Search

Purpose: The study was aimed to examine components and provider’s characteristics of non-pharmacological intervention that affect delirium prevention in elderly inpatients. Additional effects on delirium prevention based on identified characteristics were explored.Methods: Studies were searched by using seven electronic databases and examined through Preferred Reporting Items Systematic Review and Meta-Analysis (PRISMA) flow diagram. The Risk of Bias (ROB) and the Risk of Bias Assessment tool for Non-randomized Study (RoBANS) were used to evaluate the quality of each included study.Results: Seven studies were selected for the systematic review. Most of the selected studies had a low risk of bias. Interventions of each study and delirium outcome were heterogeneous. Each multi-component non-pharmacological intervention consisted on average of five interventions. Giving orientation and promoting early mobilization were included in every study. Interventions that included giving orientation, promoting early mobilization, and supporting nutrition significantly decreased delirium incidence. Moreover, when health care providers who have an intimate relationship with patients provided non-pharmacological interventions, delirium incidence has significantly decreased.Conclusion: Non-pharmacological intervention, such as giving orientation, promoting early mobilization, should be included to prevent delirium for elderly inpatients. It is important to include healthcare providers who have an intimate relationship or regular contact with patients in order to decrease delirium incidence.

Obesity is characterized by excessive fat accumulation, chronic inflammation, and enhanced oxidative stress that can present a substantial risk for metabolic complications. The aim of this study was to investigate the protective effects of red ginseng (RG), and its bio-transformed form (fermented RG, FRG) by microorganism on obese phenotype, lipid profile, and inflammation and oxidant profiles in rats fed a high-fat (HF) diet. FRG was prepared by fermentation of RG with Lactobacillus pentosus KCCM 12762P. Male Sprague-Dawley rats (n = 8/group; 6 weeks old) were counterbalanced by initial weight into four groups and fed either a low-fat (LF; 10% kcal as fat), high-fat (HF; 45% kcal as fat), or HF diet supplemented with RG or FRG at 1% (w/w) in diet for 6 weeks. General phenotypes (body weight, energy intake, visceral adiposity), lipid and inflammatory profiles, and oxidative states were assessed. RG and FRG supplementation suppressed HF-induced upregulation of proinflammatory cytokine genes, interleukin-6 and tumor necrosis factor alpha, in both white adipose and liver tissues. Similarly, RG and FRG partially reversed HF-induced downregulation of antioxidant enzymes at the gene level. Concomitantly, RG and FRG reduced body weight gain, energy intake, visceral adiposity and the level of serum triglycerides. It is of note that better metabolic profile was observed with FRG than RG for lipid metabolism and inflammation, in the liver in particular. Taken together, we demonstrated that RG and FRG supplementation effectively protected from HF-induced metabolic disturbances by improving obese phenotypes, lipid and inflammatory profiles, and antioxidant defense system.

Aims/Introduction Elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) are well‐established independent risk factors for progression to diabetes, cardiovascular comorbidities and mortality. Most previous studies on the relationships of anthropometric measures with hyperglycemia were carried out among adults and adolescents, but few data are available for the performance predication of the predictors for diagnosing elevated FPG or HbA1c among young children. Materials and Methods Involving 5,556 students of aged 7–9 years, a school‐based cross‐sectional survey was carried out between March and June 2019 in Shenzhen, China. Receiver operating characteristic curve analysis was utilized. Results The median was 4.6 (interquartile range [IQR] 4.3–4.8) mmol/L for FPG and 5.3% (IQR 5.1–5.5%) for HbA1c levels for all participants. For detecting elevated FPG, weight (0.651, IQR 0.583–0.719) and waist circumference (0.650, IQR 0.584–0.717) showed the highest area under the curve and 95% confidence interval, followed by body mass index and the z‐score of body mass index (both 0.635, IQR 0.567–0.703); other anthropometric measures showed poorer diagnostic efficiencies or no ability. For detecting elevated HbA1c, lower efficiencies for the Conicity Index (0.651, IQR 0.583–0.719), waist‐to‐height ratio, waist‐to‐hip ratio and waist‐to‐chest ratio were shown. The correlations of FPG and HbA1c levels with anthropometric indices were weak (Spearman’s r ≤ 0.179). Conclusions None of the evaluated anthropometric indicators approached an adequate predictive accuracy for the detection of elevated FPG or HbA1c levels in Shenzhen children aged 7–9 years. The current study did not recommend anthropometry screening for prediabetes in young children., Few data are available for the performance predication for diagnosing elevated fasting plasma glucose or hemoglobin A1c among young children. A school‐based cross‐sectional survey involving 5,556 students aged 7–9 years was carried out in Shenzhen, China. None of the evaluated anthropometric indicators approached an adequate predictive accuracy for the detection of elevated fasting plasma glucose or hemoglobin A1c levels. The current study did not recommend anthropometry screening for prediabetes in young children.

