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Background: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA., Methods: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient., Results: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients., Conclusions: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA., (© 2021 Wiley Periodicals LLC.)

Backgrounds: The pleating technique is widely used in plication but is difficult to perform with thoracoscopy because of its complex procedure and the limited surgical space. Thus, the invaginating technique was introduced to facilitate thoracoscopic surgery and is now widely used in video-assisted thoracoscopic surgery (VATS) plication. However, the usefulness of the invaginating technique in children has not been established because of the lack of data on long-term outcomes after surgery using the technique., Methods: From March 2007 to December 2017, 21 patients who were surgically treated for congenital diaphragmatic eventration and phrenic nerve palsy after congenital cardiac surgery were divided into 2 groups according to the surgical method used (pleating technique: 10 patients, invaginating technique: 11 patients). We evaluated the patients for postoperative outcomes and recurrence of diaphragmatic eventration over 5 years. Postoperative recurrence of diaphragmatic eventration was confirmed by calculating the ratio of the eventration level between the eventrated and normal diaphragms., Results: In the 21 patients who underwent diaphragmatic plication, the pleating and invaginating techniques were used in 10 and 11 patients, respectively. The mean follow-up duration was 63.4 ± 48.4 months (pleating group [P] vs invaginating group [I]: 89.1 ± 52.4 vs 40.1 ± 30.8 months, p = 0.022). The mean eventration rates in the 21 patients was 26.7% ± 9.1% (P vs I: 26.6% ± 6.1% vs 26.9% ± 11.3%, p = 0.945) before operation and -2.1% ± 7.3% (-2.8% ± 7.5% vs -1.5% ± 7.4%, p = 0.695) in the immediate postoperative period. From the first to the fifth postoperative year, no recurrence of diaphragmatic eventration was found in any of the groups during the follow-up., Conclusions: The invaginating technique was easier to perform but showed a similar long-term result as compared with the pleating technique in terms of the growth and development of the chest cavity in the pediatric patients in this study. Thus, we recommend that the invaginating technique be applied in VATS plication for children as an alternative to the pleating technique., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.

Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent-tumor-associated macrophages-and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.

We developed a modified Senning procedure in the double-switch operation for the patients with congenitally corrected transposition of the great arteries (ccTGA). In our technique, the right atrial (RA) free wall is not used as a baffle for draining systemic venous blood to the left atrium. Instead, a patch material is used for the baffling. A wide communication between the pulmonary venous chamber and RA is created by making the triangular double door with the RA-free wall, and the window is closed with in situ pericardial flap. We have successfully adopted this technique in our recent two consecutive ccTGA patients., (© 2020 Wiley Periodicals LLC.)

Early mitotic inhibitor 2 (EMI2, gene symbol FBXO43), an APC/C inhibitor regulated by Plx1, is essential for cytostatic factor (CSF) activity. It belongs to subclass FBXO of the F-box proteins family. The aim of this study is to examine the clinicopathological significance of EMI2 in breast cancer. In this study, immunohistochemistry analysis was used to evaluate EMI2 expression in breast cancer tissues and then the association between EMI2 expression and clinicopathological factors was examined. Correlation of EMI2 with patient survival was analyzed by Kaplan-Meier survival curves. Among 192 patients analyzed, 105 (54.7%) had high expression of EMI2, and this was significantly associated with shortened disease free survival and overall survival in breast cancer patients. EMI2 expression was significantly associated with tumor grade (P = .006), tumor size (P < .001), and lymph node metastasis (P = .008). However, there was no significant correlation between EMI2 status and other biomarkers including ER, PR and Her2 status. Our results revealed that elevated EMI2 expression is a risk factor (hazard ratio = 3.93) for breast cancer and overexpression of EMI2 in breast cancer predicts higher risk of metastasis and worse survival. Therefore, EMI2 may be a potential therapeutic target for breast cancer., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Resveratrol is a naturally occurring polyphenol compound which has been shown to possess antioxidant and anti-inflammatory properties. However, its pharmaceutical applications are limited by its poor water solubility. In this study, we used electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin (HPBCD) loaded with resveratrol. We used X-ray diffractometry to analyze crystalline structure, Fourier transform infrared spectroscopy to determine intermolecular hydrogen bonding, antioxidant assays to measure antioxidant activity, and Franz diffusion cells to evaluate skin penetration. Our results showed that the aqueous solubility of resveratrol nanofibers was greatly improved (by more than 20,000-fold) compared to the pure compound. Analysis of physicochemical properties demonstrated that following nanofiber formation, resveratrol was converted from a crystalline to amorphous structure, and resveratrol formed new intermolecular bonds with PVP and HPBCD. Moreover, resveratrol nanofibers showed good antioxidant activity. In addition, the skin penetration ability of resveratrol in the nanofiber formulation was greater than that of pure resveratrol. Furthermore, resveratrol nanofibers suppressed particulate matter (PM)-induced expression of inflammatory proteins (COX-2 and MMP-9) in HaCaT keratinocytes. Therefore, resveratrol-loaded nanofibers can effectively improve the solubility and physicochemical properties of resveratrol, and may have potential applications as an antioxidant and anti-inflammatory formulation for topical skin application.

Background: Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell carcinoma (ESCC) remains unclear., Patients and Methods: Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan-Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growth, migration, and invasion were examined using TE8, CE81T, and KYSE70 cells. The mechanisms involved were also analyzed. Nude mice models were used for assessment of tumor growth., Results: Rad51 staining was predominantly observed in ESCC patients. ESCC patients with high Rad51 expression had significantly decreased survival (P < 0.001) combined with increased tumor size (P = 0.034) and lymph node metastasis (P = 0.039). Rad51 overexpression promoted, while its knockdown attenuated, esophageal cancer cell viability through cell cycle entry and migration/invasion via epithelial-mesenchymal transition. Moreover, Rad51 overexpression increased colony formation in vitro and tumor growth in vivo. In addition, high Rad51 expression increased cancer progression through the p38/Akt/Snail signaling pathway., Conclusions: This study indicates a new biological role for Rad51 in ESCC progression. Rad51 may serve as a potential prognostic biomarker and therapeutic target for ESCC patients.

