A High-Sensitivity Gravimetric Biosensor Based on S1 Mode Lamb Wave Resonator.

The development of MEMS acoustic resonators meets the increasing demand for in situ detection with a higher performance and smaller size. In this paper, a lithium niobate film-based S1 mode Lamb wave resonator (HF-LWR) for high-sensitivity gravimetric biosensing is proposed. The fabricated resonators, based on a 400-nm X-cut lithium niobate film, showed a resonance frequency over 8 GHz. Moreover, a PMMA layer was used as the mass-sensing layer, to study the performance of the biosensors based on HF-LWRs. Through optimizing the thickness of the lithium niobate film and the electrode configuration, the mass sensitivity of the biosensor could reach up to 74,000 Hz/(ng/cm2), and the maximum value of figure of merit (FOM) was 5.52 × 107, which shows great potential for pushing the performance boundaries of gravimetric-sensitive acoustic biosensors.

M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma.

Tumor-associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2-polarized tumor-associated macrophages (M2-TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2-TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2-TAMs promoted epithelial-mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2-TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM-CSF, tumor necrosis factor-α [TNF-α], ICAM-1, interleukin-6 [IL-6], etc) and chemokines (CCL1, CCL3, etc). In addition, p-AKT (Ser473) and p-PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2-TAMs or treated with M2-TAMs secreted core cytokines (GM-CSF, TNF-α, ICAM-1, and IL-6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2-TAMs. Taken together, the current data indicated that M2-TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway.

The role of a multidisciplinary team in the management of portal hypertension.

BACKGROUND: Gastroesophageal variceal hemorrhage is the most severe complication of portal hypertension, with a high mortality rate. The current recommendations for gastroesophageal varices include pharmacological treatment, endoscopic treatment, transjugular intrahepatic portosystemic shunt (TIPS) placement, and splenectomy with devascularization surgery. Multidisciplinary team (MDT) comprises of a group of medical experts and specialists across a range of disciplines, providing personalized and targeted patient care tailored to each individual's condition, circumstances, and expectations. METHODS: Patients referred to the MDT clinic since its establishment in September 2014 were prospectively enrolled and followed-up for at least 12 months. Patient baseline characteristics, treatment methods, outcome and survival were compared to non-MDT patients retrieved from a prospectively maintained database with propensity score matching. RESULTS: Propensity-score matching (PSM) was carried out to balance available covariates, resulting in 58 MDT patients vs. 111 non-MDT patients. Overall survival and variceal rebleed was compared between the two groups. The rate of variceal rebleed was significantly higher in the non-MDT group, while no difference in overall survival was observed. CONCLUSIONS: This study is the first to investigate the role of a multidisciplinary team in the management of gastroesophageal varices secondary to portal hypertension. Patients treated based on MDT clinic recommendations had a significantly lower risk for variceal rebleed.

Prophylactic use of antibiotics in endoscopic injection of tissue adhesive for the elective treatment of gastric varices: A randomized controlled study.

BACKGROUND: Tissue adhesive injection is the first-line treatment for gastric varices rebleeding. Available studies are focused on antibiotic usage in emergency endoscopy, while the use of antibiotics in selective endoscopic tissue adhesive treatment remains controversial. METHODS: This is a randomized controlled study conducted in a tertiary referral hospital. Consecutive patients were enrolled from February 16, 2016, to November 19, 2016, and blindly randomized into two treatment groups. Patients in the prophylactic group received 2 g of cefotiam during endoscopic injection of tissue adhesive. All the subjects were observed for rebleeding, fever, and changes in laboratory indicators in hospital and post-discharge. RESULT: One hundred and seven patients who received endoscopic therapy for gastroesophageal varices were included. Fifty-three patients were allocated to the antibiotic prophylactic group and 54 patients to the on-demand group. The two groups had similar baseline characteristics. The incidence of fever in hospital was 2/53 (3.8%) vs 9/54 (16.7%) (P = 0.028). Perioperative and postoperative clinical events were significantly lower in the antibiotic prophylactic group (5.7% vs 24.1%, P = 0.018; 7.5% vs 20.4%, P = 0.050). Inflammation indices were elevated on the first day after endoscopic therapy; however, no significant difference was observed between the two groups. The cumulative rebleeding free rate within 2 months was lower in the antibiotic prophylactic group (1.9% vs 9.3%, P = 0.100). CONCLUSION: Our study illustrated that prophylactic use of antibiotics in selective endoscopic injection of tissue adhesive reduced the incidence of the total clinical events in perioperative period and had a trend towards lower rebleeding in 2 months.