MicroRNAs (miRNAs) have been reported to serve pivotal roles in the regulation of papillary thyroid cancer (PTC) development; thus, the aim of this study is to identify the impact of miR-203 and AKT3 on the epithelial-mesenchymal transition (EMT), migration and invasion of PTC. MiR-203 and AKT3 expression in PTC tissues and cells were tested. TPC-1 cells and K1 cells were screened for follow-up experiments. Apoptosis-related proteins (Bcl-2 and Bax), EMT-related proteins (Vimentin and E-cadherin), proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) were verified. The effects of upregulated miR-203 and downregulated AKT3 on the biological characteristics of PTC cells in each group were detected via the gain- and loss-of-function assays. The targeting relationship between miR-203 and AKT3 was verified.MiR-203 expression declined and AKT3 heightened in PTC tissues and cells. Upregulated miR-203 and downregulated AKT3 reduced the tumor volume and weight, suppressed cell migration, colony formation, proliferation, invasion, proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) and promoted cell apoptosis, raised E-cadherin and decreased Vimentin protein expression in TPC-1 cells. On the contrary, the K1 cells with the downregulated miR-203 or upregulated AKT3 exhibited an opposite result. This study suggests that upregulated miR-203 suppresses EMT, invasion, proliferation and migration as well as induces apoptosis of PTC cells via downregulated AKT3.

Oxidative stress and hypoxia are two opposite microenvironments involved in HCC metastasis. Thioredoxin (TXN) and hypoxia-inducible factor 2α (HIF-2α) are typical proteins involved in these two different microenvironments, respectively. How these two factors interact to influence the fate on tumor cells remains unknown. Hypoxia facilitated HCC cells withstood oxidative stress and eventually promoted HCC cells metastasis, in which TXN and HIF-2α were mostly involved. Upregulation of TXN/HIF-2α correlated with poor HCC prognosis and promoted HCC metastasis both in vitro and in vivo. Epithelial-mesenchymal transition (EMT) process was involved in TXN/HIF-2α-enhanced invasiveness of HCC cells. Additionally, the stability and activity of HIF-2α were precisely regulated by TXN via SUMOylation and acetylation, which contributed to HCC metastasis. Our data revealed that the redox protein TXN and HIF-2α are both associated with HCC metastasis, and the fine regulation of TXN on HIF-2α contributes essentially during the process of metastasis. Our study provides new insight into the interaction mechanism between hypoxia and oxidative stress and implies potential therapeutic benefits by targeting both TXN and HIF-2α in the treatment of HCC metastasis.

High-throughput genome sequencing and computation have enabled rapid identification of targets for personalized medicine, including cancer vaccines. Synthetic peptides are an established mode of cancer vaccine delivery, but generating the peptides for each patient in a rapid and affordable fashion remains difficult. High-throughput peptide synthesis technology is therefore urgently needed for patient-specific cancer vaccines to succeed in the clinic. Previously, we developed automated flow peptide synthesis technology that greatly accelerates the production of synthetic peptides. Herein, we show that this technology permits the synthesis of high-quality peptides for personalized medicine. Automated flow synthesis produces 30-mer peptides in less than 35 minutes and 15- to 16-mer peptides in less than 20 minutes. The purity of these peptides is comparable with or higher than the purity of peptides produced by other methods. This work illustrates how automated flow synthesis technology can enable customized peptide therapies by accelerating synthesis and increasing purity. We envision that implementing this technology in clinical settings will greatly increase capacity to generate clinical-grade peptides on demand, which is a key step in reaching the full potential of personalized vaccines for the treatment of cancer and other diseases.

Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Background Numerous studies have consistently demonstrated that high body mass index (BMI) is related to elevated serum alanine aminotransferase (ALT) among adults, but little is known about the association regarding adolescents, especially in China. In this study, we aimed to investigate the association between BMI and ALT activity among Chinese adolescents. Methods A school-based cross-sectional study was performed among nine high schools in Shenzhen, China between February 2017 and June 2018. A generalized linear-regression model adjusting for age and gender was conducted, and bivariate correlation analysis between ALT and BMI was also performed. Results A total of 7,271 adolescents aged from 9 years to 17 years were enrolled. Height, weight, BMI, and ALT were higher among boys than among girls (all P Conclusions We found a significant BMI−ALT relationship. BMI at 20.5 kg/m2 may be a cut-off for evaluating serum ALT. BMIs ≥27.1 kg/m2 for boys and ≥24.9 kg/m2 for girls were linked to an elevated ALT activity for Shenzhen adolescents.

BACKGROUND: Use of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We present a systematic approach to estimate “observation windows” (OWs), defined as time periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrate the impact of observation windows on estimating the rates of type 2 diabetes mellitus (diabetes) using EHR diagnosis, medication, and laboratory data from HIV clinical cohorts. METHODS: Data contributed by 16 HIV clinical cohorts to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included: 1) gathering cohort-level data; 2) visualizing and summarizing gaps in observations; 3) systematically establishing start and stop dates during which complete ascertainment of diabetes events was reasonable; and 4) visualizing the diabetes OWs relative to the cohort open and close dates to identify periods of time during which immortal person time was accumulated and events were not fully ascertained. We estimated diabetes occurrence event rates and 95% confidence intervals ([,]) in the most recent decade that data were available (Jan 1, 2007 to Dec 31, 2016). RESULTS: The number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 ([1.29, 1.35] per 100 person-years with the use of diabetes OWs. CONCLUSIONS: As the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete.

