APOA1 mRNA and serum APOA1 protein as diagnostic and prognostic biomarkers in gastric cancer.

Background: Gastric cancer (GC) remains a formidable challenge in oncology, ranking as a leading cause of cancer mortality globally. This underscores an urgent need for innovative prognostic markers that can revolutionize patient management and outcomes. Recent insights into cancer biology have spotlighted the profound influence of lipid metabolism alterations on tumorigenesis, tumor progression, and the tumor microenvironment. These alterations not only fuel cancer cell growth and proliferation but also play a strategic role in evading immune surveillance and promoting metastasis. The intricate web of lipid metabolism in cancer cells, characterized by deregulated uptake, synthesis, and oxidation of fatty acids (FAs), opens new avenues for targeted therapeutic interventions and prognostic evaluations. Specifically, this study zeroes in on apolipoprotein A-I (APOA1), a key player in lipid metabolism, to unearth its prognostic value in GC. By delving into the role of lipid metabolism-related genes, particularly APOA1, we aim to unveil their potential as groundbreaking biomarkers for GC prognosis. This endeavor not only aims to enhance our understanding of the molecular underpinnings of GC but also to spearhead the development of lipid metabolism-based strategies for improved diagnostic, prognostic, and therapeutic outcomes. Methods: Transcriptomic and clinical data from GC patients and healthy individuals were sourced from The Cancer Genome Atlas (TCGA) database, a comprehensive project that molecularly characterizes over 20,000 primary cancer and matched normal samples across 33 cancer types. Significantly differentially expressed lipid metabolism-related genes were identified using the "limma" package in R. Prognostic genes were selected via univariate Cox regression analysis. Differential gene enrichment analysis was performed using Metascape (http://www.metascape.org). The Human Protein Atlas (HPA, https://www.proteinatlas.org) provided information on APOA1 protein expression in GC and healthy tissues. Immune cell infiltration was analyzed using the CIBERSORT algorithm (http://cibersort.stanford.edu). Results: Significant differences in lipid metabolism-related gene expression were observed between GC and normal tissues, closely linked to FA metabolism, oxidoreductase activity, and sphingolipid metabolism. APOA1 emerged as a potential prognostic biomarker by intersecting prognostic and differentially expressed lipid metabolism genes. Immunohistochemical analysis confirmed APOA1 downregulation in GC. The receiver operating characteristic (ROC) analysis demonstrated its predictive value, with the area under the curve (AUC) being 0.64 [95% confidence interval (CI): 0.52-0.76]. APOA1 expression correlated with immune cell infiltrations. Clinical serum APOA1 results revealed lower levels in GC patients (1.38 vs. 1.26; P<0.05), associated with poor prognosis (hazard ratio =1.50; P<0.001) and clinical characteristics. ROC analysis of serum APOA1 demonstrated good diagnostic ability (AUC: 0.63, 95% CI: 0.61-0.65). Serum APOA1 levels significantly increased after treatment. Conclusions: This study highlights lipid metabolism reprogramming in GC and identifies APOA1 as a potential diagnostic and prognostic biomarker, suggesting its clinical utility in managing GC.

Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer.

BACKGROUND: Parthanatos is a novel programmatic form of cell death based on DNA damage and PARP-1 dependency. Nevertheless, its specific role in the context of gastric cancer (GC) remains uncertain. METHODS: In this study, we integrated multi-omics algorithms to investigate the molecular characteristics of parthanatos in GC. A series of bioinformatics algorithms were utilized to explore clinical heterogeneity of GC and further predict the clinical outcomes. RESULTS: Firstly, we conducted a comprehensive analysis of the omics features of parthanatos in various human tumors, including genomic mutations, transcriptome expression, and prognostic relevance. We successfully identified 7 cell types within the GC microenvironment: myeloid cell, epithelial cell, T cell, stromal cell, proliferative cell, B cell, and NK cell. When compared to adjacent non-tumor tissues, single-cell sequencing results from GC tissues revealed elevated scores for the parthanatos pathway across multiple cell types. Spatial transcriptomics, for the first time, unveiled the spatial distribution characteristics of parthanatos signaling. GC patients with different parthanatos signals often exhibited distinct immune microenvironment and metabolic reprogramming features, leading to different clinical outcomes. The integration of parthanatos signaling and clinical indicators enabled the creation of novel survival curves that accurately assess patients' survival times and statuses. CONCLUSIONS: In this study, the molecular characteristics of parthanatos' unicellular and spatial transcriptomics in GC were revealed for the first time. Our model based on parthanatos signals can be used to distinguish individual heterogeneity and predict clinical outcomes in patients with GC.

