Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Sulfonated GO coated carbon electrodes with cation-selective functions for enhanced capacitive deionization of saltwater.

Deionization of salt, contaminated underground and inorganic waste waters for water recycling and reuse is of increasing importance mainly due to the shortage of freshwater worldwide. Membrane capacitive deionization (MCDI) possessing a high electrosorption capacity and energy efficiency has been considered a promising method for desalination. However, the MCDI reaction system has limited applications because of the high interfacial resistance during operation. In the present work, the novel sulfonated graphene oxide (SGO) serving as a hydrophilic cation exchange membrane that was coated directly on the activated carbon (AC) electrode was prepared to enhance capacitive deionization of saltwater. Experimentally, the electrosorption capacity and charge efficiency of the AC/SGO (negative)||AC (positive) electrode pair using the coated SGO thin film increased from 12.8 to 19.8 mg/g and 56.7 to 89.3%, respectively. The enhancements were associated with the reduction of the co-ion effect during electrosorption. The strong negative PhSO3- group grafted on the SGO thin film could selectively accelerate the transport rate of cations during CDI. The increase of the charge efficiency also led to lower implemented current. This work demonstrates a simple, low-cost and effective desalination method that will likely have many new applications especially in water recycling and reuse.

Efficacy of Kanglaite against radiotherapy-induced mucositis in head and neck cancer, a phase II trial.

PURPOSE: To explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: This was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3-4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy. RESULTS: The data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions. CONCLUSIONS: A low incidence of grade 3-4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer.

Hemogram-based decision tree for predicting the metabolic syndrome and cardiovascular diseases in the elderly.

BACKGROUND: This study aimed to build a hemogram-based decision tree to evaluate the association between current probability of metabolic syndrome (MetS) and prediction of future hypertension, type 2 diabetes and cardiovascular diseases (CVD) risk. METHODS: A total of 40 395 elder participants (≥60 years) were enrolled in a standard health examination program in Taiwan from January 1999 to December 2014. A decision tree classification of the presence or absence of MetS at baseline, using age, sex and hemogram (white blood cell, hemoglobin and platelet) as independent variables, was conducted for the randomly assigned training (70%) and validation (30%) groups. Participants without MetS at baseline (n = 25 643) were followed up to observe whether they developed MetS, hypertension, type 2 diabetes or CVD in the future. RESULTS: Modest accuracy of the decision tree in the training and validation groups with area under the curves of 0.653 and 0.652, respectively, indicated an acceptable generalizability of results. The predicted probability of baseline MetS was obtained from decision tree analysis. Participants without MetS at baseline were categorized into three equally sized groups according to the predicted probability. Participants in the third tertile had significantly higher risks of future MetS (hazard ratio 1.40, 95% confidence interval 1.25-1.58); type 2 diabetes (1.46, 1.17-1.83); hypertension (1.14, 1.01-1.28); and CVD (1.21, 1.01-1.44), compared with those in the first tertile. CONCLUSIONS: Execution of hemogram-based decision tree analysis can assist in early identification and prompt management of elderly patients at a high risk of future hypertension, type 2 diabetes and CVD.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.

Effect of levocarnitine on cerebral ischemia-reperfusion rats via activating Nrf2/ARE signaling pathway.