Esophageal cancer (EC) is a highly prevalent malignancy in China. According to the data released by National Cancer Registry Center of China in 2015, the prevalence of EC was 21.17/100,000 in China in 2012, ranking fifth among all malignancies; the mortality rate was 15.58/100,000, ranking fourth. It is expected that there will be 477,900 new EC cases nationwide in 2015, whereas 375,000 people will die from EC (1,2). Worldwide, EC is the 8 th most common malignancy, with 416,000 new cases in 2012 (3). At present, EC treatment is based on multidisciplinary treatment, but surgery remains the most effective therapy in optimizing long-term prognosis in patients without metastatic disease. The ideal surgical approach is a matter of debate.

A horizontally polarized (HP) wideband antenna is designed and analyzed for wireless communication in this communication. The HP antenna is a combination of four quarter-wavelength slot elements, and fed by a wideband power divider with equal amplitude and zero phase difference output signals. Equivalent to the current loop, four slot elements rotate around the center of proposed structure, which gives rise to a monopolar radiation pattern. A prototype is designed, fabricated and measured. The results show that a deep null more than 20 dB appears in the broadside of the elevation plane radiation pattern. And a small ripple less than 2 dB in azimuth plane radiation pattern is obtained. The antenna has a wide impedance band of 33.3% for S11

The concept of minimally invasive cardiac surgery has been put forward for more than decades and continued to develop. Recently, minimally invasive aortic valve surgery is established as a safe and effective treatment for various aortic valvular heart diseases and ascending aorta disorders. This study is aimed at analyzing the safety and effectiveness of aortic valve replacement (AVR) through right anterior minithoracotomy for the treatment of patients with low left ventricular ejection fraction (LVEF). Retrospective analyses of 43 cases with low LVEF undergoing AVR through median sternotomy and 43 cases with low LVEF undergoing AVR through right anterior minithoracotomy were performed. Extracorporeal circulation time and aortic cross-clamping time were longer in patients undergoing AVR through right anterior minithoracotomy than those in patients undergoing AVR through median sternotomy ( P < 0.05 ). Patients undergoing AVR through right anterior minithoracotomy exhibited declines in the cardiac surgery intensive care unit (CSICU) stay, duration of mechanical ventilation, and the length of hospital stay than those undergoing AVR through median sternotomy ( P < 0.05 ). The volumes of 24 h chest drainage were reduced in patients undergoing AVR through right anterior minithoracotomy compared with those undergoing AVR through median sternotomy ( P < 0.05 ). The incidence rates of blood transfusion within 24 h and postoperative atrial fibrillation were lower in patients undergoing AVR through right anterior minithoracotomy than those in patients undergoing AVR through median sternotomy ( P < 0.05 ). As for cardiac function, patients with right anterior minithoracotomy had decreased left ventricular end diastolic diameter (LVEDD) but increased LVEF and left ventricular fractional shortening (LVFS) when compared to median sternotomy ( P < 0.05 ). With regard to inflammatory response, the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in patients with right anterior minithoracotomy were much lower than those in median sternotomy ( P < 0.05 ). All these results indicate that right anterior minithoracotomy is an alternative, less invasive approach to median sternotomy during AVR for patients with low LVEF.

Background People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods We studied 102 777 PLWH during 1996–2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for Conclusions Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

OBJECTIVES Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the incidence of VTE after major thoracic surgery ranges from 2.3% to 15%. However, there have been no such data from China so far. To evaluate the incidence of postoperative VTE, we conducted a single-centre, prospective cohort study. METHODS Patients who underwent lung resections between July 2016 and March 2017 were enrolled in this study. None of the patients received any prophylaxis perioperatively. All patients were screened for deep venous thrombosis (DVT) using non-invasive duplex lower-extremity ultrasonography 30 days before surgery and within 30 days after surgery and before discharge. Chest tomography, pulmonary embolism protocol was carried out if patients had one of the following conditions: (i) typical symptoms of pulmonary embolism, (ii) high Caprini score (≥9 points) and (iii) newly diagnosed postoperative DVT. RESULTS Two hundred and sixty-two patients undergoing lung surgery were enrolled, including 115 benign and 147 malignant disease cases. The procedures included 84 sublobar lung resections, 161 lobectomies, 5 pneumonectomies and 12 mixed procedures. The overall postoperative incidence of VTE was 11.5% (30 of 262). Twenty-four patients were diagnosed with DVT (80.0%) and 6 with DVT + pulmonary embolism (20.0%). None of the patients diagnosed with VTE had obvious symptoms of VTE. The median time for VTE detection was 5 days postoperatively. The incidence of VTE was 7.0% in patients with benign lung diseases and 15.0% in those with malignant lung diseases (P

We aimed to explore whether there were cold and heat temperature adverse effects on years of life lost (YLL) for non-accidental mortality in Yuxi, a southwest plateau region of China. From data for 89,467 non-accidental deaths over an 8-year study period, we used a general linear regression model combined with a distributed lag non-linear model to assess the burden of disease non-accidental mortality due to ambient temperature with the YLL indicator. We estimated the mean YLL change per 1 °C decrease from the 25th to 1st percentile mean temperature as the cold effect and per 1 °C increase from the 75th to 99th percentile as the heat effect. The 95% empirical confidence intervals (eCIs) were calculated by using a bootstrap simulation method. The exposure–response curve between average temperature and YLL was U-shaped. The cold effect peaked at the first day after exposure and disappeared at 2 weeks, and the heat effect only lasted for the first 3 days. A per 1 °C decrease from the 25th to 1st mean temperature percentile was associated with an increase of 15.6 (95% eCI: 2.4, 22.9) in YLL for non-accidental diseases, and the cumulative effects due to cold were stronger in contrast to that attributed by heat. Cold temperature had a significant impact on YLL among the subgroups, with higher YLL in cardiovascular disease, stroke, males, Han nationality, married, and those engaged in agriculture than their corresponding categories. An increasing death burden of non-accidental in Yuxi of China due to cold temperature was demonstrated, and the association was also modified by specific disease causes and individual features.

