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The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated NSCLC patients. Among 190 bone metastasis patients, 61 had initial SREs and 73 received denosumab. We analyzed patient characteristics, SRE-free survival (SRE-FS), and overall survival (OS). In metastatic EGFR-mutated NSCLC, bone metastasis was associated with a poorer OS (21.7 vs. 33.0 months; p < 0.001). Bone metastasis patients with initial SREs at diagnosis had an even shorter OS, compared with those without initial SRE (15.4 vs. 23.6 months; p = 0.026). Denosumab reduced SRE incidence (hazard ratio (HR) 0.57 (95% confidence interval (CI) 0.34−0.94; p = 0.027) and was associated with improved OS (26.6 vs. 20.1 months; p = 0.015). A multivariate analysis demonstrated that denosumab treatment was correlated with a lower incidence of SRE (HR 0.61 (95% CI 0.37−0.98); p = 0.042) and better OS (HR 0.60 (95% CI 0.41−0.88); p = 0.008). In subgroup analyses, denosumab prolonged SRE-FS (HR 0.36 (95% CI 0.19−0.79); p = 0.009) in patients without initial SREs and was related to a better OS (25.3 vs. 12.9 months; p = 0.016) in patients with initial or pre-existing SREs. Osteonecrosis of the jaw was diagnosed in two patients (2.74%) receiving denosumab. Our study confirmed the association between initial SREs and a worse outcome and provided novel evidence of the survival benefit of denosumab for EGFR-mutated NSCLC patients with bone metastasis.

Photodetectors are widely applied in modern industrial fields because they convert light energy into electrical signals. We propose a printable silver (Ag) paste electrode for a highly flexible metal-semiconductor-metal (MSM) broadband visible light photodetector as a wearable and portable device. Single-crystal and surface-textured silicon substrates with thicknesses of 37.21 μm were fabricated using a wet etching process. Surface texturization on flexible Si substrates enhances the light-trapping effect and minimizes reflectance from the incident light, and the average reflectance is reduced by 16.3% with pyramid-like structures. In this study, semitransparent, conductive Ag paste electrodes were manufactured using a screen-printing with liquid-phase process to form a flexible MSM broadband visible light photodetector. The transmittance of the homemade Ag paste solution fell between 34.83% and 36.98% in the wavelength range of visible light, from 400 nm to 800 nm. The highest visible light photosensitivity was 1.75 × 10 4 at 19.5 W/m 2 . The photocurrents of the flexible MSM broadband visible light photodetector were slightly changed under concave and convex conditions, displaying stable and durable bending properties.

Background: Through the systematic large-scale profiling of metabolites, metabolomics provides a tool for biomarker discovery and improving disease monitoring, diagnosis, prognosis, and treatment response, as well as for delineating disease mechanisms and etiology. As a downstream product of the genome and epigenome, transcriptome, and proteome activity, the metabolome can be considered as being the most proximal correlate to the phenotype. Integration of metabolomics data with other -omics data in multi-omics analyses has the potential to advance understanding of human disease development and treatment., Aim of Review: To understand the current funding and potential research opportunities for when metabolomics is used in human multi-omics studies, we cross-sectionally evaluated National Institutes of Health (NIH)-funded grants to examine the use of metabolomics data when collected with at least one other -omics data type. First, we aimed to determine what types of multi-omics studies included metabolomics data collection. Then, we looked at those multi-omics studies to examine how often grants employed an integrative analysis approach using metabolomics data., Key Scientific Concepts of Review: We observed that the majority of NIH-funded multi-omics studies that include metabolomics data performed integration, but to a limited extent, with integration primarily incorporating only one other -omics data type. Some opportunities to improve data integration may include increasing confidence in metabolite identification, as well as addressing variability between -omics approach requirements and -omics data incompatibility., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs., Methods: CD34 + fibrocytes were purified from peripheral blood of asthmatic (Global Initiative for Asthma treatment step 4-5) and normal subjects and cultured for 5∼7 days. In a transwell plate, ASMCs were co-cultured with fibrocytes at a ratio of 2:1, ASMCs were cultured alone (control condition), and fibrocytes were cultured alone for 48 h. Measurements were obtained of interleukin-8 (IL-8), IL-6, IL-17, thymic stromal lymphopoietin, and IL-33 levels in the supernatant and IL-33 levels in the cell lysate of the co-culture. Screening for intracellular signaling in the ASMCs after stimulation was performed using condition medium from the patients' co-culture (PtCM) or IL-8. mRNA and western blot analysis were used to analyze AKT/mTOR signaling in ASMCs stimulated via treatment with PtCM or IL-8., Results: Compared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs., Conclusion: The interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Chang, Lo, Lo, Yu, Lin, Kuo and Lin.)

Objective: To evaluate the association of thromboytopenia with mortality of Standford type A aortic dissection after cardiopulmonary bypass surgery. Methods: Total of 498 patients with Standford type A aortic dissection after surgery in Fuwai Hospital of the Chinese Academy of Medical Sciences from May 2017 to December 2018 were collected retrospectively. There were 350 males and 148 females, with a mean age of (51.7±12.0) years. The patients were divided into thrombocytopenia group (platelet count<75×10 15 /L, n =178) and normal platelet group (platelet count≥75×10 15 /L, n =320) according to the lowest platelet count within 72 hours after surgery. The perioperative in-hospital mortality and related complications were calculated by univariate and multivariate logistic regression analysis. The primary endpoint was in-hospital mortality, and the secondary endpoints included secondary thoracotomy, pneumonia, postoperative continuous renal replacement therapy, paraplegia, heart failure, length of hospital stay and intensive care unit (ICU) stay time. Results: The morbidity of thrombocytopenia after Standford type A aortic dissection surgery was 35.7% (178/498). Univariate logistic regression analysis showed that postoperative thrombocytopenia was significantly associated with in-hospital mortality and 7 secondary endpoints ( P <0.05). Multivariate logistic regression analysis showed thrombocytopenia after aortic dissection surgery was significantly associated with increased postoperative mortality ( OR =12.57, 95% CI : 2.26-69.93, P =0.004), secondary thoracotomy ( OR =6.21, 95% CI : 1.31-29.46, P =0.022), continuous renal replacement therapy ( OR =7.51, 95% CI : 2.53-22.34, P <0.001), paraplegia ( OR =23.99, 95% CI : 1.47-392.21, P =0.026), heart failure ( OR =4.71, 95% CI : 1.19-18.62, P =0.027) and longer ICU stay time ( OR =1.86, 95% CI : 1.11-3.12, P =0.019). Conclusions: Thrombocytopenia after Standford type A aortic dissection after cardiopulmonary bypass surgery (the lowest platelet count within 72 hours) is strongly associated with postoperative in-hospital mortality. Trying to avoid the factors related to thrombocytopenia can prevent more complications at the same time.