Asparaginyl endopeptidase may promote liver sinusoidal endothelial cell angiogenesis via PI3K/Akt pathway.

BACKGROUND AND AIMS: pathological angiogenesis plays an important role in the progression of chronic liver diseases. Asparaginyl endopeptidase (AEP) participates in tumor angiogenesis and was recently shown to be associated with liver fibrosis. This study aimed to explore the effect of AEP on liver sinusoidal endothelial cell (LSECs) angiogenesis and determine the underlying mechanism. METHODS: cultured LSECs were infected with lentiviruses in order to suppress AEP expression (AEP-KD1, AEP-KD2). The effect of AEP on LSECs proliferation, apoptosis and migration were subsequently determined by a CCK8 assay, flow cytometry and wound-healing and Transwell assays, respectively, in AEP knocked-down and control LSECs. The expression of the endothelial cell surface markers CD31, CD34 and von Willebrand factor (vWF) were detected by immunofluorescence assay and western blot. The angiogenic factors, vascular endothelial growth factor receptor 2 (VEGFR2) and interleukin 8 (IL 8) were detected by real-time PCR and western blot. The effect of AEP on vessel tube formation by LSECs was examined by Matrigel™ tube-formation assay. Phosphoinositide 3-kinase (PI3K)/Akt expression and phosphorylation were detected by western blot. RESULTS: AEP was effectively knocked down by lentivirus infection in LSECs. Down-regulation of AEP expression significantly decreased proliferation and migration and increased apoptosis of LSECs. Moreover, expression levels of the endothelial cell surface markers CD31, CD34 and vWF, as well as angiogenic factors VEGFR2 and IL 8, were also reduced after AEP was knocked-down. The vessel tube formation abilities of AEP-KD1 and AEP-KD2 LSECs were significantly inhibited compared with LSECs without AEP knocked-down. Down-regulation of AEP also inhibited the phosphorylation of PI3K and Akt. CONCLUSION: AEP promotes LSECs angiogenesis in vitro, possibly via the PI3K/Akt pathway. AEP may therefore be a potential therapeutic target for preventing the progression of liver fibrosis.

Endoscopic cyanoacrylate injection with or without lauromacrogol for gastric varices: A randomized pilot study.

BACKGROUND AND AIM: Current guidelines recommend injection of cyanoacrylate as first-line therapy to prevent gastric variceal rebleeding. The method still poses a risk of ectopic embolism, which possibly correlates with the volume of cyanoacrylate used. In this trial, we evaluated the short-term efficacy and safety of tissue adhesive injection combined with lauromacrogol for treating gastric varices. METHODS: Patients admitted to our hospital for variceal hemorrhage were enrolled and blindly randomized into two treatment groups: lauromacrogol group (lauromacrogol-cyanoacrylate-lauromacrogol) and lipiodol group (lipiodol-cyanoacrylate-lipiodol). Patient follow-up was 6 months. Primary outcome was rebleeds, and secondary outcomes were mortality, gastric varices eradication, and treatment-related adverse events. RESULTS: Between March 6, 2013 and October 16, 2013, 96 patients met the criteria. Two cases were lost to follow-up, and all treated cases were successful. No procedural-related adverse events were observed in either group. Cyanoacrylate volumes used in the lauromacrogol group were significantly less than those of the lipiodol group (0.9 ± 0.5 vs 2.0 ± 1.2 mL, P = 0.000). Eleven patients developed upper gastrointestinal rebleeding, which did not show significant difference between groups. On multivaritate analysis, portal venous thrombosis and fever were potential risk factors of rebleeding. Treatment failure, complications, gastric varices obturation, and survival did not differ between the two groups. CONCLUSION: Tissue adhesives combined with lauromacrogol is a safe therapeutic option for gastric varices, with comparably less cyanoacrylate volume used. Because of the small number of study patients, it cannot be proven to have better efficacy than without lauromacrogol. Multicenter studies with larger patient groups are necessary.