There are complex relationships among individual, family, community, and social factors related to breastfeeding. Immigrant mothers, specifically, face several unique challenges to practicing breastfeeding while negotiating these factors within two cultural worlds. Grounded in the theory of planned behavior and the ecological perspective, our qualitative study findings unveil a part of the complex and dynamic process of breastfeeding decision-making among Korean immigrant mothers in the United States. To elicit mothers’ underlying beliefs of attitude and intention toward breastfeeding as immigrants, we conducted in-person interviews with 13 pregnant and postpartum Korean immigrant mothers, ages ranging from 30 to 39. The findings revealed that Korean mothers held positive attitudes toward breastfeeding. However, translation of these positive attitudes toward breastfeeding into actual practice depended on the feasibility of actual breastfeeding by mothers. To overcome several barriers to breastfeeding, such as inadequate milk supply, health concerns, employment status, and the relationship with a firstborn child, many Korean mothers combined breastfeeding with formula feeding. The factors that shaped the development of beliefs and behavioral intentions toward breastfeeding among Korean immigrant mothers included the dynamic family interactions with their children, husbands, mothers, mothers-in-law, and sisters; support from friends and infant care experts; information available through various technology and media; and Korean-specific cultural traditions. Our findings suggest possible directions for future cross-cultural research on breastfeeding within diverse family contexts, and may inform the design of population specific intervention programs.

Background The bone morphologies of intact knees were measured and compared between Chinese and Caucasian populations. However, to assess if distinct designs of implants are necessary for the Chinese population owing to different morphologies and sizes, the knee measurements after osteotomy performed in total knee arthroplasty were evaluated. Methods Thirty-seven Caucasian and 50 Chinese patients' knees were examined using computed tomography scans. Mimics were applied to reconstruct 3-dimensional bone models. Dimensions of the 3-dimensional knee models and simulated bone resections during total knee arthroplasty were measured using Geomagic Studio and Pro/ENGINEER. The morphologic measurements of the native and resected femur and tibia included the anteroposterior (AP) depth, mediolateral (ML) width, notch width, knee physical valgus angle, tibial slope angle, and the ML-to-AP ratio of the femur, tibia, and resected femur. Statistical analysis was performed using the independent samples t test and the Pearson correlation coefficient in SPSS for Windows. Values of P < .05 were considered significant. Results No measurements were significantly different between the Chinese and Caucasian knees. However, the Chinese female showed significant differences compared with the Chinese male on distal femoral measurements both presimulated and postsimulated osteotomy such as a smaller mean ML-to-AP ratio in presimulated (1.3 ± 0.1) and postsimulated (1.3 ± 0.1) osteotomy. Conclusion The necessity of designing a full set of total knee components specifically for the Chinese population is still undetermined. However, we suggest designing femoral components specific for the Chinese females because of different postosteotomy distal femoral ML-to-AP ratio between the Chinese males and the Chinese females.

Background: The aim of this study was to investigate the diagnostic value of the intravoxel incoherent motion (IVIM) for distinguishing non-metastatic from metastatic mediastinal lymph nodes in lung cancer. Methods: IVIM-diffusion weighted imaging (DWI) exams were performed preoperatively on 66 patients with lung cancer from October 2015 to June 2016 in Beijing Chao-Yang Hospital, Capital Medical University. Fifty patients underwent enhanced chest computed tomography (CT) in our hospital, while the other 16 patients already had enhanced chest CT images when they were admitted. The patients’ complete preoperative examination included chest magnetic resonance imaging (MRI), enhanced chest CT, head MRI, bone scanning and cardiopulmonary function testing. None of the patients were receiving any treatment for their cancer prior to their evaluation and surgery, including neoadjuvant chemotherapy, radiation therapy, immunotherapy or gene targeted therapy. The following IVIM parameters of the mediastinal lymph nodes were measured: the short axis diameter, apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). All of the patients underwent lobectomy and lymph node dissection. We compared the CT and MRI results and analysed the IVIM parameters of the pathologically determined non-metastatic and metastatic mediastinal lymph nodes in our 50 patients to generate the ROC curves and determine the best cut-off value for diagnosis. The remaining 16 patients’ IVIM parameters were used to verify the diagnostic cut-off value. This study was approved by the institutional research ethics committee of Beijing Chao-Yang Hospital (2014-S-166), and all the patients signed the MRI informed consent. Results: In this study, MRI was used to measure 140 groups of mediastinal lymph nodes in 50 cases, and the results showed that 19 groups of mediastinal lymph nodes were metastatic, while 121 groups of mediastinal lymph nodes were non-metastatic. The pathological analysis showed that 20 groups of mediastinal lymph nodes were metastatic and 120 groups of mediastinal lymph nodes were non-metastatic. CT was used to measure 273 groups of mediastinal lymph nodes, and the result showed that 34 groups of mediastinal lymph nodes were metastatic, while 239 groups of mediastinal lymph nodes were non-metastatic. The pathological analysis showed that 20 groups of mediastinal lymph nodes were metastatic and 253 groups of mediastinal lymph nodes were non-metastatic. The ADC, D, D*, f values and the short axis diameters of the non-metastatic lymph nodes (n=121) were 2.9370±0.743×10 −3 , 0.533±0.175×10 −3 , 0.384±0.121×10 −3 mm 2 /s, 0.426±0.120, 6.903±1.831 mm, respectively, and 1.863±0.691×10 −3 , 0.454±0.204×10 −3 , 0.358±0.106×10 −3 mm 2 /s, 0.413±0.085, 7.705±2.213 mm, respectively, for the metastatic lymph nodes (n=19). The ADC and D values of the non-metastatic lymph nodes were significantly higher than the values for the metastatic lymph nodes (P −3 mm 2 /s (0.897, 93.3%, 80.0%), Youden index 0.733; and D =0.344×10 −3 mm 2 /s (0.651, 90.8%, 50.0%), Youden index 0.651. When these cut-off values were applied as the diagnostic criteria in the remaining cases and compared with the pathology results, the diagnostic performance was good. Conclusions: IVIM is useful to distinguish metastatic from non-metastatic lymph nodes in lung cancer. The ADC and the D values are significantly lower in metastatic lymph nodes, making these parameters more sensitive than the other parameters (D*, f, and short axis diameter). As a result, IVIM can be used in the N-stage diagnosis of lung cancer.