Post-endoscopic submucosal dissection phlegmonous enteritis: A case report and literature review.

Background: This study presents the initial case of phlegmonous enteritis following endoscopic submucosal dissection (ESD), a rare and potentially fatal complication. Additionally, a comprehensive review of relevant literature is provided. Case report: A 66-year-old female patient, diagnosed with Hashimoto's thyroiditis and thrombocytopenia, underwent ESD to address a laterally spreading tumor located in the ascending colon. After the procedure, the patient manifested abdominal pain and a high fever, was diagnosed with peritonitis, necessitating an emergency exploratory laparotomy and right hemicolectomy. Subsequent histological examination indicated a significant presence of neutrophil infiltration across all layers of the intestines. The ascites culture yielded the growth of Escherichia coli. Literature review: A search was conducted in the PubMed database to identify case reports conforming to the definition of phlegmonous enteritis proposed by Rokitansky et al. We retrieved about 30 studies regarding phlegmonous enteritis from 1951 to 2022, with around 39 cases. Among these, only 28 patients had comprehensive medical data available. Subsequently, an examination of the literature was undertaken to explore the pathogenesis, prevention, and treatment of phlegmonous enteritis. Conclusion: The possibility of phlegmonous enteritis should be taken into consideration in cases of unexplained acute abdomen, particularly in patients with compromised immunity, in order to provide active surgical and antibiotic interventions.

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Design and Verification of Deep Submergence Rescue Vehicle Motion Control System.

A six degree-of-freedom (DOF) motion control system for docking with a deep submergence rescue vehicle (DSRV) test platform was the focus of this study. The existing control methods can meet the general requirements of underwater operations, but the complex structures or multiple parameters of some methods have prevented them from widespread use. The majority of the existing methods assume the heeling effect to be negligible and ignore it, achieving motion control in only four or five DOFs. In view of the demanding requirements regarding positions and inclinations in six DOFs during the docking process, the software and hardware architectures of the DSRV platform were constructed, and then sparse filtering technology was introduced for data smoothing. Based on the adaptive control strategy and with a consideration of residual static loads, an improved S-plane control method was developed. By converting the force (moment) calculated by the controller to the body coordinate system, the complexity of thrust allocation was effectively reduced, and the challenge of thrust allocation in the case of a high inclination during dynamic positioning was solved accordingly. The automatic control of the trimming angle and heeling angle was realized with the linkage system of the ballast tank and pump valve. A PID method based on an intelligent integral was proposed, which not only dealt with the integral "saturation" problem, but also reduced the steady-state error and overshooting. Water pool experiments and sea trials were carried out in the presence of water currents for six-DOF motion control. The responsiveness and precision of the control system were verified by the pool experiment and sea trial results and could meet the control requirements in engineering practice. The reliability and operational stability of the proposed control system were also verified in a long-distance cruise.

SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions.