A Fast Superpixel Segmentation Algorithm for PolSAR Images Based on Edge Refinement and Revised Wishart Distance.

The superpixel segmentation algorithm, as a preprocessing technique, should show good performance in fast segmentation speed, accurate boundary adherence and homogeneous regularity. A fast superpixel segmentation algorithm by iterative edge refinement (IER) works well on optical images. However, it may generate poor superpixels for Polarimetric synthetic aperture radar (PolSAR) images due to the influence of strong speckle noise and many small-sized or slim regions. To solve these problems, we utilized a fast revised Wishart distance instead of Euclidean distance in the local relabeling of unstable pixels, and initialized unstable pixels as all the pixels substituted for the initial grid edge pixels in the initialization step. Then, postprocessing with the dissimilarity measure is employed to remove the generated small isolated regions as well as to preserve strong point targets. Finally, the superiority of the proposed algorithm is validated with extensive experiments on four simulated and two real-world PolSAR images from Experimental Synthetic Aperture Radar (ESAR) and Airborne Synthetic Aperture Radar (AirSAR) data sets, which demonstrate that the proposed method shows better performance with respect to several commonly used evaluation measures, even with about nine times higher computational efficiency, as well as fine boundary adherence and strong point targets preservation, compared with three state-of-the-art methods.

Simvastatin suppresses the proangiogenic microenvironment of human hepatic stellate cells via the Kruppel-like factor 2 pathway.

BACKGROUND AND AIMS: Statins are reported to have a beneficial effect on portal hypertension (PTH); however, the exact mechanism remains unknown. Hepatic stellate cells (HSCs) can be activated by transforming growth factor beta (TGFâ) and play an important role in angiogenesis leading to PTH. Statins potently stimulate the transcription factor, Kruppel-like factor 2 (KLF2), which can negatively regulate angiogenesis. Our present study aimed to investigate the anti-angiogenic potential of statins in HSCs through the KLF2 pathway. METHOD: TGFâ-induced human HSCs were exposed to simvastatin. Cell viability and proliferation were determined by MTT and BrdU-proliferation assays, respectively. Cell migration was investigated using a transwell and wound-healing assays. Gene quantification was measured by real-time polymerase chain reaction. Protein expression was detected by western blot analysis and immunohistochemistry. Inflammatory factors were measured using enzyme-linked immunosorbent assays. RESULT: Simvastatin was found to reduced cell migration and proliferation and inhibit expression of alpha smooth muscle actin in TGFâ-induced HSCs. Furthermore, simvastatin promoted already increased mRNA and protein levels of KLF2 in TGFâ-induced HSCs. In accordance with KLF2 overexpression, simvastatin increased production of endothelial nitric oxide synthesis (eNOS) and downregulated expression of some proangiogenic proteins, such as vascular endothelial growth factor, hypoxia inducible factor-1a and nuclear factor-kappa B in TGFâ-induced HSCs. At the same time, secretion of interferon-gamma increased in TGFâ induced HSCs, which was decreased by simultaneous addition of simvastatin. CONCLUSION: Simvastatin suppressed the proangiogenic environment of HSCs activated by TGFâ, and KLF2 pathway is involved in the course.