Artificial intelligence (AI) based on deep learning, convolutional neural networks and big data has been increasingly effective in the diagnosis and treatment of multiple primary pulmonary nodules. In comparison to previous imaging systems, AI measures more objective parameters such as three‐dimensional (3D) volume, probability of malignant nodules, and possible pathological patterns, making the access to the properties of nodules more objective. In our retrospective study, a total of 53 patients with synchronous and metachronous multiple pulmonary nodules were enrolled of which 33 patients were confirmed by pathological tests to have primary binodules, and nine to have primary trinodules. A total of 15 patients had only one focus removed. The statistical results showed that the agreement in the AI diagnosis and postoperative pathological tests was 88.8% in identifying benign or malignant lesions. In addition, the probability of malignancy of benign lesions, preinvasive lesions (AAH, AIS) and invasive lesions (MIA, IA) was totally different (49.40±38.41% vs 80.22±13.55% vs 88.17±17.31%). The purpose of our study was to provide references for the future application of AI in the diagnosis and follow‐up of multiple pulmonary nodules. AI may represent a relevant diagnostic aid that shows more accurate and objective results in the diagnosis of multiple pulmonary nodules, reducing the time required for interpretation of results by directly displaying visual information to doctors and patients and together with the clinical conditions of MPLC patients, offering plans for follow‐up and treatment that may be more beneficial and reasonable for patients. Despite the great application potential in pneumosurgery, further research is needed to verify the accuracy and range of the application of AI.

Background: To compare the outcome of transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in low and intermediate risk patients with severe aortic stenosis (AS). Randomized controlled trials (RCT) and propensity score matching (PSM) studies compare TAVR with SAVR in patients at low and intermediate surgical risk. Methods: Two authors searched relevant literature independently, then extracted data from the included studies, and assessed risk of bias and quality of study separately according to different study designs, besides that, the extracted data was analyzed via utilization of GRADE system to evaluate the quality of evidence separately. Results: Overall 15 studies (5 RCTs, 10 PSM studies) with total 12,057 patients were selected. Mortality and disabling stroke during follow-up period were comparable between TAVR and SAVR (RR 1.09, 95% CI: 0.81 to 1.46; RR 0.7, 95% CI: 0.45 to 1.07, respectively), TAVR revealed to be superior to SAVR regarding acute kidney injury (AKI), and onset of new atrial fibrillation (AF) (RCT: high certainty; AKI in PSM: moderate certainty, AF in PSM: low certainty). These results of RCT and PSM studies are consistent. In RCT review, SAVR was better in the following aspects: aortic valve (AV) re-intervention (high certainty), vascular complications, pacemaker implantation (moderate certainty), but comparable in the following aspects: myocardial infarction (MI), aortic insufficient (AI) (moderate certainty), major bleeding (low certainty). In PSM review, SAVR revealed a better result in AI and vascular complications (high certainty), but in the aspects of AV re-intervention, pacemaker implantation, major bleeding and MI (low certainty), it was comparable. Conclusions: TAVR is comparable to SAVR in terms of mortality and disabling stroke in severe AS patients at low and intermediate risk, but higher proportion of AV re-intervention observed in TAVR. Those results should encourage caution when extending the indications of TAVR into low risk patients, especially for young low risk patients. Systematic review registration: PROSPERO CRD 42018112626.