Background: Continuous renal replacement therapy (CRRT) is a common medical treatment for critically ill patients. The alarm management component of CRRT is urgent and time sensitive. Patient safety and survival rates are jeopardized if critical care nurses do not handle this situation properly. However, clinical settings cannot provide nurses with the opportunity to practice alarm management, which results in related training difficulties. Based on a survey conducted in May 2018, the rate of proper alarm management for the nurses in our CRRT unit was only 53.1%. An investigation attributed this low rate to inadequacies in standard procedures, resources for reference, opportunities for hands-on experience, professional training at different levels, immediate assistance from industry, and lack of familiarity with the purpose and handling of alarm incidents. These findings motivated our project team to improve alarm management., Purpose: To increase the accuracy of alarm management in CRRT critical care nurses to more than 90%., Resolutions: This project, which was implemented from September 8th, 2018 to August 31st, 2019, adopted a diverse and effective teaching strategy that included establishing standard procedures and technical tests; creating a plan for a case scenario simulation course using flipped teaching; providing scenario simulation videos; and designing online scenario simulation interactive exercises, nursing manuals, and flashcards of simplified procedures., Results: The accuracy rate of proper alarm management for CCRT critical care nurses increased from 53.1% to 98.9%., Conclusions: Diverse teaching strategies may be used to effectively enhance the care provided by critical care nurses, increase patient safety, and improve the quality of care. The findings and strategies in this study may also be applied to other intensive care units.

Objective: To examine the early outcome of valve sparing aortic root replacement with reimplantation technique (David procedure) with partial upper sternotomy. Methods: From April 2016 to April 2020, 31 patients underwent valve sparing aortic root replacement under partial upper sternotomy at Vascular Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. There were 28 males and 3 females, aging (44±13) years (range: 11 to 65 years). Preoperative aortic regurgitation was found greater than moderate in 15 patients, moderate in 6 patients and less than moderate in 10 patients. The diameter of aortic annulus was (26±3) mm (range: 21 to 34 mm), the diameter of aortic sinus was (51±6) mm (range: 41 to 68 mm), the diameter of ascending aorta was (43±8) mm (range: 26 to 62 mm). The preoperative ejection fraction was (65±4) % (range: 59% to 72%) and left ventricular end-diastolic diameter was (55±6) mm (range: 42 to 68 mm). All cases were treated with David Ⅰ procedure, including simple David procedure in 26 patients, David+ascending aorta and partial aortic arch replacement in 3 patients, David+thoracic endovascular aortic repair in 1 patient, David+stent elephant trunk implantation in 1 patient. Results: The operation time, cardiopulmonary bypass time and aortic cross-clamping time were (330±58) minutes (range: 214 to 481 minutes), (138±23) minutes (range: 106 to 192 minutes) and (108±17) minutes (range: 82 to 154 minutes), respectively. There were no death and serious complications (stroke, myocardial infarction, renal insufficiency, severe infection, etc.). The postoperative drainage volume within 24 hours was (314±145) ml (range: 130 to 830 ml). The intubation time was (14±3) hours (range: 8 to 21 hours), and the ICU time was ( M ( Q R )) 2.1(1.5) days (range: 1.0 to 5.0 days). Eight patients had no blood transfusion, the proportion of red blood cell use was 9.7% (3/31), plasma use was 22.6% (7/31), and platelet use was 71.0% (22/31). The postoperative left ventricular ejection fraction was (62±4)% (range: 54% to 69%), and left ventricular end-diastolic diameter was (48±4) mm (range: 39 to 56 mm). After operation, aortic regurgitation was significantly improved, with no more than moderate regurgitation, small to moderate regurgitation in 3 patients, minor regurgitation in 3 patients, micro regurgitation in 12 patients and no regurgitation in 13 patients. The follow-up period was 3.5(6.1) months (range: 2.0 to 39.0 months). Echocardiographic follow-up data were obtained in 26 cases, including moderate regurgitation in 1 patient, small to moderate regurgitation in 9 patients, minor regurgitation in 5 patients, micro regurgitation in 6 patients and no regurgitation in 5 patients. There were no major adverse cardiovascular events and aortic events during the follow-up period. No patient was reoperated for aortic regurgitation. Conclusion: Valve sparing aortic root replacement under partial upper sternotomy is safe and feasible, and the early result is satisfactory.

In vivo images of human cone photoreceptors have been shown to vary in their reflectance both spatially and temporally. While it is generally accepted that the unique anatomy and physiology of the photoreceptors themselves drives this behavior, the exact mechanisms have not been fully elucidated as most studies on these phenomena have been limited to the human retina. Unlike humans, animal models offer the ability to experimentally manipulate the retina and perform direct in vivo and ex vivo comparisons. The thirteen-lined ground squirrel and northern tree shrew are two emerging animal models being used in vision research. Both models feature cone-dominant retinas, overcoming a key limitation of traditional rodent models. Additionally, each possesses unique but well-documented anatomical differences in cone structure compared to human cones, which can be leveraged to further constrain theoretical models of light propagation within photoreceptors. Here we sought to characterize the spatial and temporal reflectance behavior of cones in these species. Adaptive optics scanning light ophthalmoscopy (AOSLO) was used to non-invasively image the photoreceptors of both species at 5 to 10 min intervals over the span of 18 to 25 min. The reflectance of individual cone photoreceptors was measured over time, and images at individual time points were used to assess the variability of cone reflectance across the cone mosaic. Variability in spatial and temporal photoreceptor reflectance was observed in both species, with similar behavior to that seen in human AOSLO images. Despite the unique cone structure in these animals, these data suggest a common origin of photoreceptor reflectance behavior across species. Such data may help constrain models of the cellular origins of photoreceptor reflectance signals. These animal models provide an experimental platform to further explore the morphological origins of light capture and propagation.