HER2 mRNA status contributes to the discrepancy between gene amplification and protein overexpression in gastric cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an important proto-oncogene of prognostic use in gastric cancer (GC). Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the main clinical methods of detection of HER2, but consistency between the methods is poor and the cause of the discrepancy is unclear. AIM: To investigate the involvement of HER2 mRNA status in the disparity between gene amplification and protein overexpression. METHODS: We investigated HER2 gene, mRNA, and protein profiles in gastric precancer and cancer tissues by use of the molecular approaches FISH, real-time polymerase chain reaction, and IHC. The relationships between HER2 and matrix metalloproteinase 9 (MMP9) and Smad7 expression were analyzed and the involvement of HER2 in the interaction between tumor cells and lymphocytes was investigated by coculturing GC cell lines with peripheral blood mononuclear cells (PBMCs). RESULTS: HER2 protein expression was significantly increased in cancer compared with precancer (P = 0.003), and the corresponding mRNA levels were significantly lower in precancer and cancer tissues than in normal tissues (κ = 0.290, P = 0.025). HER2 mRNA levels were significantly higher in tumor than in peritumor tissue (P = 0.028), and were positively correlated with MMP9 and Smad7 mRNA levels in tumor tissues. HER2 mRNA expression in GC cell lines was increased by coculture with PBMCs. CONCLUSIONS: Different HER2 mRNA profiles, possibly in relation to contact between tumor cells and lymphocytes, might help to explain the discrepancy between gene amplification and protein overexpression results.

Rescue treatment with add-on efgartigimod in a patient with impending myasthenic crisis: a case report.

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness. Severe patients may develop life-threatening respiratory failure and experience crisis. Plasma exchange or intravenous immunoglobulin (IVIg) is the first-line treatment option for myasthenia crisis, but some patients still poorly respond to them. Here, we first reported a generalized MG patient from China who was in a state of impending myasthenic crisis and did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. Especially, we also detected meaningful changes in T-cell and B-cell subsets after efgartigimod, promoting a potential role of efgartigimod in re-establishing immune homeostasis.

Increased serum interleukin-41 correlates with disease severity in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease mediated by pathogenic antibodies produced by abnormally activated B cells, resulting in neuromuscular junction transmission dysfunction. Interleukin-41 (IL-41) is a novel immunomodulatory cytokine that has been implicated in various metabolic, inflammatory, and autoimmune diseases. The role of IL-41 in MG is still unclear up to now, our study aimed to investigate the level of IL-41 in MG patients and its correlation with clinical features and inflammatory indicators. METHODS: Totally, 60 MG patients and 30 healthy controls (HC) were recruited. Baseline data and laboratory parameters were routinely recorded through electronic medical systems. IL-41 levels were measured by enzyme-linked immunosorbent assay. Proportions of T-cell and B-cell subsets and natural killer cells were analyzed by flow cytometry. The correlation between serum IL-41 and MG related parameters was investigated, and the clinical value of IL-41 in the diagnosis of MG was evaluated by receiver operator characteristic curve (ROC) analysis. RESULTS: Serum IL-41 levels in MG patients were higher than in HC, and were higher in Myasthenia Gravis Foundation of America (MGFA) III + IV group than that in MGFA I + II group. Serum IL-41 was positively correlated with MG-specific activities of daily living scale (MG-ADL), MGFA classification, platelet to lymphocyte ratio (PLR), and proportion of CD19+ B cells, while it was negatively correlated with high-sensitive C-reactive protein (hs-CRP) and circulatory plasma cells in MG patients. Serum IL-41 levels increased in patients who were treated with efgartigimod during the first cycle of therapy. However, compared to disease initiation, serum IL-41 levels decreased when clinical features steadily improved. ROC analysis showed that IL-41 had a diagnostic value for MG. CONCLUSION: The present findings suggested that serum IL-41 was increased in MG patients and was positively associated with the severity of the disease. IL-41 may be essential to the immunopathological mechanism of MG and a potential biomarker for MG.