OBJECTIVE: Levocarnitine plays a crucial role in the metabolism of organisms. The aim of this study was to explore the impact of Levocarnitine on cerebral ischemia-reperfusion (I/R) rats and the underlying mechanism. MATERIALS AND METHODS: Cerebral I/R model was first successfully established. Two groups were set up, including drug group (I/R + Levocarnitine group) and control group (I/R group). The influences of Levocarnitine on brain injury and oxidative stress in cerebral I/R rats were evaluated. Furthermore, the impacts of Levocarnitine on the nuclear factor E2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway and neuronal apoptosis in rats were detected. RESULTS: Compared with I/R group, I/R + Levocarnitine group exhibited markedly lowered neurological deficit score and cerebral infarct volume. However, superoxide dismutase (SOD) and notably decreased malondialdehyde (MDA) were significantly up-regulated in I/R + Levocarnitine group. This suggested that Levocarnitine could relieve cerebral nerve injury and oxidative stress in cerebral I/R rats. Additionally, in I/R + Levocarnitine group, the protein expressions of Nrf2, heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (Bcl-2) were significantly up-regulated, whereas cleaved Caspase-3 (c-Caspase-3) was notably down-regulated. Furthermore, neuronal apoptosis in cerebral I/R rats was remarkably inhibited. CONCLUSIONS: Levocarnitine alleviates brain injury and neuronal apoptosis in cerebral I/R rats by activating the Nrf2/ARE signaling pathway.

Whole genome expression microarray reveals novel roles for Kif4 in monocyte/macrophage cells.

OBJECTIVE: Kinesin superfamily member 4 (Kif4), a conventional kinesin, is a microtubule-dependent molecular motor. The active movement of Kif4 participates in several cellular functions, including DNA repair, mitosis, the transport of macromolecules, survival of neurons and even tumorigenesis and progression. However, the role of Kif4 in monocyte/macrophage cells has not been reported. Our work aimed to increase understanding and further investigations of Kif4 in monocyte/macrophage cells. MATERIALS AND METHODS: RAW264.7 cells were transfected with Kif4 small interfering RNA (siRNA), and whole genome expression microarray analysis was employed to analyze gene expression after cells treatment with or without Kif4 siRNA. RESULTS: Our data found multiple differentially expressed genes which were enriched in the top 5 biological processes about innate immune response, immune response, response to interferon-beta, immune system process and cellular response to interferon-beta. 23 most significant pathways had been identified and enriched pathways indicated enrichment in peroxisome, lysosome, fatty acid metabolism, cell adhesion molecules and so on. CONCLUSIONS: Our work may help understand the roles of Kif4 in monocyte/macrophage cells and would give useful information on basic research and the function of monocyte/macrophage cells.

The Cuffless Blood Pressure Measurement with Multi-dimension Regression Model based on Characteristics of Pulse Waveform.

According to the advancement of wearable technology, many physiological monitoring instruments are gradually converted into wearable devices. But, the blood pressure monitor still is a cuff-type device in the consumer market, which also does not do the beat-by-beat continuous blood pressure measurement. Now, the cuffless blood pressure measurement has been developed based on the pulse transit time (PTT) but its accuracy is not better. According to the cardiac hemodynamic theorem, the blood pressure relates with the arterial characteristics. Therefore, the purpose of this study was to use the characteristics of the pulse wave measured by photoplethysmography (PPG) to estimate the blood pressure with a multi-dimension regression model. The contour of pulse wave includes some characteristics of the artery. There were 10 subjects participating the experiment, and the blood pressure of the subject was changed by the exercise. The results showed that the cumulate root mean square error of the estimated systolic and diastolic pressures with the multi-parameters were 69.3 mmHg and 39.8 mmHg were better than only using one parameter, PTT, 82.1 mmHg and 45.2 mmHg, respectively.

Tyrosine kinase Pyk2 is involved in colonic smooth muscle contraction via the RhoA/ROCK pathway.

The contraction of gastrointestinal (GI) smooth muscles is regulated by both Ca(2+)-dependent and Ca(2+) sensitization mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in the depolarization-induced contraction of vascular smooth muscle via a Ca(2+) sensitization pathway. However, the role of Pyk2 in GI smooth muscle contraction is unclear. The spontaneous contraction of colonic smooth muscle was measured by using isometric force transducers. Protein and phosphorylation levels were determined by using western blotting. Pyk2 protein was expressed in colonic tissue, and spontaneous colonic contractions were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of tetrodotoxin (TTX). In cultured colonic smooth muscle cells (CSMCs), PF-431396 decreased the levels of myosin light chain (MLC20) phosphorylated at Ser19 and ROCK2 protein expression, but myosin light chain kinase (MLCK) expression was not altered. However, Y-27632, a Rho kinase inhibitor, increased phosphorylation of Pyk2 at Tyr402 and concomitantly decreased ROCK2 levels; the expression of MLCK in CSMCs did not change. The expression of P(Tyr402)-Pyk2 and ROCK2 was increased when CSMCs were treated with Ach. Pyk2 is involved in the process of colonic smooth muscle contraction through the RhoA/ROCK pathway. These pathways may provide very important targets for investigating GI motility disorders.

