that FNBP4 may be associated with tumor-related signaling pathways and cuproptosis. We verified that FNBP4 could cause cell cycle progression and inactivation of the hippo signaling pathway. A prognostic risk signature containing three FNBP4-related differentially expressed cuproptosis regulators (DECRs) was established and can be used as an independent risk factor to evaluate the prognosis of patients with HCC. In addition, a nomogram including a risk score and clinicopathological factors was used to predict patient survival probabilities. Conclusion: FNBP4, as a potential biomarker associated with cuproptosis, promotes HCC cell proliferation and metastasis. We provide a new potential strategy for HCC treatment by targeting FNBP4.

Geometrical analysis identified morphological features of hydrogel-induced cancer stem cells in synovial sarcoma model cells.

Cancer stem cells (CSCs) has been a key target to cure cancer patients completely. Although many CSC markers have been identified, they are frequently cancer type-specific and those expressions are occasionally variable, which becomes an obstacle to elucidate the characteristics of the CSCs. Here we scrutinized the relationship between stemness elevation and geometrical features of single cells. The PAMPS hydrogel was utilized to create the CSCs from mouse myoblast C2C12 and its synovial sarcoma model cells. qRT-PCR analysis confirmed the significant increase in expression levels of Sox2, Nanog, and Oct3/4 on the PAMPS gel, which was higher in the synovial sarcoma model cells. Of note, the morphological heterogeneity was appeared on the PAMPS gel, mainly including flat spreading, elongated spindle, and small round cells, and the Sox2 expression was highest in the small round cells. To examine the role of morphological differences in the elevation of stemness, over 6,400 cells were segmented along with the Sox2 intensity, and 12 geometrical features were extracted at single cell level. A nonlinear mapping of the geometrical features by using uniform manifold approximation and projection (UMAP) clearly revealed the existence of relationship between morphological differences and the stemness elevation, especially for C2C12 and its synovial sarcoma model on the PAMPS gel in which the small round cells possess relatively high Sox2 expression on the PAMPS gel, which supports the strong relationship between morphological changes and the stemness elevation. Taken together, these geometrical features can be useful for morphological profiling of CSCs to classify and distinguish them for understanding of their role in disease progression and drug discovery.

Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend  = .021) in a linear dose-response manner (Pnonlinearity  = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction  = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells.

Retinoic acid (RA) and its synthetic derivatives, retinoids, have been established as promising anticancer agents based on their ability to regulate cell proliferation and survival. Clinical trials, however, have revealed that cancer cells often acquire resistance to retinoid therapy. Therefore, elucidation of underlying mechanisms of retinoid resistance has been considered key to developing more effective use of retinoids in cancer treatment. In this study, we show that constitutive activation of ERK MAP kinase signaling, which is often caused by oncogenic mutations in RAS or RAF genes, suppresses RA receptor (RAR) signaling in breast cancer cells. We show that activation of the ERK pathway suppresses, whereas its inhibition promotes, RA-induced transcriptional activation of RAR and the resultant upregulation of RAR-target genes in breast cancer cells. Importantly, ERK inhibition potentiates the tumor-suppressive activity of RA in breast cancer cells. Moreover, we also reveal that suppression of RAR signaling and activation of ERK signaling are associated with poor prognoses in breast cancer patients and represent hallmarks of specific subtypes of breast cancers, such as basal-like, HER2-enriched and luminal B. These results indicate that ERK-dependent suppression of RAR activity underlies retinoid resistance and is associated with cancer subtypes and patient prognosis in breast cancers.

miR-550a-5p promotes the proliferation and migration of hepatocellular carcinoma by targeting GNE via the Wnt/ß-catenin signaling pathway.

Liver cancer is one of the most common tumors with a high malignant degree in the world. Its diagnosis and treatment are very difficult and limited. More novel and powerful DAT strategies are urgently needed to break this situation. An increasing number of studies have shown that microRNAs (miRNAs) could be used not only as biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) but also as important targets for molecular targeted therapy. However, the role of miR-550a-5p in HCC and its specific mechanism remain unclear. Here we proposed and verified the hypothesis that the miR-550a-5p could regulate the progression of HCC and was positively associated with poor prognosis. We found that decreased miR-550a-5p would inhibit the proliferation and migration of HCC cell lines (HCs) by performing relevant assays. Interestingly, knocking down GNE could reverse the above effect of miR-550a-5p on HCs. Meanwhile, the western blot results showed that the Wnt/ß-catenin signaling pathway was at least partly involved in the regulation of HCC by miR-550a-5p. In addition, we also found that miR-550a-5p could suppress the growth of HCC in vivo via a xenograft tumor model assay. All in all, we draw a conclusion that the miR-550a-5p/GNE axis functioned as an important role in promoting the progression of HCC via the Wnt/ß-catenin signaling pathway.

Fried food consumption and the risk of pancreatic cancer: A large prospective multicenter study.

Background and aims: Whether fried food consumption is associated with the risk of pancreatic cancer remains elusive. We aimed to examine this association in a US population. Methods: A population-based cohort of 101,729 US adults was identified. Fried food consumption was assessed with a validated food frequency questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Explanatory analyses were conducted to identify main contributor(s) to the observed association. Results: During an average follow-up of 8.86 years (900871.2 person-years), 402 pancreatic cancer cases occurred. High consumption of total fried foods (deep-fried plus pan-fried foods; HRquartile4 vs. 1 0.71, 95% CI 0.51-0.99, P trend = 0.047) and deep-fried foods (HRquartile 4 vs. 1 0.64, 95% CI 0.47-0.88, P trend = 0.011), but not pan-fried foods (HRquartile 4 vs. 1 0.98, 95% CI 0.73-1.32; P trend = 0.815), was found to be associated with a reduced risk of pancreatic cancer in a non-linear dose-response manner, which was not modified by predefined stratification factors and persisted in sensitivity analyses. In explanatory analyses, only chip consumption was found to be inversely associated with the risk of pancreatic cancer; consistently, the initial significant associations between total fried food and deep-fried food consumption and the risk of pancreatic cancer changed to be non-significant after omitting or further adjusting for chip consumption. Conclusion: Consumption of deep-fried foods, but not pan-fried foods, is inversely associated with the risk of pancreatic cancer in this US population. The role of deep-fried foods in reducing the risk of pancreatic cancer appears to be mainly attributable to chips. More studies are needed to confirm our findings in other populations and settings.