Objective: We aimed to evaluate the incidence of organ cysts in patients with type A aortic dissection (TAAD) to assess the association between organ cysts and TAAD., Methods: Between January 2018 and December 2018, all patients with TAAD undergoing aortic surgery at our center were enrolled into the study; patients undergoing isolated coronary artery bypass grafting at our center were selected as the control group. Baseline differences between the 2 groups were adjusted using propensity-score matching. The incidence of organ cysts was compared between the 2 groups in total and matched cohorts., Results: We enrolled 290 patients with TAAD and 293 patients with coronary artery disease (control group). The incidence of all organ cysts, liver cysts, renal cysts, and other organ cysts, was significantly higher in the TAAD group than in the control group (50.0% vs. 35.5%, p<0.001; 24.5% vs. 10.2%, p<0.001; 33.4% vs. 24.9%, p=0.023; and 6.2% vs. 1.5%, p=0.005; respectively). Among the 191 propensity score-matched patient pairs, the incidence of organ cysts, liver cysts, renal cysts, and other organ cysts was also significantly higher in the TAAD group than in the control group (57.6% vs. 30.9%, p<0.001; 28.8% vs. 11.0%, p<0.001; 39.3% vs. 19.9%, p<0.001; and 8.4% vs. 1.0%, p=0.001; respectively). The incidence of cysts with single-organ and multiple-organ involvement was also significantly higher in the TAAD group than in the control group (34.0% vs. 20.4%, p=0.003; and 23.6% vs. 10.5%, p=0.001)., Conclusion: Our results show a higher incidence of organ cysts in patients with TAAD which is indicative of a common pathogenetic pathway between organ cysts and aortic dissection.

Objective: To preliminarily investigate effectiveness and safety of sutureless integrated stented graft (SIS graft) on aortic dissection patients undergoing surgeries. Methods: In October 2019, 2 patients with aortic dissection were treated by SIS graft in Shenzhen Fuwai Hospital. Data of the operations and follow-up were recorded. Results: Patient 1 (male, 42 years old) was treated with aortic sinus repair, ascending aortic replacement, total arch replacement combined with frozen elephant trunk implantation. Time of cardiopulmonary bypass and circulatory arrest was 81 minutes and 9.5 minutes,respectively. The lowest nasopharynx temperature was 27.3 ℃. This patient was followed up for 10 months and no postoperative complication was found. Six-month postoperative aortic CT angiography (CTA) revealed SIS graft was patent and no anastomosis fistula or stent leakage occurred. True lumen of stented area was full-filled and false lumen disappeared. Incomplete false lumen thrombosis was seen in un-stented thoracic aorta, but no progressive aortic enlargement appeared. Patient 2 (male, 61 years old) was treated with ascending aortic replacement, ascending aorta to right femoral artery bypass graft, total arch replacement combined with frozen elephant trunk implantation. Time of cardiopulmonary bypass and circulatory arrest was 77 minutes and 7 minutes,respectively. The lowest nasopharynx temperature was 27.3 ℃. This patient was also followed up for 10 months and was free of postoperative complications. Six-month postoperative aortic CTA revealed SIS graft was patent and there was no anastomosis fistula or stent leakage. Perfusion of true lumen in thoracic aorta and branches of abdominal aorta improved significantly and complete false lumen thrombosis could be seen in thoracic aorta. Progressive aortic enlargement was not detected. Conclusion: Application of SIS graft can reduce circulatory arrest time and avoid deep hypothermia, which will decrease risks of postoperative complications, and this graft can simplify surgery procedure. However, further clinical trial for effectiveness and safety of SIS graft should be applied.

Background: Valve-related hemodynamics and intrinsically regulated matrix proteases are 2 determined pathogenetic factors associated with medial elastin degeneration in bicuspid aortopathy. This study analyzed the association between elastic fiber deterioration and the 2 pathogenetic factors in ascending and root morphotypes, aiming to elucidate the etiological heterogeneity between the 2 morphotypes., Methods: Four-dimensional flow cardiac magnetic resonance was used to measure the regional wall shear stress (WSS) on the ascending aorta, and matrix metalloproteinase (MMP) expression was assessed by immunoblotting. After histopathology analysis of aortic tissue, we assessed whether elevated regional WSS and increased MMP expression corresponded with medial elastin thinning., Results: Increased regional WSS corresponded with medial elastin thinning in both morphotypes. Increased expression of different MMP isoforms corresponded with medial elastin degeneration in bicuspid aortopathy. The significantly increased expression of MMP-2 corresponded with a decrease of elastic fiber thickness in the ascending morphotype (P = .046), whereas elastic fiber thinning was associated with high levels of MMP-3 expression (P = .012) in the root morphotype. No association was observed between regional WSS and MMP expression., Conclusion: There is no difference in the effect of valve-related hemodynamics between ascending and root morphotype, and MMPs are not involved in the process of elastic fiber degeneration induced by increased WSS. The increased expression of different MMP isoforms was observed in the context of elastic fiber degeneration between the 2 morphotypes, implying that heterogeneity between them is revealed in the different intrinsic pathway of medial elastin degradation.

Background: Aortic arch disease with Kommerell's diverticulum is an uncommon but troublesome condition, and there are a variety of therapeutic modalities for treating this. We retrospectively analyzed cases who underwent open surgery to summarize different situations and approaches., Methods: From November 2015 to January 2019, nine patients underwent operation for the mentioned disorder. Four patients with aortic dissection received total arch replacement. Two patients suffering from type B aortic dissection (TBAD) have accepted graft replacement from ascending aorta (aAO) to descending aorta. Two patients with true aneurysm and congenital malformation underwent graft bypass from aAO to descending aorta. One patient had graft replacement of descending aorta., Results: There were nine (eight males and one female) patients with median age of 45 (from 14 to 54) years. The 30-day mortality was 11.1% (1 patient) due to refractory respiratory failure caused by compression of bronchus. One patient had complication of peripheral neuropathy and recovered eventually. Eight patients were followed-up for a median period of 20 [9-46] months. All patients were alive and had no long-term complications except one patient who received re-intervention due to delayed dilation of downstream aorta., Conclusions: Treatment for different arch lesions with Kommerell's diverticulum should follow corresponding indications. Open surgery is the preferred choice and detailed therapeutic strategy depends on the extension of aneurysm, classification and phase of dissection. Stenting might cause airway compression when right-sided arch and vascular ring exist., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1602). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Aortic dissection is a life-threatening cardiovascular disease. Multi-center registration databases for aortic dissection have been established in many countries. The International Registry of Acute Aortic Dissection has produced a number of research results, which had a significant impact on the diagnosis and treatment of aortic dissection worldwide. The Society for Thoracic Surgeons Adult Cardiac Surgery Database summarizes perioperative data on aortic dissection. German Registry for Acute Aortic Dissection Type A has made remarkable achievements in the neurological protection and organ perfusion of type A aortic dissection. The Nordic Consortium for Acute Type A Aortic Dissection provides guidelines for perioperative administration of aortic dissection. However, the first Registry of Aortic Dissection in China (Sino-RAD) has not reported any new aortic dissection data in the past five years, although it has proposed a number of pathogenic characteristics of Chinese people. Therefore, it is necessary to establish our own aortic dissection database.