Chronic hepatitis B virus (HBV) infection remains a significant public health concern worldwide. Several metabolic processes regulate HBV DNA replication, including autophagy and lipid metabolism. In this study, we clarified the effect of lipids on HBV replication and elucidated possible mechanisms. We discovered that lipid metabolic gene expression levels were negatively correlated with the HBV DNA in plasma. Our data showed that fatty acid stimulation significantly reduced HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) levels in HepG2.2.15 cells, which are human hepatoma cell cultures transfected with HBV DNA. The Stearoyl coenzyme A desaturase 1 (SCD1)-autophagy pathway has also been implicated in inhibiting HBV replication by fatty acids stimulation. SCD1 knockdown deregulates the inhibitory effect of fatty acids on HBV by enhancing autophagy. When 3 methyladenine (3MA) was added, the inhibitory effects of specific autophagy inhibitors eliminated the positive effects of SCD1 knockdown on HBV replication. Our results indicate that SCD1 participates in the regulation of inhibition of HBV replication by fatty acids stimulation through regulating autophagy.

WKYMVm Works by Targeting Immune Cells.

WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met) is a synthetic hexapeptide identified as a potent agonist of FPRs. FPRs are widely expressed on the cell membrane of immune cells. Therefore, WKYMVm participates in the regulation of immune cells by activating FPRs, and plays a therapeutic role in infections, tumors, autoimmune diseases and so on. WKYMVm can promote the chemotactic migration, increase the bactericidal activity of neutrophils and monocytes. WKYMVm also regulates the number and polarization of macrophages, affects the maturation of DCs and the differentiation of T cells, and promotes the activation and chemotaxis of NK cells. These functions make WKYMVm a candidate drug for immunotherapy. In this paper, we summarize the regulatory effects and underlying mechanisms of WKYMVm on six immune cells (neutrophils, monocytes, macrophages, DCs, T cells and NK cells) to increase comprehensive understanding and promote further research on WKYMVm.

Effect of Layered Double Hydroxides on the Deterioration Process of Cement Paste under Sulfate Attack.

This study investigated the effect of layered double hydroxides (LDHs) on the deterioration process of cement paste in the sulfate environment. Cement pastes with the addition of original and calcined LDHs at 2.5 wt.% and 5.0 wt.% of cement were exposed to Na2SO4 solution for 360 days. The macroscopic performance of the cement paste was assessed based on mass variation, porosity, compressive strength, and content of sulfate ions. Furthermore, the microhardness, microstructures, and composition of the degraded pastes were examined using Vickers hardness (HV), mercury intrusion porosimetry (MIP), scanning electron microscope (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results indicate that cement paste incorporated with LDHs can mitigate the corrosion caused by sulfate effectively, especially in the case of calcined LDHs (C-LDHs), which primarily increase the adsorption of sulfate. Compared with the control specimen, the 180 d compressive strength loss ratio of specimens with 2.5 wt.% and 5.0 wt.% of C-LDHs decreased by 63.66% and 80.51%, respectively. Moreover, LDHs can reduce the amount of ettringite crystals, densify the microstructure, and refine the pore structure to mitigate the cement paste's sulfate corrosion significantly. Compared with the control specimen, the 180 d harmful pore volume fraction of specimens laced with 2.5 wt.% and 5.0 wt.% C-LDHs decreased by 43.77% and 54.51%, respectively. In terms of the content of C-LDHs, an optimal content of C-LDHs could ensure the dominant effect of adsorption, while excessive C-LDHs could refine pores. In addition, Vickers hardness has an excellent correlation with compressive strength, which could precisely predict the compressive strength. Moreover, by combining the Vickers hardness distribution and content distribution of sulfate ions, the cross-section of the paste could be classified into four regions to evaluate the deterioration process accurately: the degraded zone, the strengthened zone, the invaded zone, and the intact zone.

Evaluation of Pozzolanic and Alkali-Activated Reactivity of Low-Purity Calcium Bentonite.