Transcatheter Arterial Chemoembolization in Combination With High-Intensity Focused Ultrasound for Intermediate and Advanced Hepatocellular Carcinoma: A Meta-Analysis.

Background: The study was conducted to explore whether high-intensity focused ultrasound (HIFU) can improve the effect of transcatheter arterial chemoembolization (TACE) in intermediate and advanced hepatocellular carcinoma (HCC). Methods: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CQVIP, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) comparing the effect of TACE in combination with HIFU group (group A) to TACE alone group (group B) in treating intermediate and advanced HCC. The primary outcomes were overall survival (OS) rate and tumor response rate. The odds ratio (OR) and 95% confidence interval (CI) for each study were calculated and then pooled with fixed effects model or random effects model. Sensitivity analyses and subgroup analyses were conducted. A publication bias was also evaluated. Results: After literature selection, eleven RCTs involving 803 patients were included in this meta-analysis. This meta-analysis revealed that group A was associated with an increased 6-month OS rate (OR = 0.20), 12-month OS rate (OR = 0.23), 24-month OS rate (OR = 0.32), and overall response rate (WHO criterion, OR = 0.22; RECIST criterion, OR = 0.30). Furthermore, subgroup analyses showed no bias in the result. Given the limited number of studies that reported major complications, no additional meta-analysis of complication was conducted. Despite no special treatment, any complication following HIFU treatment was found to subside within 3-7 days. Conclusion: TACE in combination with HIFU is associated with increased OS and tumor response in intermediate and advanced HCC. Current evidence supports the use of HIFU after TACE treatment in intermediate and advanced HCC.

eIF3a-PPP2R5A-mediated ATM/ATR dephosphorylation is essential for irinotecan-induced DNA damage response.

OBJECTIVES: The individual differences and pervasive resistance seriously hinder the optimization of irinotecan-based therapeutic effectiveness. Eukaryotic translation initiation factor 3a (eIF3a) plays a key role in tumour occurrence, prognosis and therapeutic response. This study focused on the role of eIF3a in irinotecan-induced DNA damage response. MATERIALS AND METHODS: The cck8 cell viability and clone survival analyses were used to test the regulatory role of eIF3a on irinotecan sensitivity in HT29 and CACO2 cell lines in vitro. This regulatory role was also verified in vivo by conducting subcutaneous xenograft model. Irinotecan-induced DNA damage, cell cycle arrest and apoptosis were tested by flow cytometry analysis, TUNEL staining, western blot and comet assays. The immunofluorescence, co-IP, luciferase reporter assay, RIP and flow cytometric analyses were carried out to investigate the underline mechanism. RESULTS: We demonstrated that eIF3a continuously activates ATM/ATR signal by translationally inhibiting PPP2R5A, a phosphatase that directly dephosphorylates and inactivates ATM/ATR after DNA repair complete. Suppression of PPP2R5A resulted in chronic ATM/ATR phosphorylation and activation, impairing DNA repair and enhancing irinotecan sensitivity. CONCLUSIONS: Our study suggested eIF3a with a high potential to influence phenotypic functions, which may contribute substantially to the early identification of susceptible individuals and the provision of personalized medication to irinotecan-treated patients.

Hydroxyapatite-hybridized double-network hydrogel surface enhances differentiation of bone marrow-derived mesenchymal stem cells to osteogenic cells.

Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF-ß1, BMP-2, Runx2, Col-1, ALP, OPN, BSP, and OCN) in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for Runx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker-positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.

Type 2 diabetes prevention diet and the risk of pancreatic cancer: A large prospective multicenter study.

BACKGROUND & AIMS: Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. METHODS: A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. RESULTS: After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4versus1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend = 0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4versus1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4versus1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction = 0.095). CONCLUSIONS: Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.

Contrast enhanced ultrasound in diagnosing liver lesion that spontaneously disappeared: A case report.

BACKGROUND: Focal liver lesions (FLLs) are abnormal masses that are distinguishable from the surrounding liver parenchyma, solid or cystic and may be benign or malignant. They are usually detected incidentally on abdominal examinations. The classification of FLLs is very important as it directly determines the diagnosis and treatment of patients. CASE SUMMARY: A 46-year-old male patient was admitted into the hospital with tarry stool, during the investigation of this issue an incidental FLL was detected. Upon further investigation of this "incidentaloma" computerized tomography and magnetic resonance imaging reached contradictory conclusions. The lesion was then further investigated using contrast-enhanced ultrasound (CEUS) with an initial diagnosis of idiopathic FLL was acquired and observation of the FLL over time need for final diagnosis, however in the follow up the FLL disappeared spontaneously. CONCLUSION: CEUSs value for characterization of FLLs is undeniable, especially when other methods produce inconsistent results, is undeniable but with its limitations. Why and how the FLL disappeared is not known, and can be only hypothesized it was a pseudolesion.

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model.

BACKGROUND: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. HYPOTHESIS: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. RESULTS: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. CONCLUSION: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. CLINICAL RELEVANCE: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective Study of 101,695 American Adults.

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.