Bromodomain-containing protein 4 (BRD4) is a cancer therapeutic target in ongoing clinical trials disrupting primarily BRD4-regulated transcription programs. The role of BRD4 in cancer has been attributed mainly to the abundant long isoform (BRD4-L). Here we show, by isoform-specific knockdown and endogenous protein detection, along with transgene expression, the less abundant BRD4 short isoform (BRD4-S) is oncogenic while BRD4-L is tumor-suppressive in breast cancer cell proliferation and migration, as well as mammary tumor formation and metastasis. Through integrated RNA-seq, genome-wide ChIP-seq, and CUT&RUN association profiling, we identify the Engrailed-1 (EN1) homeobox transcription factor as a key BRD4-S coregulator, particularly in triple-negative breast cancer. BRD4-S and EN1 comodulate the extracellular matrix (ECM)-associated matrisome network, including type II cystatin gene cluster, mucin 5, and cathepsin loci, via enhancer regulation of cancer-associated genes and pathways. Our work highlights the importance of targeted therapies for the oncogenic, but not tumor-suppressive, activity of BRD4., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Thrombin activates protease-activated receptor-1 (PAR-1) through binding to exosite I and the active site to promote tumor growth. We have developed a new class of anti-cancer glyco-peptides to target exosite I selectively without affecting the active-site-mediated coagulation activity and showed the importance of glycans for the stability and anti-cancer activity of the glyco-peptides.

Objective To investigate the risk factors associated with acute renal failure (ARF) after thoracoabdominal aortic aneurysm (TAAA) surgery. Methods A total of 156 patients underwent TAAA repair between January 2009 and December 2017. Renal failure was defined based on the Kidney Disease Improving Global Outcomes criteria. The patients were divided into ARF group and non-ARF group based on the presence/absence of postoperative ARF. The risk factors of ARF were analyzed by univariate analysis and multivariate logistic analysis. Results The subjects included 111 males and 45 females aged (40.4±10.9) years (range:19-65 years). The surgical reasons included aortic dissection ( n =130,83.3%),aneurysm ( n =22,14.1%),and pseudoaneurysm ( n =4,2.6%). The degrees of repair included Crawford extent I in 6 patients (3.8%),extent Ⅱ in 128 patients (82.1%),extent Ⅲ in 20 patients (12.8%),and extent Ⅳ in 2 patients(1.3%). There were 3 patients presented with aortic rupture and 6 patients received emergent operations. Nine patients (5.8%) died within 30 days after surgery,and 8 patients (5.1%) suffered from permanent paraplegia. Thirty-six patients (23.1%) had ARF after surgery,and 18 of them needed dialysis. Multivariate logistic analysis showed that smoking ( OR =2.637,95% CI =1.113-6.250, P =0.028),packed red blood cell usage in operation (≥6 U) ( OR =5.508,95% CI =2.144-11.930, P =0.000),reoperation for bleeding ( OR =3.529,95% CI =1.298-9.590, P =0.013) were independent risk factors for ARF after TAAA repair. Conclusion Smoking,packed red blood cell usage in operation (≥6 U),reoperation for bleeding are the independent risk factors of ARF after TAAA surgery.

Iloprost, a stable prostaglandin I 2 (PGI 2 ) analog, can inhibit allergic inflammation in an ovalbumin (OVA)-induced asthma model via inhibition of airway dendritic cell (DC) function. However, the underlying mechanism of PGI 2 signaling-mediated immunosuppression remains unclear. This study explored whether iloprost-treated DCs can suppress inflammation by promoting antigen-specific regulatory T cell (Treg) differentiation through PGI 2 -G-protein-coupled receptor (IP). We established an allergic lung inflammation model using a hydrogel biomaterial delivery system and observed that iloprost significantly suppressed OVA-induced Th2 lung inflammation and increased the frequency of OVA-specific Tregs in vivo. We further observed that iloprost-treated DCs displayed tolerogenic characteristics, including low inflammatory cytokine (IL-12, TNF-α, IL-6, IL-23) expression levels, high anti-inflammatory cytokine (IL-10) production, and a semimature phenotype. In addition, iloprost-treated DCs increased OVA-specific CD4 + Foxp3 + T cell differentiation from naïve T cells in an IP-dependent pathway in vitro and in vivo. Blocking experiments showed that iloprost-treated DCs promoted Treg differentiation, at least in part, through programmed death ligand 1 (PD-L1), whereas iloprost-induced PD-L1 expression in DCs was through the IP receptor. Furthermore, iloprost treatment suppressed DC-mediated airway inflammation and increased the frequency of OVA-specific Tregs through PD-L1 in vivo. Taken together, these results show that PGI 2 -IP signaling mediated by iloprost in DCs may lead to immune tolerance, suggesting that the PGI 2 analog has the potential to be applied therapeutically for tolerogenic DC immunotherapy in autoimmune diseases or allergic asthma., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4-related diseases (IgG4-RD). The possible role of IgG4-positive plasma cells in calcifying fibrous tumour was investigated. The aim of this study was to determine any potential relationship between IgG4-RD and CFT. Thirteen cases with a total of 16 CFTs were reviewed. Lesion samples were immunostained with anti-IgG4 and anti-IgG antibodies. The number of IgG4-positive and IgG-positive plasma cells (IgG + PC) and their ratios were estimated. Plasma cells were found in all tumours. IgG4-positive plasma cells ranged from 0 to 71 per high-power field (HPF; mean 17.8/HPF), and IgG + PC ranged from 2 to 93/HPF (mean 42.6/HPF). The IgG4/IgG ratio ranged from 0% to 80% (mean 29%). There were seven tumours with the ratio of IgG4/IgG + PC that exceeded 40%. Various degrees of stromal fibrosis were present in eight tumours. All tumours have variable calcification. The histopathological features of CFT were found to be similar to those of IgG4-RD. Some CFT also showed a high number of IgG4-positive plasma cells, and the ratio of IgG4/IgG + PC exceeded 40%, most notably in patients with concomitant inflammatory or autoimmune disease. The long-term follow-up showed no evidence of IgG4-RD in any of these patients. Our findings suggest that while CFT overlaps morphologically with IgG4-RD, it probably should not be classified as an IgG4-RD., (©2020 Company of the International Journal of Experimental Pathology (CIJEP).)

Objective: Kommerell diverticulum with aortic dissection involving aortic arch is a rare but troublesome condition. The purpose of this study is to summarize the experience and strategy of surgical treatment., Method: From November 2015 to January 2018, seven consecutive patients underwent surgical treatment in our institution. Three patients with acute type A aortic dissection and one patient with acute type B aortic dissection received total arch replacement and frozen elephant trunk (FET) implantation through median sternotomy. Three patients with chronic type B aortic dissection underwent total aortic arch and descending aorta replacement through median sternotomy and lateral thoracotomy., Result: There were seven male patients whose median age was 42.3 ± 11.7 (from 14 to 54) years old. There was no perioperative death in this study. One patient had postoperative critical illness polyneuropathy and required prolonged mechanical ventilation (485 hours) and recovered finally. Follow up was completed for all seven patients with a median follow-up time of 7 (3-46) months. One patient with type A dissection developed aneurysm of the descending aorta distal to the FET and received reintervention. No clinical events and abnormal computed tomography manifestations were found in the other seven patients., Conclusion: Total arch replacement and FET through single median incision is a reliable method for Kommerell diverticulum associated with acute dissection involving arch. For Kommerell diverticulum associated with chronic type A or B aortic dissection involving aortic arch, graft replacement by double or single incision is safe and appropriate., (© 2019 Wiley Periodicals, Inc.)