Alkali-activated cement (AAC) is a sustainable building material with low carbon emissions, but it has a growing demand for raw materials. In this study, the potential of low-purity modified calcium bentonite (CB) as a raw material for AAC was evaluated. The thermodynamic changes and pozzolanic properties of calcined CB were determined using X-ray diffraction (XRD), thermogravimetry-differential thermal analysis (TG-DTA), zeta potential, and a strength activity index (SAI) test. The compressive strength test, scanning electron microscopy-energy dispersive spectrometer (SEM-EDS), and Fourier-transform infrared (FTIR) spectroscopy were performed to examine the compatibility between CB and AAC. It was revealed that CB is a low-purity clay with low-pozzolanic activity. Calcination enhanced its pozzolanic activity, and the optimum temperature is 750 °C. The incorporation of modified CB improved the mechanical properties of AAC, and low-temperature modified CB had better compatibility with AAC than the high-temperature modified CB. Calcination at 150 °C had little effect on the structure of CB, and the water absorption of montmorillonite increased the ion concentration, increasing the rate and degree of hydration. Furthermore, low-temperature calcination had a dissolution-precipitation effect, resulting in leaf-like CaO·SiO2·H2O (C-S-H) gels, whereas the high-temperature calcination of CB was very reactive, resulting in flower-like C(N)-S-H gels.

Diagnostic accuracy of linked colour imaging versus white light imaging for early gastric cancers: a prospective, multicentre, randomized controlled trial study.

BACKGROUND: Linked colour imaging (LCI) is a novel new image-enhanced endoscopy (IEE) technology that produces bright and vivid images. The aim of this study was to assess the ability of LCI to improve the diagnostic accuracy of early gastric cancer (EGC) relative to white light imaging (WLI). MATERIALS AND METHODS: We performed this study on patients undergoing screening endoscopy from 12 medical institutions in China. Patients were randomly assigned to receive WLI followed by LCI or LCI followed by WLI. The primary outcome was to compared the diagnostic accuracy between LCI and WLI for EGC/high-grade intraepithelial neoplasms. Secondary outcomes included the numbers of suspicious lesions, neoplastic lesions and examination time by using LCI detected versus using WLI. RESULTS: A total of 1924 patients were randomly selected, and 1828 were included in the analysis. The diagnostic accuracy for EGC, which was 78.8% by using LCI and 68.4% by using WLI (p < .0001). More suspicious lesions were detected by LCI than by WLI (n = 1235 vs. 1036, p = .031), especially among differentiated EGC (p = .013). LCI greatly shortened the examination time compared with WLI (p = .019). CONCLUSIONS: LCI has better accuracy and shorter examination time in diagnosing EGC than WLI (Clinical trial registration: NCT03092414).Key messagesCompared with white light imaging (WLI), the diagnostic accuracy, sensitivity and specificity increased by using LCI.More lesions were detected by LCI alone than by WLI alone, especially among differentiated EGC.LCI may be used as a screening tool for routine clinical observation.

Magnetically Controlled Capsule Endoscopy for Assessment of Antiplatelet Therapy-Induced Gastrointestinal Injury.

BACKGROUND: Gastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon. OBJECTIVES: The authors sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury by means of a novel magnetically controlled capsule endoscopy system in patients at low bleeding risk. METHODS: Patients (n = 505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n = 168), clopidogrel plus placebo (n = 169), or aspirin plus clopidogrel (n = 168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy. RESULTS: Gastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) than with DAPT (94.3% vs 99.2%; P = 0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs 95.2%; P = 0.006), including fewer new ulcers (8.5% vs 38.1%; P = 0.009). Clinical gastrointestinal bleeding from 6 to 12 months was less with SAPT than with DAPT (0.6% vs 5.4%; P = 0.001). CONCLUSIONS: Despite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel from 6 to 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months. (OPT-PEACE [Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by Ankon Magnetically Controlled Capsule Endoscopy]; NCT03198741).

Snare-assisted precutting and dual-knife fistulotomy performed during difficult biliary cannulation in a patient with an ectopic papilla of Vater.