BackgroundResearch is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.MethodsWe studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FindingsOf 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months

Background Breakfast is commonly described as the most important meal of the day; however, we have little information regarding its relevance for childhood overweight and obesity in southern mainland China. This study aimed to assess the association between breakfast preferences, consumption location and overweight and obesity for children in Shenzhen. Methods Among 6126 children (median age 7.2 years) at primary schools, 3504 were finally included after a questionnaire survey and physical examination. Ten commonly consumed foods/beverages for breakfast in southern China were exposure variables, and consumption location, total energy demographic and other dietary characteristics were covariates in logistic regression to determine the effect of breakfast preferences on overweight and obesity, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results Probability of overweight/general obesity was inversely associated with children eating plain congee for breakfast (adjusted OR 0.689, 95% CI 0.566–0.838), restricted to boys after stratification. Probability of overweight/general obesity and central obesity was positively associated with usually eating steamed rice roll for breakfast (OR 1.309, 95% CI 1.090–1.571 and OR 1.351, 95% CI 1.064–1.717, respectively), but the effect on overweight/obesity remained statistically significant for only boys after stratification. Eating steamed rice roll for breakfast and eating out for breakfast had an additive interaction on overweight/obesity. Additionally, eating bread for breakfast had a mild favorable effect on overweight/obesity but only for girls. Conclusions Keeping a healthy weight might benefit children who eat plain congee or bread for breakfast in China. However, frequent consumption of steamed rice roll for breakfast and especially eating out could contribute to overweight and obesity. Thus, we need to promote a healthier breakfast pattern among children in southern China to reduce the odds of obesity.

Reprogrammed energy metabolism is an emerging hallmark of cancer. Lactate dehydrogenase A (LDHA), a key enzyme involved in anaerobic glycolysis, is frequently deregulated in human malignancies. However, limited knowledge is known about its roles in the progression of osteosarcoma (OS). In this study, we found that LDHA is commonly upregulated in four OS cell lines compared with the normal osteoblast cells (hFOB1.19). Treatment with FX11, a specific inhibitor of LDHA, significantly reduced LDHA activity, and inhibited cell proliferation and invasive potential in a dose dependent manner. Genetic silencing of LDHA resulted in a decreased lactate level in the culture medium, reduced cell viability and decreased cell invasion ability. Meanwhile, silencing of LDHA also compromised tumorigenesis in vivo. Furthermore, knockdown of LDHA remarkably reduced extracellular acidification rate (ECAR) as well as glucose consumption. In the presence of 2-DG, a glycolysis inhibitor, LDHA-mediated cell proliferation and invasion were completely blocked, indicating the oncogenic activities of LDHA may dependent on Warburg effect. Finally, pharmacological inhibition of c-Myc or HIF1α significantly attenuated LDHA expression. Taken together, upregulated LDHA facilitates tumor progression of OS and might be a potential target for OS treatment.

We previously found that a low dose of sorafenib had a prometastatic effect on hepatocellular carcinoma (HCC), which was caused by downregulation of TIP30 expression. More recently, metformin has been shown to have potential as a preventive and therapeutic agent for different cancers, including HCC. This study evaluated whether the combination of sorafenib and metformin is sufficient to revert the expression of TIP30, thereby simultaneously reducing lung metastasis and improving survival. Our data show that the combination of sorafenib and metformin inhibits proliferation and invasion in vitro, prolongs median survival, and reduces lung metastasis of HCC in vivo. This effect is closely associated with the upregulation of TIP30, partly through activating AMP-activated protein kinase. Thioredoxin, a prometastasis factor, is negatively regulated by TIP30 and plays an essential role during the process of HCC metastasis. Overall, our results suggest that metformin might be a potent enhancer for the treatment of HCC by using sorafenib.

Background: The high incidence of venous thromboembolism (VTE) has been perceived in post thoracic surgery patients. However, the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for VTE predicting is not clear. To investigate that, we conducted a prospective single center study. Methods: A total of 111 patients undergoing lung surgery were enrolled in this study, included 52 primary lung cancer patients and 59 benign lung disease patients from July 2016 to March 2017. Preoperative and postoperative days 1, 3, and 5 coagulation and fibrinolysis related parameters were tested, including antithrombin (AT), fibrinogen degradation product (FDP), prothrombin time (PT), prothrombin time activity (PA), prothrombin time ratio (PR), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (FBG), thrombin time (TT) and D-Dimer. The Doppler ultrasonography was performed before and after surgery for deep venous thrombosis (DVT) confirmation. Patients with new postoperative DVT, unexplained dyspnea, hemoptysis, chest pain, or high Caprini score (≥9) were received further computer tomography pulmonary angiography (CTPA) for pulmonary embolism (PE). We used the area under receiver-operating-characteristic (ROC) curve to discriminate patients between those who developed VTE and those who did not. Single factor analysis was utilized to define risk factors associated with VTE. Results: The overall incidence of VTE was 16.2% (18/111). The incidence of VTE in primary lung cancer patients was 23.1% (12/52), much higher than that in benign lung diseases 10.2% (6/59), but did not reach statistical significance (P=0.066). Among 18 VTE patients, 83.3% was DVT, 16.7% was DVT + PE and 72.2% was muscular veins of the calf thrombosis. D-Dimer was much higher in VTE group than that in non-VTE group preoperatively and at postoperative days 1, 3 (0.64±0.24 vs . 0.33±0.06, P=0.007; 3.14±0.75 vs . 1.51±0.09, P=0.005, and 1.88±0.53 vs . 0.76±0.05, P=0.001, respectively). And the ROC curve areas of preoperative and postoperative days 1, 3 of D-Dimer were 0.70, 0.71 and 0.74, respectively. And FDP was much higher in VTE group than that in non-VTE group at postoperative day 3 (6.78±1.43 vs . 3.79±0.15, P=0.004). But AT, PT, PA, PR, INR, APTT, FBG and TT there were no significantly difference. Conclusions: The overall incidence of VTE after lung surgery was 16.2%. The patients with preoperative high D-Dimer should receive VTE prophylaxis.