Comparative effectiveness of warfarin in cirrhotic patients with non-symptomatic portal vein thrombosis: a multicenter, randomized controlled trial.

The effectiveness and risks of anticoagulant therapy in cirrhotic patients with non-symptomatic portal vein thrombosis (PVT) remain unclear. We conducted a multicenter, Zelen-designed randomized controlled trial to determine the effectiveness of warfarin in cirrhotic patients with non-symptomatic PVT during a one-year follow-up. In brief, 64 patients were 1:1 randomly divided into the anticoagulation group or the untreated group. The probability of recanalization was significantly higher in the anticoagulation group than those untreated in both ITT analysis (71.9% vs 34.4%, p = 0.004) and PP analysis (76.7% vs 32.4%, p < 0.001). Anticoagulation treatment was the independent predictor of recanalization (HR 2.776, 95%CI 1.307-5.893, p = 0.008). The risk of bleeding events and mortality were not significantly different. A significantly higher incidence of ascites aggravation was observed in the untreated group (3.3% vs 26.5%, p = 0.015). In conclusion, warfarin was proved to be an effective and safe as an anticoagulation therapy for treating non-symptomatic PVT in cirrhotic patients.

FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway.

Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

Network cluster analysis of protein-protein interaction network identified biomarker for early onset colorectal cancer.

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world. However, the genetic alterations and molecular mechanism of the early onset CRCs are not fully investigated. The present study aimed to characterize early onset CRC by analyzing its gene expression compared with normal controls and to identify network-based biomarkers of early onset CRC. The gene expression profiles of early onset CRC were downloaded from Gene Expression Omnibus and the differentially expressed genes (DEGs) in CRC patients were identified. Then, a protein-protein interaction (PPI) network was constructed and the clusters in PPI were analyzed by ClusterONE. Furthermore, the gene ontology functional analysis and pathway enrichment analysis were conducted to the modules in PPI network. A systems biology approach integrating microarray data and PPI was further applied to construct a PPI network in CRC. Total 631 DEGs were identified from the early onset CRC compared to healthy controls. These genes were found to be involved in several biological processes, including cell communication, cell proliferation, cell shape and apoptosis. Five functional modules which may play important roles in the initiation of early onset CRC were identified from the PPI network. Functional annotation revealed that these five modules were involved in the pathways of signal transduction, carcinogenesis and metastasis. The hub nodes of these five modules, CDC42, TEX11, QKI, CAV1 and FN1, may serve as the biomarkers of early onset CRC and have the potential to be targets for therapeutic intervention. However, further investigations are still needed to confirm our findings.

Design and Analysis of Lithium-Niobate-Based Laterally Excited Bulk Acoustic Wave Resonator with Pentagon Spiral Electrodes.

In this paper, we present a comprehensive study on the propagation and dispersion characteristics of A1 mode propagating in Z-cut LiNbO3 membrane. The A1 mode resonators with pentagon spiral electrodes utilizing Z-cut lithium niobate (LiNbO3) thin film are designed and fabricated. The proposed structure excites the A1 mode waves in both x- and y-direction by utilizing both the piezoelectric constants e24 and e15 due to applying voltage along both the x- and y-direction by arranging pentagon spiral electrode. The fabricated resonator operates at 5.43 GHz with no spurious mode and effective electromechanical coupling coefficient (Keff2) of 21.3%, when the width of electrode is 1 µm and the pitch is 5 µm. Moreover, we present a comprehensive study of the effect of different structure parameters on resonance frequency and Keff2 of XBAR. The Keff2 keeps a constant with varied thickness of LiNbO3 thin film and different electrode rotation angles, while it declines with the increase of p from 5 to 20 µm. The proposed XBAR with pentagon spiral electrodes realize high frequency response with no spurious mode and tunable Keff2, which shows promising prospects to satisfy the needs of various 5 G high-band application.