Endoscopic retrograde cholangiopancreatography is widely used in the diagnosis and treatment of pancreatobiliary diseases; however, successful biliary cannulation is a prerequisite for this operation. We herein present a new method in a patient in whom cannulation was difficult. A 56-year-old man was admitted to the hospital with choledocholithiasis. Endoscopic retrograde cholangiopancreatography was performed, and duodenoscopy revealed that the patient's duodenal papilla was located at the initial part of the horizontal segment of the duodenum. Because of the ectopic location of the duodenal papilla, the guidewire could not be inserted into the biliary and pancreatic duct. Therefore, we performed a new method to resolve the problem of difficult cannulation. A polypectomy snare was used to excise the mucosa covering the surface of the intramural segment of the common bile duct, and a dual knife was used to form a fistula. A guidewire was then inserted through the stoma into the bile duct. After the procedure, the bile duct was successfully cannulated and the stones were removed. No complications occurred. This new method may be an alternative treatment to precutting for difficult biliary cannulation in patients with a protruded papilla of Vater.

Combination of MicroRNAs and Cytokines: a Method for Better Evaluation of Acute-on-Chronic Liver Failure.

BACKGROUND: The aim was to establish expression profiles of microRNAs (miRNAs) in Peripheral Blood Mononuclear Cells (PBMC) and of plasma cytokines from the patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and high-risk of acute-on-chronic liver failure (ACLF) patients as well as healthy people and to examine the relationships between these profiles and clinical features. METHODS: Herein, we collected PBMCs and plasma from peripheral blood of HBV-ACLF and ACLF patients as well as healthy people. Microarray, real-time qPCR, and ELISA assays were used. RESULTS: In this study, we found 39 miRNAs including miR-146a, miR-150, and miR-29a downregulated and 5 miRNAs elevated in PBMCs from HBV-ACLF patients compared to healthy controls. However, elevated plasma levels of cytokines such as TNF-α, IFN-α, and TGF-ß were found in PBMCs from HBV-ACLF patients compared with the controls, but no significant difference was found between the high-risk and control groups. MiR-146a, miR-150, miR-29a, PTA, and anti-HBc were positively correlated with the survival of ACLF patients, while TNFα, IFN-α, INR, and TBiL were negatively correlated with the survival of these patients. CONCLUSIONS: Combined examination of miRNAs in PBMCs and cytokines in plasma together is a better method for monitoring and evaluating HBV-ACLF patients.

Molecular pathogenesis of hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is an inherited iron overload disorder characterized by normal iron-driven erythropoiesis and abnormal iron metabolism, leading to excess iron deposited in parenchymal cells of liver, heart, and endocrine glands. Iron hormone, hepcidin, plays a critical role in iron homeostasis through interaction with ferroportin (FPN), a major cellular iron exporter. Hepcidin is encoded by hepcidin antimicrobial peptide (HAMP). Mutations in hepcidin and any genes that regulate the biology of hepcidin, including hemochromatosis genes (HFE), Hemojuvelin (HJV), transferring receptor 2 (TFR2) and FPN, result in hemochromatosis. The identification of hepcidin and its role will provide a better understanding for pathogenesis of HH.

Primary Malignant Melanoma of the Esophagus With Unusual Endoscopic Findings: A Case Report and Literature Review.

Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. We experienced a 79-year-old man with PMME who had unusual endoscopic findings. On endoscopy, an elongated lump was detected on 1 side of the vertical axis of the esophagus. The mass extended progressively for 15 cm along the esophageal longitudinal axis and invaded half of the esophageal circumference. These endoscopic findings were not characteristic of PMME, and the condition was confirmed with biopsy and immunohistochemical staining. Here, we present this rare case and review the recent relevant literature regarding PMME. Doctors should be aware that PMME might present with unusual endoscopic findings.

Cancer Associated Fibroblast-Derived Hepatocyte Growth Factor Inhibits the Paclitaxel-Induced Apoptosis of Lung Cancer A549 Cells by Up-Regulating the PI3K/Akt and GRP78 Signaling on a Microfluidic Platform.