Esophageal cancer is an aggressive malignancy and a major cause of cancer-related deaths globally. In 2012, about 460,000 new cases of esophageal cancer were diagnosed worldwide, with 400,000 deaths attributed to the disease (1).

Background High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. Methods Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. Results We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Conclusions Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.

Thoracic aortic aneurysm and dissection (TAAD) is due to degeneration of the aorta and causes a high mortality rate, while molecular mechanisms for the development of TAAD are still not completely understood. In the present study, 3-aminopropionitrile (BAPN) treatment was used to induce TAAD mouse model. Through transcriptome analysis, we found the expression levels of genes associated with interleukin-3 (IL-3) signaling pathway were up-regulated during TAAD development in mouse, which were validated by real-time PCR. IL-3 positive cells were increased in TAAD mouse aortas, especially for smooth muscle cells (SMCs). IL-3 deficiency reduced BAPN-induced TAAD formation. We then examined the matrix metalloproteinases (MMPs) expression during TAAD formation in both wild-type and IL-3 deficient mice, showing that MMP12 were significantly down-regulated in IL-3 deficient aortas. Mechanistically, we found recombinant IL-3 could increase MMP12 production and activity from macrophages in vitro. Silencing of IL-3 receptor β, which was mainly expressed in macrophages but not SMCs, diminished the activation of c-Jun N terminal kinase (JNK)/extracellular-regulated protein kinases 1/2 (ERK1/2)/AP-1 signals, and decreased MMP12 expression in IL-3 stimulated macrophages. Moreover, both circulating and aortic inflammation were decreased in IL-3 deficient aortas. Taken together, our results demonstrated that IL-3 stimulated the production of MMP12 from macrophages by a JNK- and ERK1/2-dependent AP-1 pathway, contributing to TAAD formation. Thus, the IL-3/IL-3Rβ/MMP12 signals activation may be an important pathological mechanism for progression of TAAD.

Overexpression of CUB domain-containing protein 1 (CDCP1), a transmembrane glycoprotein and major substrate of Src family kinases (SFKs), always indicates unfavorable outcomes in various cancers. The characteristics of CDCP1 in hepatocellular carcinoma (HCC) have not been assessed. Most recently, CDCP1 was identified as a specific target gene of HIF-2α in clear cell renal carcinoma (CC-RCC). However, considering the role of HIF-2α in the progression of HCC is highly controversial, it is necessary to figure out whether HIF-2α and CDCP1 play a significant part in the metastasis of HCC. Our results showed that HIF-2α and CDCP1 were both induced by hypoxia, and the activation of CDCP1 was HIF-2α dependent. CDCP1 was governed by HIF-2α at mRNA and protein levels in HCC cell lines. Moreover, knocking down of HIF-2α not only inhibited cell invasion but also impaired the expression of Tyr(311) phosphorylation of protein kinase Cδ (PKCδ) which is a downstream factor of CDCP1 and has been reported to induce malignant migration in various tumors. Analysis of human HCC samples showed a negative correlation of CDCP1 expression with disease-free survival, and CDCP1 was an independent prognostic factors of disease-free survival. Taken together, these data demonstrated that HIF-2α could promote HCC cell migration by regulating CDCP1, and targeting HIF-2α-CDCP1-PKCδ pathway might be effective to inhibit HCC metastasis.

Background Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. Methods We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. Results There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts

Background Unroofed coronary sinus syndrome (URCSS) is a spectrum of cardiac anomalies in which part (partial type) or the entire common wall (complete type) between the coronary sinus (CS) and left atrium is absent. It is commonly associated with a persistent left superior vena cava (PLSVC). The PLSVC can even anomalously connect to the left atrium in complete type anomaly. URCSS has been reported to be associated with delayed diagnosis and life-threatening cerebral injury. The purpose of the present study was to review our experience with surgical correction of this often-concealed malformation and discuss methods for reducing diagnostic omission. Methods Thirty-six patients with URCSS who underwent surgical treatment from 1998 to 2015 in our institution were enrolled in this retrospective analysis. Results The mean age of the patients was 21.8 ± 20.9 years. Type I anomalies were found in 15 (41.7%) patients, type II in 4 (11.1%), type III in 6 (16.7%), and type IV in 11 (30.6%). A patient presenting with URCSS without other defects was identified in six (16.7%). One patient (2.8%) had a history of paradoxical embolisation. Twenty-five patients (69.4%) were diagnosed before surgery. Ten patients (27.8%) were diagnosed with URCSS intraoperatively. One patient (2.8%) was diagnosed with URCSS by follow-up echocardiography after device occlusion for atrial septal defect. Coronary sinus ostium dilation was the most important clue leading to partial type lesion disclosure intraoperatively. The anomalous PLSVC of 15 patients was repaired using roof tunnel technique in four (26.7%) cases, baffle redirection in eight (53.3%) cases, posterior left atrial wall plicating in two (13.3%) cases, and extracardiac bypass in one (6.7%) case. Postoperative complete atrioventricular block occurred in one patient (2.8%). One patient died postoperatively (2.8%). All patients are doing well after discharge from hospital. Conclusions Diagnostic suspicion can contribute to lesion disclosure. Surgical correction has good long-term outcomes and low risks.