Expression of Kif5b protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma.

OBJECTIVE: Kinesin family member 5b (Kif5b), a conventional kinesin, mainly participates in lysosome and mitochondria transportation. Some studies have indicated that Kif5b may be associated with the development of a variety of tumors. However, the role Kif5b plays in oral squamous cell carcinoma (OSCC) has yet to be determined. Our study aimed at investigating the expression level of Kif5b in primary OSCC and discussing its clinical significance in patients' outcomes. PATIENTS AND METHODS: We measured Kif5b expression in 82 OSCC tissue samples with immunohistochemistry. The associations between the expression level of Kif5b and clinicopathological characteristics as well as patients' survival were statistically assessed. RESULTS: Kif5b level was significantly associated with tumor size (p=0.034), histological differentiation (p=0.028), disease recurrence (p=0.018), surrounding tissue invasion (p=0.045), recurrence time (p=0.036) and survival status (p=0.030). Kaplan-Meier cumulative survival analyses indicated that high expression of Kif5b was linked to worse overall survival (p=0.0112) and disease-free survival (p=0.0085). The univariate and multivariate Cox proportional hazard analysis further identified the expression status of Kif5b as an independent variable that correlated with patients' survival and recurrence. Furthermore, in 54 early-stage, clinically node negative OSCC patients, Kif5b expression were correlated with histological differentiation (p=0.034), disease recurrence (p=0.038) and surrounding tissue invasion (p=0.029). Univariate and multivariable logistic regression results showed that only Kif5b expression level could influence the probability of recurrence. CONCLUSIONS: Our results reveal that Kif5b expression is associated with poor clinical outcome in OSCC and even in early-stage, clinically node negative OSCC and may be a potential target for OSCC treatment.

Patterns of intra-articular injection use after initiation of treatment in patients with knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: We sought to describe and evaluate longitudinal use of intra-articular injections after treatment initiation among adults with radiographically confirmed knee osteoarthritis (OA). METHOD: Using data from the Osteoarthritis Initiative (OAI), we included participants with radiographically confirmed OA (Kellgren-Lawrence grade (K-L) ≥ 2) in ≥1 knee at baseline. With 9 years of data, 412 participants newly initiating hyaluronic acid or corticosteroid injections with their index visit were identified. For each type of injection initiated, socio-demographic and clinical characteristics were described by patterns of treatments (one-time use, switched, or continued injections). Multinomial logistic models estimated the extent to which patient-reported symptoms (post-initial injection and changes over time) were associated with patterns of injection use. RESULTS: Of those initiating injections, ∼19% switched, ∼21% continued injection type, and ∼60% did not report any additional injections. For participants initiating corticosteroid injections, greater symptoms post-initial injection were associated with lower odds of continued use compared to one-time users (adjusted odds ratio (aOR) for Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain: 0.91; 95%, confidence interval (CI): 0.83 to 0.99; aORstiffness: 0.77; CI: 0.63 to 0.94; aORphysical function: 0.97; CI: 0.94 to 1.00). Symptom changes over time (e.g., worsened or improved) were not associated with patterns of injections use. CONCLUSION: After treatment initiation, the proportion of patients switching injection use and one-time users was substantial. Symptoms post-initial injection appear to be associated with patterns of injection use. The extent to which these patterns are an indication of lack of impact on patient-reported symptoms should be explored.