New Insights into Alzheimer's Disease: Novel Pathogenesis, Drug Target and Delivery.

Alzheimer's disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid ß protein (Aß) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aß and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aß cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aß aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aß- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood-brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aß-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aß assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage.

Aluminum Nitride-Based Adjustable Effective Electromechanical Coupling Coefficient Film Bulk Acoustic Resonator.

The arrival of the 5G era has promoted the need for filters of different bandwidths. Thin-film bulk acoustic resonators have become the mainstream product for applications due to their excellent performance. The Keff2 of the FBAR greatly influences the bandwidth of the filter. In this paper, we designed an AlN-based adjustable Keff2 FBAR by designing parallel capacitors around the active area of the resonator. The parallel capacitance is introduced through the support column structure, which is compatible with conventional FBAR processes. The effects of different support column widths on Keff2 were verified by finite element simulation and experimental fabrication. The measured results show that the designed FBAR with support columns can achieve a Keff2 value that is 25.9% adjustable.

Preparation, Characterization, and Application of AlN/ScAlN Composite Thin Films.

Piezoelectric aluminum nitride (AlN) thin film, as a commonly used material for high-frequency acoustic resonators, has been a research hotspot in the RF field. Doping Sc elements in AlN is one of most effective methods to improve the piezoelectricity of the material. In this work, the first principal calculation and Mori-Tanaka model are used to obtain the piezoelectric constants of AlN, ScAlN, and AlN/ScAlN composites. Then, five types of AlN/ScAlN thin films are prepared on 8 inch silicon substrates. The crystal quality, roughness, and stress distribution are measured to characterize the film quality. The results show that composite film can effectively solve the problem of abnormal grains and reduce the roughness. Finally, a lamb wave resonator with an AlN/Sc0.2Al0.8N composite working at 2.33 GHz is fabricated. The effective electromechanical coupling coefficient Keff2 is calculated to be 6.19%, which has the potential to design high-frequency broadband filters.

Involvement of V-Ets erythroblastosis virus E26 oncogene homolog 2 in regulation of transcription activity of MDR1 gene.

Over-expression of MDR1 confers multidrug resistance (MDR) in cancers and remains a major cause for the failure of chemotherapy. In the present study, we found that V-Ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) could activate MDR1 transcription and P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of ETS2 attenuated MDR1 transcription and P-gp expression, and increased the sensitivity of MDR cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. ETS2 could bind to the ETS2 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by ETS2 may provide potential ways to overcome MDR in cancer treatment.

Laryngoscopy findings and histological results in a rabbit gastroesophageal reflux model.

The role of lower esophageal sphincter (LES) in laryngopharyngeal reflux is controversial. In this study, we used an animal model to investigate the association between LES dysfunction and reflux laryngitis. Twelve healthy New Zealand albino rabbits (2.5-3.5 kg) were utilized in this study. The animals were divided into two groups. Eight rabbits underwent total cardiomyectomy to induce reflux, and the remaining four rabbits underwent a control sham operation. A laryngoscopy and a 24-hour intra-esophageal pH-metry were performed prior to surgery and again 2 and 8 weeks postsurgery. After the final laryngoscopy, all animals were sacrificed to obtain histological results. Total cardiomyectomy significantly increased the reflux index, the duration of the longest reflux episode and the total number of episodes that occurred in 24 h postsurgery. No significant difference was observed in the reflux finding score (RFS) between preoperative and 2-week postoperative rabbits (P = 0.11). But there was a statistically significant change in the RFS before and 8 weeks after the induction of reflux from 4.6 ± 0.9 to 8.3 ± 3.6 (P = 0.02). Submucous gland hyperplasia and inflammation were significantly increased in the reflux group compared to the control group. The results of this study suggest that chronic lower esophageal sphincter dysfunction is associated with reflux laryngitis in rabbits.