Schizophrenia is a basic self-disturbance that in its early stages causes the sufferer discomfort toward feelings of self. Therefore, fragility or abnormality with regard to sense of self was a core observation of early schizophrenia theory. Rather than body-image-related depression or anorexia, disturbed body experience is the main factor affecting body image in patients with schizophrenia. This is a concept that has been discussed in the literature in recent years. This article will introduce the body self model, discuss the schizophrenic symptoms that influence experienced body disturbances and reduce body self-functions, and explore the relationship between body identity and body image. In order to improve the body image of patients with schizophrenia, it is necessary to conduct assessments and interventions that enhance the sense of body identity.

Objective To evaluate the early and midterm results of surgical repair of thoracoabdominal aortic aneurysm(TAAA)in patients with Marfan syndrome(MFS). Methods The clinical data of patients with MFS undergoing TAAA repair in Fuwai Hospital between January 2009 and December 2017 were retrospectively analyzed.These patients were divided into two groups:MFS group( n =58)and non-MFS group( n =98).The baseline data,early postoperative results,and midterm follow-up outcomes were compared between these two groups. Results MFS patients were significantly younger(32 years old vs. 45 years old, t =9.603, P =0.000)and more frequently had a history of aortic aneurysm or dissection(19% vs. 0, χ 2 =19.996, P =0.000)than non-MFS patients.However,the proportions of males and smokers were significantly lower when compared with non-MFS patients(55.2% vs. 80.6%, χ 2 =11.489, P =0.001;13.8% vs. 46.9%, χ 2 =17.686, P =0.001).There was no significant difference in proportion of emergency operation,prophylactic cerebrospinal fluid drainage,operation time,intra-operative circulation management,and intra-operative blood transfusion(all P >0.05).The 30-day mortality rate was significantly lower in MFS group than in non-MFS group(0 vs. 9.2%, [Formula: see text]=5.034, P =0.025). Conclusions For patients with MFS,TAAA repair provides lower 30-day mortality and comparative middle-term survival.However,the re-intervention rate is higher among MFS patients,highlighting the importance of close follow-up.

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression and metastasis, but the functional roles of these GSLs and the key enzyme β1,3-galactosyltransferase V (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of β3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globo-series GSLs in breast cancer cells form a complex in membrane lipid raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) which then interact with AKT and receptor-interacting protein kinase (RIP), respectively. Knockdown of β3GalT5 disrupts the complex and induces apoptosis through dissociation of RIP from the complex to interact with the Fas death domain (FADD) and trigger the Fas-dependent pathway. This finding provides a link between SSEA3/SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor progression and apoptosis and suggests a direction for the treatment of breast cancer, as demonstrated by the combined use of antibodies against Globo-H and SSEA4., Competing Interests: The authors declare no conflict of interest.

Objectives: This study aimed to investigate the morphological characteristics of the dissected thoracic aorta and brachiocephalic arteries within the Chinese population., Methods: A retrospective analysis of computed tomography scans of 387 patients with acute Type A aortic dissection was carried out. The dimensions of the thoracic aorta at multiple levels and other imaging characteristics were studied., Results: The patients with a maximum diameter ≥55 mm accounted for less than one-third of the population. Among those without Marfan syndrome (MFS) (n = 349), only 114 (32.8%) patients had a maximal aortic diameter ≥ 55 mm, whereas among those with MFS (n = 38), 20 (78.9%) had a maximal aortic diameter ≥ 45 mm. The predicted maximum aortic diameter is 88.46 - 0.81 × height (cm) + 63.02 × body surface area (m2) + 5.50 × (if diabetes, 1, if not, 0) - 6.63 × (if hypertension, 1, if not, 0). A positive correlation was established between a circular false lumen and the probability that brachiocephalic arteries were involved by dissection. The size ratio of false lumen to true lumen was greater in the circumferential group when compared with the crescent group. The independent predictors for the circumferential false lumen were age, atherosclerosis and smoking., Conclusions: Herein, the morphological characteristics of the thoracic aorta among Chinese patients with acute Type A aortic dissection were described. The currently recommended criteria for prophylactic aorta surgery were applied to most patients with MFS but not to those without MFS within the Chinese population. Furthermore, the shape of the false lumen was identified as a putative risk factor that might affect the prognosis of the patients.

[This corrects the article DOI: 10.18632/oncotarget.24146.].

Plant protoplasts are useful for assessing the efficiency of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mutagenesis. We improved the process of protoplast isolation and transfection of several plant species. We also developed a method to isolate and regenerate single mutagenized Nicotianna tabacum protoplasts into mature plants. Following transfection of protoplasts with constructs encoding Cas9 and sgRNAs, target gene DNA could be amplified for further analysis to determine mutagenesis efficiency. We investigated N. tabacum protoplasts and derived regenerated plants for targeted mutagenesis of the phytoene desaturase (NtPDS) gene. Genotyping of albino regenerants indicated that all four NtPDS alleles were mutated in amphidiploid tobacco, and no Cas9 DNA could be detected in most regenerated plants., (© 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Objective: To investigate theperiodic changes in onset of aortic dissection. Methods: The clinical data of 1 121 patients with acute aortic dissection from Hebei province, treated at Fuwai hospital from January 1, 2010 to December 31, 2016, were collected and analyzed retrospectively. The regularity for the onset of aortic dissection was analyzed according to daytime (1:00 to 6:00, 7:00 to 12:00, 13:00 to 18:00, and 19:00 to 24:00), weekday, month, and quarter. Meanwhile,the differences in various type of aortic dissection patient were also compared. Results: The patients were (51.4±12.0) years old,77.88% (873 cases)were male and 69.05% (774 cases) were type A aortic dissection.The peak period for the onset of the disease in a day was from 13:00 to 18:00 (401 cases. 35.77%),and disease onset was less frequent from 1:00 to 6:00 (196 cases, 17.48%).The peak weekday of disease onset was Monday (173 cases, 15.43%) , and disease onset was less frequent on Friday (153 cases, 13.65%) . The peak month of disease onset was January (135 cases, 12.04%), and disease onset was less frequent in July(54 cases, 4.82%). The peak season of disease onset was winter (349 cases, 31.13%), and disease onset was less frequent in summer (184 cases, 16.41%). Number of disease onset was similar between ≥65 years old and<65 years old groups, with or without hypertension groups, with or without Marfan syndrome groups at different periods of a day, each weekday, and seasons(all P> 0.05). Conclusion: There are periodic changes in the onset of acute aortic dissection,which is higher in winter than in summer, higher in the afternoon than in the morning.

Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated., Results: Blood monocytic S100A9 + MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9 + MDSCs in PBMC were well correlated to tumor infiltrating CD68 + and S100A9 + cells, suggesting an origin of TAMs. Patient's MDMs, mostly from S100A9 + MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown., Conclusions: In conclusion, blood S100A9 + MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway., Methods: Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflict of interests

Objective: To explore the relationship between the incidence of aortic dissection and climate change. Methods: The characteristics of 345 acute aortic dissection patients came from Beijing in Department of Vascular Surgery, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College from January 2005 to December 2015 were analyzed, retrospectively. There were 266 male and 79 female patients with a mean age of (49±12) years. There were 209 cases of Stanford type A aortic dissection, and 136 cases of type B. According to Fuwai aortic dissection classification: type A 8 cases, type B 95 cases, type Cp 13 cases, type Ct 187 cases, type Cd 40 cases, type D 2 cases. Meanwhile, monthly maximum temperature, minimum temperature, average temperature, average pressure, amount of rainfall, sunshine, relative humidity and other meteorological data were collected. Rank-sum test was used to analyze the difference of onset of aortic dissection in different seasons and months. Generalized additive models were implied to explore climate change and the onset of aortic dissection. Results: The onset of aortic dissection was related to season. Winter had higher morbidity compared to summer ( M ( Q(R) ): 3(2) vs . 2(2), Z =1.97, P =0.05). The occurrence of aortic dissection was associated with month.December had the largest quantity, July had the least (2(3) vs . 2(1), Z =2.42, P =0.02). The mean temperature was statistically significant for indicating the change of aortic dissection onset. It meaned that onset probability was increased with the decrease of temperature ( RR =1.01, 95% CI: 1.00 to 1.02, P =0.04). Conclusions: The onset of aortic dissection had something to do with season and month. The incidence of aortic dissection increases with temperature decreases.

Background: HIV has become a chronic disease. Therefore, the mental health and sleep quality of people living with HIV/AIDS (PLWHA) have become increasingly important issues of concern., Purpose: To explore the sleep quality, depression, anxiety, and self-esteem of PLWHA and the correlation between sleep quality and various related mental-health factors., Methods: A cross-sectional, descriptive, correlational study was conducted at a medical center in southern Taiwan in 2013-2014. Data on the sleep quality, depression, anxiety, and self-esteem of 146 PLWHA cases were collected using a structural questionnaire (the Pittsburgh Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, Zung's Self-Administered Anxiety Scale, and Rosenberg Self-Esteem Scale)., Results: Three-fifths (60.3%) of the cases had poor sleep quality, 50% were inclined toward depression, and 36.3% were inclined toward anxiety, indicating that sleep quality, depression, and anxiety levels in these cases were worse than the general population. Moreover, significant correlations were identified between poor sleep quality and the variables of depression (r = .40, p < .001) and anxiety (r = .53, p < .001). Multiple variate analysis revealed that older age, subjective feelings that HIV significantly influenced personal life, anxiety, and depression were all significant predictors of sleep quality. No significant correlations were found between CD4 (cluster of differentiation 4) lymphocyte count, HIV viral load, or receiving antiretroviral therapy and the variables of sleep quality, depression, anxiety, or self-esteem., Conclusions / Implications for Practice: About half of the PLWHA cases in the present study exhibited poor sleep quality and tendencies toward depression and anxiety. Moreover, sleep quality and mental health factors were found to be not correlated with CD4 lymphocyte count, HIV viral load, or receiving antiretroviral therapy. Therefore, early evaluation of the sleep quality and mental health of people living with HIV/AIDS is recommended in order to provide holistic care.

Cinnamaldehyde (CA), the primary chemical component of the Chinese traditional herb Cinnamomum cassia, is an effective cytotoxic agent against various human cancers. Our previous study indicated that CA could trigger apoptosis in three kinds of non-small cell lung cancer (NSCLC) cells. However, CA mechanism of action in NSCLC has not been unveiled completely. Herein, we showed that a novel circular RNA hsa&#95;circ&#95;0043256 was upregulated in NSCLC cells in response to CA treatment, as detected by microarray and real-time PCR. Hsa&#95;circ&#95;0043256 could inhibit cell proliferation and induce apoptosis, while hsa&#95;circ&#95;0043256 knock-down could promote cell proliferation and restrain apoptosis induced by CA. Bioinformatics analysis predicted that hsa&#95;circ&#95;0043256 could work as a miR-1252 sponge, which could in turn directly target a vital negative regulator of Canonical Wnt signaling, Itchy E3 ubiquitin protein ligase (ITCH), as validated by dual-luciferase assay. Western blot results further confirmed that hsa&#95;circ&#95;0043256 could upregulate ITCH expression, whereas miR-1252 could partially abolish this effect. Interestingly, hsa&#95;circ&#95;0043256 knock-down could weaken Wnt/β-catenin pathway inhibition induced by CA. Finally, we discovered that CA induced apoptosis and meanwhile upregulated hsa&#95;circ&#95;0043256 expression in vivo. Immunohistochemical analysis revealed that ITCH expression was positively association with hsa&#95;circ&#95;0043256 levels. Above all, we characterized a new mechanism mediated by hsa&#95;circ&#95;0043256/miR-1252/ITCH axis in CA function against NSCLC, providing a novel insight into lung cancer therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this scoping review, the evidence of the benefits of screening older people for the five most common types of cancer in Hong Kong, namely colorectal, lung, breast, liver, and prostate cancers, is discussed. Although cancer treatments can be extensive and a good prognosis is less likely if cancer is diagnosed at a late stage, screening programmes for older people in primary care remain a matter of contention. The general recommendation for the screening of older people is to adopt an individualised approach that takes account of not only age but also co-morbidity, life expectancy, harms and benefits, and patient's preference.