Infragradación de la biopsia de próstata respecto a la pieza de prostatectomía la población china: nomogramas actualizados / Gleason sum upgrading between biopsy and radical prostatectomy in Chinese population: updated nomograms

Introducción: Evaluar los factores de riesgo de la supragraduación de la suma de Gleason en la prostatectomía radical (PR) y actualizar el nomograma para la predicción de la infragraduación de la biopsia respecto a la pieza de prostatectomía radical. Métodos: La cohorte del estudio consistió en 237 pacientes chinos con adenocarcinoma de próstata que fueron sometidos a biopsia de próstata de 10 cilindros y posteriormente fueron sometidos PR en el Hospital Huashan, entre febrero de 2011 y mayo de 2015. El principal objetivo de nuestro estudio fue el estudio de la supragraduación de la suma de Gleason respecto a la biopsia en la muestra de PR. Se realizaron modelos de regresión logística univariante y multivariante para explorar los potenciales factores predictivos, y en última instancia para construir los nomogramas. El modelo de predicción se evaluó por su capacidad para predecir la supragraduación significativa en pacientes con suma de Gleason de biopsia < 8. Resultados: En la cohorte principal se observó supragraduación de la suma de Gleason en 62 (26,16%) pacientes. El nivel de antígeno específico de próstata (PSA) preoperatorio, la suma de Gleason de biopsia y el tacto rectal se utilizaron en la construcción del nomograma, que fue validado internamente con un índice de concordancia corregido por bootstrap de 0,787. En la subcohorte de 115 pacientes con datos estandarizados de biopsia se observó supragraduación en 31 (26,96%) pacientes. El nivel preoperatorio de PSA, suma de Gleason de biopsia y el número de cilindros positivos se utilizaron en el nomograma, que también fue validado internamente con un índice de concordancia de corregido por bootstrap de 0,833. Estos 2 nomogramas demostraron un rendimiento estadístico satisfactorio para predecir supragraduación significativa. Conclusiones: Se desarrollaron nomogramas actualizados para predecir la supragraduación de la suma de Gleason de la biopsia respecto a la PR, que demostraron un buen rendimiento estadístico tras la validación interna

Introduction: To assess the risk factors of Gleason sum upgrading between biopsy and radical prostatectomy (RP) and update the nomogram for the prediction of Gleason sum upgrading. Methods: The study cohort consisted of 237 Chinese prostate adenocarcinoma patients who underwent 10-core prostate biopsy and subsequently received RP in Huashan Hospital from February 2011 to May 2015. The main outcome of our study was Gleason sum upgrading between biopsy and RP pathology. Univariate and multivariate logistic regression models were conducted to explore the potential predictors, and ultimately to build the nomograms. The prediction model was further evaluated for its ability to predict significant upgrading in patients with biopsy Gleason sum < 8. Results: In the main cohort of all the patients, Gleason sum upgrading was observed in 62 (26.16%) patients. The pre-operative prostate-specific antigen (PSA) level, biopsy Gleason sum, and digital rectal examination were used in building the nomogram, which was validated internally with a bootstrap-corrected concordance index of 0.787. In the sub-cohort of 115 patients with standardized biopsy details, Gleason sum upgrading was observed in 31 (26.96%) patients. The pre-operative PSA level, biopsy Gleason sum, and number of positive cores were used in the nomogram, which was also validated internally with a bootstrap-corrected concordance index of 0.833. These two nomograms both demonstrated satisfactory statistical performance for predicting significant upgrading. Conclusions: Updated nomograms to predict Gleason sum upgrading in Chinese population between biopsy and RP were developed, demonstrating good statistical performance upon internal validation

Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells.