Tumor stroma and growth factors provide a survival environment to tumor cells and can modulate their chemoresistance by dysregulating several signal pathways. In this study, we fabricated a three-dimensional (3D) microfluidic chip using polydimethylsiloxane (PDMS) to investigate the impact of hepatocyte growth factor (HGF) from cancer-associated fibroblasts (CAF) on the Met/PI3K/AKT activation, glucose regulatory protein (GRP78) expression and the paclitaxel-induced A549 cell apoptosis. With a concentration gradient generator, the assembled chip was able to reconstruct a tumor microenvironment in vitro. We found high levels of HGF in the supernatants of CAF and the CAF matrix from the supernatants of activated HFL1 fibroblasts or HGF enhanced the levels of Met, PI3K and AKT phosphorylation and GRP78 expression in A549 cells cultured in a 3D cell chamber, which was abrogated by anti-HGF. Inhibition of Met attenuated the CAF matrix-enhanced PI3K/AKT phosphorylation and GRP78 expression while inhibition of PI3K reduced GRP78 expression, but not Met phosphorylation in A549 cells. Inhibition of GRP78 failed to modulate the CAF matrix-enhanced Met/PI3K/AKT phosphorylation in A549 cells. Furthermore, inhibition of PI3K or GRP78 enhanced spontaneous and paclitaxel-induced A549 cell apoptosis. Moreover, treatment with the CAF matrix inhibited spontaneous and medium or high dose of paclitaxel-induced A549 cell apoptosis. Inhibition of PI3K or GRP78 attenuated the CAF matrix-mediated inhibition on paclitaxel-induced A549 cell apoptosis. Our data indicated that HGF in the CAF matrix activated the Met/PI3K/AKT and up-regulated GRP78 expression, promoting chemoresistance to paclitaxel-mediated apoptosis in A549 cells. Our findings suggest that the microfluidic system may represent an ideal platform for signaling research and drug screening.

Wilson's disease: a comprehensive review of the molecular mechanisms.

Wilson's disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches.

Endoscopic ultrasound in the diagnosis of mediastinal diseases.

EUS is a useful tool for diagnosis of mediastinal diseases. EUS-FNA plays an important role in staging of lung cancer and in tissue acquisition in patients with mediastinal masses. In this review, the following issues will be addressed: EUS-FNA and EBUS-TBNA, metastatic mediastinal lymph nodes diagnosed by EUS, EUS in assessment of mediastinal lymph node status for staging of lung cancer, mediastinal lymphoma diagnosed by EUS, sarcoidosis and tuberculosis diagnosed by EUS.

Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is increasing in prevalence and is one of the most common cancers in the world. Chief amongst the risks of attaining HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The later has been shown to promote non alcoholic fatty liver disease, which can lead to the inflammatory form non alcoholic steatohepatitis (NASH). NASH is a complex metabolic disorder that can impact greatly on hepatic function. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give an overview of the recent novel mechanisms published that have been associated with NASH and subsequent HCC progression. We will focus our discussion on inflammation and gut derived inflammation and how they contribute to NASH driven HCC.

Meta-analysis of Barrett's esophagus in China.

AIM: To investigate the epidemiology and characteristics of Barrett's esophagus (BE) in China and compare with cases in the west. METHODS: Studies were retrieved from the China National Knowledge Infrastructure and PubMed databases using the terms "Barrett" and "Barrett AND China", respectively, as well as published studies about BE in China from 2000 to 2011. The researchers reviewed the titles and abstracts of all search results to determine whether or not the literature was relevant to the current topic of this research. The references listed in the studies were also searched. Inclusion and exclusion criteria for the literature were appropriately established, and the data reported in the selected studies were analyzed. Finally, a meta-analysis was performed. RESULTS: The current research included 3873 cases of BE from 69 studies. The endoscopic detection rate of BE in China was 1%. The ratio of male to female cases was 1.781 to 1, and the average age of BE patients was 49.07 ± 5.09 years. Island-type and short-segment BE were the most common endoscopic manifestations, accounting for 4.48% and 80.3%, respectively, of all cases studied. Cardiac-type BE was observed in 40.0% of the cases, representing the most common histological characteristic of the condition. Cancer incidence was 1.418 per 1000 person-years. CONCLUSION: Average age of BE patients in China is lower than in Western countries. Endoscopic detection and cancer incidence were also lower in China.