The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment. Seventy-nine patients were treated with 40 mg/day and 67 received de-escalated doses of <40 mg/day. There was no significant difference in the clinical characteristics of the two groups except that the proportion of patients with a body weight of 50 kg or more was greater in the 40 mg/day group. Otherwise, there were no significant differences between the two groups in the average time to treatment failure (TTF), the rates at which the administration of a second-line therapy was necessary, or the frequency and severity of adverse events. Overall, these results suggest that it is possible to calibrate the dosage of afatinib to suit individual patient parameters such as low body weight, and that such calibration can be advised based on the given patient's individual experience of the drug., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Background: To retrospectively analyze the role of intercostal artery reconstruction in the spinal cord protection for patients undergoing extensive thoracoabdominal aortic aneurysm repair., Methods: From August 2007 to 2014, thoracoabdominal aortas (Crawford II) of 81 consecutive patients with mean age 39.4 ± 10.32 years were repaired. Seventy-three of these patients (90.12%) were diagnosed with aortic dissection in our group, 25 (30.86%) with Stanford type A dissection and 48 (59.26%) with Stanford B aortic dissection. All 25 patients with type A dissection have previously undergone surgical procedures which include Bentall's procedures in 11 cases, ascending aortic replacement in 6 cases, and total aortic arch replacement in 8 cases. All procedures were performed under profound hypothermia with interval cardiac arrest after making a thoracoabdominal incision. Extracorporeal circulation was instituted with 2 arterial cannulae and a single venous cannula in the right atrium. T6-T12 intercostal arteries and L1 and L2 lumbar arteries were formed to a neo-intercostal artery in place and were connected to an 8 mm branch for maintaining spinal cord blood perfusion. Visceral arteries were joined into a patch and anastomosed to the end of the main graft. The left renal artery was anastomosed to an 8 mm branch or joined to the patch. The other 10 mm branches were anastomosed to iliac arteries., Results: With 100% follow-up, early mortality was 7.4%. Six deaths were recorded; 1 patient died of cerebral hemorrhage, 3 of renal failure, 1 of heart failure because of myocardial infarction, and the last one died from the rupture of celiac artery dissection. The rate of postoperative spinal cord deficits was 3.7%, 2 patients with paraplegia and 1 patient with paraparesis. None had bladder or rectum dysfunction. Neo-intercostal arteries were clogged in 12 patients within follow-up period and formed pseudoaneurysm in 2 patients with Marfan syndrome. The mean survival time in this group was 54.22 ± 3.03 months (95% confidence interval 44.37-59.90 months) with survival rate of 92.37% after 1 year, 89.02% after 2 years, and 85.54% after 5 years. All patients were free from spinal cord deficits., Conclusions: Intercostal artery reconstruction is an effective technique for spinal cord protection in patients with the thoracoabdominal aortic repair. It can achieve favorable results and avoid spinal cord deficits with long-term follow-up., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions., Methods: From June 2010 to October 2012, 102 patients with lung adenocarcinoma, harboring favorable EGFR mutations and treated with EGFR-TKI were analyzed. Definite new lesions were detected during EGFR-TKI therapy, even though the primary target tumors were controlled., Results: Of the 102 patients, 57 continued and 45 discontinued EGFR-TKI therapy. The median overall survival was 529 days for the discontinuation group and 791 days for the continuation group (p = 0.0197). Median survival time after the discontinuation of EGFR-TKI was 181 days and 115 days in the discontinuation and continuation groups, respectively (p = 0.1776), whereas median survival time after the appearance of indolent new lesions was 204 days and 262 days, respectively (p = 0.0237)., Conclusion: Continuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions., (Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Cell fate specification is a critical process to generate cells with a wide range of characteristics from stem and progenitor cells. Emerging evidence demonstrates that the orphan nuclear receptor COUP-TFII serves as a key regulator in determining the cell identity during embryonic development. The present review summarizes our current knowledge on molecular mechanisms by which COUP-TFII employs to define the cell fates, with special emphasis on cardiovascular and renal systems. These novel insights pave the road for future studies of regenerative medicine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: The study aim was to compare the long-term effect of Western medicine and combined treatment with Traditional Chinese Medicine (TCM) and Western medicine on the prognosis (survival rate, symptom distress, physical function, and quality of life) of patients with lung cancer., Design: Longitudinal study., Setting/location: Two medical centers, one each in Northern and Southern Taiwan., Patients: Patients newly diagnosed with lung cancer and treated with Western medicine (n = 54) or TCM plus Western medicine (n = 30)., Outcome Measures: Symptom distress, physical function, and quality of life were measured by using the Symptom Distress Scale, Eastern Cooperative Oncology Group-Performance Status Rating, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and EORTC QLQ-LC13), respectively. Data on these measures were collected at baseline (before treatment) and 1, 3, 6, and 12 months after starting treatment. Survival was estimated by Kaplan-Meier curves. Group differences in outcomes were analyzed by generalized estimating equations., Results: Treatment groups did not differ significantly at baseline for demographic information; disease severity; symptom distress; or EORTC QLQ-C30 and QLQ-LC13 scores, except for pain and dyspnea. After adjustment for these baseline effects, the combined-treatment group had better physical function and role function than the Western medicine group at 6 months (p < 0.05). The combined treatment group had better cumulative survival, but this difference did not reach significance., Conclusions: To more precisely estimate the long-term effectiveness of combined treatment on the prognosis of patients with lung cancer, future studies should standardize the number of TCM visits; increase the number of participants by continuous recruitment; and ask patients to complete daily logs with single-item measures of outcomes, such as symptom distress, quality of life, and physical function. Similar studies are suggested in patients with different cancers to develop a collaborative model using Western medicine and TCM.

Fish is an important causative material of food allergy. Although the allergenicity of fish is considered to correlate with the content of parvalbumin, the major fish allergen, available information about the parvalbumin content in fish is limited. In this study, a simple and reliable quantification method for fish parvalbumin by SDS-PAGE was first established. Application of the SDS-PAGE method to 22 species of fish revealed a marked variation in parvalbumin content among fish. Furthermore, the parvalbumin content was found to be higher in dorsal white muscle than in ventral white muscle, in rostral part of white muscle than in caudal part of white muscle and in white muscle than in dark muscle. IgE reactivity of fish was roughly proportional to parvalbumin content. Interestingly, large-sized migratory fish, such as salmon, swordfish and tuna, were commonly very low in both parvalbumin content and IgE reactivity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background . We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans. Methods . We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs. Results . Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%). Conclusion . CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs., Competing Interests: The authors declare that they have no conflict of interests regarding the publication of this paper.