Metastasis of the cervical lymph nodes frequently leads to poor survival of patients with oral squamous cell carcinoma (OSCC). The underlying mechanisms of lymph node metastasis are unclear. Wingless-type MMTV integration site family, member 5B (WNT5B), one component of the WNT signal pathway, was markedly up-regulated in OSCC sublines with high potential of lymphatic metastasis compared to that in OSCC cells with low nodal metastasis. Increased WNT5B mRNA was demonstrated in human OSCC tissues in comparison with adjacent non-tumorous tissues. Interestingly, the high level of WNT5B protein in serum was associated with lymph node metastasis in OSCC patients. Knockdown of WNT5B expression in OSCC sublines did not affect tumour growth but impaired lymph node metastasis and tumour lymphangiogenesis of orthotopic transplantation. Conditioned medium from WNT5B knockdown cells reduced the tube formation of lymphatic endothelial cells (LECs). In contrast, recombinant WNT5B enhanced the tube formation, permeability and migration of LECs. In LECs stained with phalloidin, the morphology of those treated with recombinant WNT5B changed from flat to spindle-like. Recombinant WNT5B also increased α-smooth muscle actin and inhibited the expression of vascular endothelial-cadherin but retained characteristics of endothelial cells. The results suggest that WNT5B functions in the partial endothelial-mesenchymal transition (EndoMT). Furthermore, WNT5B-induced tube formation was impaired in the LECs following the knockdown of EndoMT-related transcription factor, SNAIL or SLUG. The WNT5B-induced expression of Snail or Slug was abolished by IWR-1-endo and Rac1 inhibitors, which are involved in the WNT/ß-catenin and planar cell polarity pathways, respectively. Collectively, the data suggest that WNT5B induces tube formation by regulating the expression of Snail and Slug proteins through activation of canonical and non-canonical WNT signalling pathways.

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE: To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS: In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.

Efficacy of sclerotherapy with radio-opaque foam guided by digital subtraction angiography for the treatment of complex venous malformations of the head and neck.

Our aim was to evaluate the efficacy of sclerotherapy using radio-opaque foam and guided by digital subtraction angiography (DSA) for complex venous malformations in the head and neck in 11 selected patients between 2011 and 2013. The sclerosing foam was manufactured by the classic Tessari method and consisted of air, 1% polidocanol, and radio-opaque media iopromide (Ultravist(®)300) in a ratio of 7:2:1. We recorded the site and size of the lesion, time and duration of treatment, and therapeutic response. The lesions were on the face, cheek, temporal region, parotid region, neck, tongue, floor of the mouth, parapharyngeal space, and soft palate. The sclerosing foam was radio-opaque under DSA, and the mean (range) dose was 21 (3-65) ml. A mean (range) of 4 (2-7) treatments was required, and 10 of the 11 patients responded well. In 4 of the 11 cases the lesion resolved completely and in 6 there was a good response. Only one lesion recurred. Early complications included immediate swelling in injected areas, snoring, and pain on swallowing, but there were no air emboli or signs of cutaneous necrosis, and the complications were self-limiting. DSA-guided sclerotherapy with radio-opaque foam was safe and effective for the treatment of complex vascular malformations of the head and neck.

Mortality and cost of radiation therapy for oesophageal cancer according to hospital accreditation level: a nationwide population-based study.

This study examined and analysed the relationship between the cost-effectiveness and outcome of radiotherapy for oesophageal cancer among hospitals with varying accreditation levels. We selected 428 oesophageal cancer patients from medical and non-medical centres using the National Health Insurance Research Database, which is maintained by the Taiwanese National Health Research Institutes, and compared their medical expenditure and the outcome of their radiotherapy treatment. In this study cohort of patients with oesophageal cancer, 278 patients were treated in medical centres (mean age: 60.1 years) and 150 patients were treated in non-medical centres (mean age: 62.0 years, P = 0.16). The medical centre group exhibited significantly lower medical expenses, mortality and risk of death compared with the non-medical centre group (adjusted hazard ratio = 1.38, 95% confidence interval = 1.11-1.71). Our study determined that radiotherapy for oesophageal cancer costs significantly less, and medical centres had lower mortality rates than non-medical centres. These findings could provide professional organisations and healthcare policy makers with essential information for allocation of resources.