Background: To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Methods: Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Results: Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. Conclusions: It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.

Background Sorafenib is recognized as a standard treatment for advanced hepatocellular carcinoma (HCC). However, many patients have to adopt dose reduction or terminate the use of sorafenib because of side effects. In addition, a large number of patients are resistant to sorafenib. Thus, it is essential to investigate the underlying mechanisms of the resistance to sorafenib and seek potential strategy to enhance its efficacy. Methods The protein expression of hypoxia-inducible factors (HIF)-2α, 30-kDa HIV Tat-interacting protein (TIP30), E-cadherin, N-cadherin, and pAMPK was detected by Western blot. Cell viability assays were performed to study the influence of metformin and sorafenib on cell proliferation. Annexin V-FITC apoptosis assays were used to detect the influence of metformin and sorafenib on cell apoptosis. The relationship between HIF-2α and TIP30 was studied using gene silencing approach and chromatin immunoprecipitation assay. To investigate the effect of metformin and sorafenib on postoperative recurrence and lung metastasis of HCC in tumor-bearing mice, the mice were orally treated either with metformin or sorafenib once a day for continuous 37 days after the operation to remove the lobe where the tumor was implanted. CD31, Ki67, and TUNEL were examined by immunohistochemistry. Results Our study demonstrated that metformin synergized with sorafenib reduced HIF-2α expression as examined by Western blot. Gene silencing approach indicated TIP30 was upregulated after knocking-down of HIF-2α and chromatin immunoprecipitation assay revealed that HIF-2α could bind to TIP30 promoter under hypoxic condition. Cell Counting Kit-8 (CCK8) cell viability assay and Annexin V-FITC apoptosis assay showed that metformin in combination with sorafenib suppressed cell proliferation and promoted cell apoptosis. Besides, combined therapy suppressed epithelial-mesenchymal transition (EMT) process both in vitro and in vivo. Moreover, metformin in combination with sorafenib significantly minimized postoperative recurrence and lung metastasis of HCC in orthotopic mouse model. Combined therapy inhibited CD31 and Ki67 expression but promoted TUNEL expression. Conclusions Metformin may potentially enhance the effect of sorafenib to inhibit HCC recurrence and metastasis after liver resection by regulating the expression of HIF-2α and TIP30. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0253-6) contains supplementary material, which is available to authorized users.

Pulmonary carcinoma is uncommon after lung transplant, but doubtlessly affects recipient survival independently of other complications. Small cell lung cancer is much rarer after transplant than non-small cell lung cancer. We report a case of mediastinal small cell lung carcinoma confirmed by endobronchial ultrasound biopsy that occurred 18 months after a single lung transplant for interstitial pulmonary fibrosis in a 58-year-old male non-smoker. The patient died shortly after of distant metastasis. Our report confirms the usefulness of tumor markers and positron-emission tomography-computed tomography as routine tests for earlier detection of malignant disease after lung transplant.

The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK.

Objective It is known that T lymphocytes are activated in human abdominal aortic aneurysms (AAAs). γδT cells, as a subset of T cells, play a role in many inflammation-related diseases. However, whether γδT cells participate in the formation of AAA remains unknown. In this study, we explored the role of γδT cells in AAA lesions. Methods and Results Using the porcine pancreatic elastase-induced AAA model, we found that knock out of γδT cells significantly attenuated AAA formation. To elucidate how γδT cells contribute to AAA, microarray analysis was performed, which found that the phosphoinositide 3-kinase/AKT signaling pathway was activated in elastase-perfused γδT knockout (γδT KO) mice. By studying differentially expressed genes involved in phosphoinositide 3-kinase signaling, we found that proliferation-related genes ( Sos1, Mtor, Myc ) were upregulated whereas apoptosis-related genes ( Pten, Bcl1, Bad ) were downregulated in elastase-perfused γδT KO mice. Furthermore, histopathologic analysis showed increased PCNA + and decreased TUNEL + cells in elastase-perfused γδT KO mice compared with wild-type mice. In addition, inflammatory cytokines including interleukin-1β, Mcp-1, and tumor necrosis factor-α were downregulated in the aneurysm tissues of elastase-perfused γδT KO mice. Conclusions These data reveal a pathogenic role of γδT cells in the experimental AAA model, likely through mechanisms regulating cell proliferation and mediating inflammatory response. Thus, targeting of γδT cells may offer a potential therapeutic method for aortic aneurysms.

Yes-associated protein (YAP) is a main mediator of the Hippo pathway, which promotes cancer development. Here we show that YAP promotes resistance to erlotinib in human non-small cell lung cancer (NSCLC) cells. We found that forced YAP overexpression through YAP plasmid transfection promotes erlotinib resistance in HCC827 (exon 19 deletion) cells. In YAP plasmid-transfected HCC827 cells, GTIIC reporter activity and Hippo downstream gene expression of AREG and CTGF increased significantly (P

Background The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation. Methods Protein and mRNA levels of CK2α and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines. Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay. Results In this study, we show that CK2α is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2α and Gli1 were broadly elevated and correlated (n = 52, r = 0.401, P