Human immunodeficiency virus (HIV)/AIDS is a manageable infectious disease by the effectiveness of highly active antiretroviral therapy. AIDS-related stigma and conflict may create distress and deteriorate quality of life (QoL) of people living with HIV/AIDS (PLWHA). This cross-sectional, descriptive, correlational study using structural questionnaires aimed to explore the stress, needs, QoL, and associated factors of PLWHA in Taiwan. A total of 200 PLWHA participating in this study needed most on treatment of HIV and prevention of AIDS, and health maintenance. They had worse QoL in physical, psychological, and social domains (all p < 0.001) than the general population. Stress was the most significant predictor (β = -0.25 to -0.54, p < 0.01) for all four domains of QoL. Needs was not significantly associated with QoL. The QoL of PLWHA can be explained by demographics, self-perception on health, needs, and stress for 25.3-40.7% of variances. No association existed between CD4(+) counts and QoL in Taiwanese PLWHA. It is important to recognize the perception of PLWHA on their health status, which is significantly associated with their QoL, besides monitoring their physical indicators of health (CD4(+) counts). To recognize the stress and needs that PLWHA experience and to develop intervention programs targeting strategies on HIV disclosure, prevention and health maintenance are crucial for PLWHA's QoL., (Copyright © 2015. Published by Elsevier Taiwan.)

Objectives: Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial., Methods: Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy: n = 56 and 2nd-line chemotherapy: n = 55). Their outcomes profiles were analyzed., Results: The overall survival (OS) of all patients (390 versus 662 days, p < 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days, p = 0.0001) and OS (308 versus 704 days, p = 0.0001) of patients with L858R mutation (n = 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, and L858R mutation were significantly related to poor PFS and OS., Conclusion: In advanced lung adenocarcinoma, L858R mutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.

Hepatoma upregulated protein (HURP) is originally isolated during the search for the genes associated with hepatoma. HURP is upregulated in many human cancers. Culture cells exhibit transformed and invasive phenotype when ectopic HURP is introduced, revealing HURP as an oncogene candidate. Our previous studies demonstrated that Aurora-A regulated the cell transforming activities of HURP by phosphorylating HURP at four serines. To unravel how the Aurora-A/HURP cascade contributes to cell transformation, we firstly noticed that HURP shuttled between cytoplasm and nucleus. The nuclear localization activity of HURP was promoted or abolished by overexpression or knockdown of Aurora-A. Similarly, the HURP phosphorylation mimicking mutant 4E had higher nuclear targeting activity than the phosphorylation deficient mutant 4A. The HURP 4E accelerated G1 progression and upregulated cyclin E1, and the cyclin E1 upregulating and cell transforming activities of HURP were diminished when the nuclear localization signal (NLS) was removed from HURP. Furthermore, HURP employed p38/nuclear factor-κB (NF-κB) cascade to stimulate cell growth. Interestingly, NF-κB trapped HURP in nucleus by interacting with HURP 4E. At last, the HURP/NF-κB complex activated the cyclin E1 promoter. Collectively, Aurora-A/HURP relays cell transforming signal to NF-κB, and the HURP/NF-κB complex is engaged in the regulation of cyclin E1 expression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Methylosome protein 50 (MEP50) is a component of methylosome where MEP50 binds protein substrates and activates the oncogenic protein arginine methyl transferase 5 (PRMT5). MEP50 is also a coactivator for androgen receptor (AR) and estrogen receptor (ER), and transforms cells in the presence of androgen or estrogen. To extend the understanding of how MEP50 transforms cells, we investigated whether MEP50 could transform cells independent of AR and ER, and clarified whether PRMT5 could contribute to the MEP50-caused tumor formation. Microarray and Western blot analyses revealed the association of MEP50 with many human cancers including lung cancer. Knockdown of MEP50 retarded cell growth and migration in selected lung cancer cell lines, which expressed very low level of AR and ER and were insensitive to inhibitors of AR and ER. Moreover, overexpression of Myc-MEP50 enhanced cell transforming activities of 293T cells which are known lack of expression of AR and ER. Mechanistic analyses showed that MEP50 controlled G2 progression, upregulated cyclin-dependent kinase 1(CDK1)/cyclin B1, and activated the survival cascade Phosphoinositide 3-kinase (PI3K)/AKT. MEP50 promoted cell migration, and activated the cell migration pathways such as Ras-related C3 botulinum toxin substrate 1 (Rac1)/vasodilator-stimulated phosphoprotein (VASP), and forkhead box protein A2 (FOXA2)/slug/cadherin cascades. Further analyses revealed that MEP50 activated the survival factor PI3K through PRMT5-catalyzed dimethylation of PI3K. Collectively, it is concluded that MEP50 can transform cells independent of AR and ER, and PRMT5 has partial contribution to that process., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Most of the patients with stage IIIA pN2 non-small cell lung cancer (NSCLC) develop recurrence after surgery. It is not clear whether post neoadjuvant chemotherapy tumor-associated macrophages is associated with recurrence., Patients and Methods: Stage IIIA pN2 NSCLC patients underwent cisplatin/docetaxel neoadjuvant chemotherapy and surgery were retrospectively enrolled. Immunohistochemical staining of CD68 was used to identify macrophages in surgical resected stored tissues., Results: The objective response rate of cisplatin/docetaxel was 68%, overall median disease-free survival (DFS) was 13.1 months and median overall survival (OS) 36.8. months. Multiple Cox regression analysis showed low total macrophage numbers and mediastinal lymph nodes downstaging were independent factors for longer DFS, whereas high islet/stromal macrophages ratio was an independent facto for OS. In patients downstaged to pN0, low total macrophage numbers was also associated with longer DFS., Conclusions: Low total macrophage number is an independent factor for better DFS in pN2 stage IIIA NSCLC patients receiving neoadjuvant chemotherapy and surgical resection, which association was kept in those downstaged to pN0. Further studies are warrant to confirm the predictive role of TAMs and their potential causative role in tumor recurrence.

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser(115). The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis., (Copyright © 2014 the American Physiological Society.)

Background: This study explored the effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy., Patients and Methods: For this experimental study, 57 subjects were randomly assigned to three groups: acupressure with essential oils (n=17), acupressure only (n=24), and sham acupressure (n=16). Acupoints were Hegu (LI4), Zusanli (ST36), and Sanyingjiao (SP6). All subjects received acupressure once every morning for 5 months, with each acupoint pressed for 1 min. Fatigue, functional status, anxiety, depression, and sleep quality were measured before initial chemotherapy (T0), on Day 1 of third chemotherapy (T1), and on Day 1 of sixth chemotherapy (T2). Outcome differences between groups were analyzed at T0, T1, and T2 by general estimating equations., Results: After controlling for baseline outcome values, age, and adherence to acupressure, subjects who received acupressure with essential oils and acupressure had significantly less fatigue in daily living activities and sleep better quality at T1 than subjects who received sham acupressure. Subjects who received acupressure with essential oils had significantly better sleep quality at T2 than the sham acupressure group. Subjects who received acupressure with or without essential oils had greater odds of better functional status at T1 than the sham group., Conclusion: It is plausible that acupressure with or without essential oils helps lung cancer patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level. Further study is wanted to test this hypothesis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)