Oral potentially malignant disorder (OPMD) is associated with an increased risk of progression to oral cancer. Patients with dysplastic changes of the precancerous lesions have a higher malignant transformation rate than those without dysplastic changes. Radiotherapy and surgery are the traditionally preferred choices for OPMD treatment. However, side effects caused by radiotherapy and surgery may reduce the willingness of patients to accept therapy. Therefore, developing an Orabase-formulated drug, which can be non-invasively administered, may provide an alternative treatment choice. To find, verify, and develop a new anti-cancer drug cost a lot of time and money, while drug repurposing can shorten both time and cost. In this study, we utilized high-throughput screening library to identify clinical drugs, which may have new bioactivities. Herein, we report that benzalkonium chloride (BAK), an antimicrobial preservative for pharmaceutical products, significantly induced reactive oxygen species production and cell death in oral precancerous cells. Additionally, our results showed that phosphorylation of STAT3 (Tyr705) and Akt (Ser473) were involved in cell death caused by BAK in DOK cells. According to animal studies, the development of DMBA-induced oral precancerous lesions was inhibited by 2% BAK. In conclusion, Orabase-formulated BAK may be a potential treatment for OPMD in the future., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

To treat congenital heart disease, it is important to understand the anatomical structure correctly. Three-dimensional (3D) printed models of the heart effectively demonstrate the structural features of congenital heart disease. Occasionally, the exact characteristics of complex cardiac malformations are difficult to identify on conventional computed tomography, magnetic resonance imaging, and echocardiography, and the use of 3D printed models can help overcome their limitations. Recently, 3D printed models have been used for congenital heart disease education, preoperative simulation, and decision-making processes. In addition, we will pave the way for the development of this technology in the future and discuss various aspects of its use, such as the development of surgical techniques and training of cardiac surgeons., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2020 The Korean Society of Radiology.)

Prolonged pleural effusion after Fontan operation is a significant morbidity that leads to long hospital stays. We investigated the association of multiple risk factors, including clinical characteristics, hemodynamic parameters, and preoperative, operative, and postoperative factors, with prolonged pleural effusion after Fontan operation. Eighty-five patients who underwent a Fontan operation between January 2005 and June 2018 in our center were included in this retrospective study. Patients were divided into two groups: group 1 (n = 36, 42.4%) included those with prolonged pleural effusion, defined as lasting > 14 days after the Fontan operation, and group 2 included patients without prolonged pleural effusion. Patients with hypoplastic left heart syndrome (HLHS) were more prevalent in group 1 (n = 15, P = 0.006). No differences in age at Fontan operation, central venous pressure at Fontan operation, or hemodynamic parameters during the pre-Fontan evaluation were found between the two groups. In multivariable analysis, HLHS (P = 0.002), non-fenestration (P = 0.018), and high central venous pressure at bidirectional cavopulmonary shunt (BCPS) operation (P = 0.043) were independent risk factors for prolonged pleural effusion after Fontan operation. Adverse outcomes such as death, need for heart transplantation, and Fontan failure were not associated with prolonged pleural effusion. In conclusion, patients with HLHS and higher central venous pressure at BCPS were more likely to have a prolonged pleural effusion after Fontan operation, but fenestration was more likely to decrease prolonged effusion. We should consider closer management of fluid status before, during, and after surgery in patients with these risk factors after Fontan operation.

A concomitant anterior translocation of the right pulmonary artery (RPA) can be used in patients with airway compression by a dilated RPA associated with congenital heart disease having a large left-to-right shunt or aortic arch anomaly. However a chest wall deformity and mechanical compression of the anteriorly translocated RPA could develop after the operation. In this situation simple RPA angioplasty is not sufficient. Therefore we adopted a technique to perform a concomitant Nuss procedure in an effort to resolve this problem. After 8 months of follow-up a widely patent RPA and a normal appearance of the chest wall were confirmed., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Personal competencies are associated with successful job performance. Job satisfaction is directly related to nursing turnover, and is a critical indicator of their performance and quality of patient care. However, little is known about the relationship between personal competencies, social adaptation, and job adaptation on job satisfaction for nurses., Objectives: The purpose of this study was to explore the relationship between personal competencies, social adaptation, and job adaptation on job satisfaction for nurses., Design: This study was conducted with secondary data analysis., Settings: We targeted nursing alumni in a large university in Taiwan., Participants: The target population was nursing alumni, and the sample consisted of 280 from the Office of Student Affairs database., Methods: Personal competencies, social adaptation, job adaptation, and job satisfaction were measured using a secondary data analysis. Relationships between the variables were analyzed to determine which variable explained the most variance in job satisfaction., Results: Of the 280 participants, participation of extracurricular activities was reported by 70.4%, and over 22.5% had a leadership role in extracurricular activities. The results demonstrated that nursing alumni with either extracurricular activities involvement or a leadership role had higher level of personal competencies and better job satisfaction. Further, these results showed the number of years in the extracurricular activities (r = 0.174, p = .003), the perceived level of personal competencies (r = 0.341, p = .000), social adaptation (r = 0.411, p = .000) and job adaptation (r = 0.575, p = .000) were positively and significantly correlated with job satisfaction. The job adaptation, the perceived level of personal competencies, and alumni who had a leadership role accounted for 37.1% of variance in job satisfaction., Conclusions: Results of this study suggest that job adaptation, personal competencies, and having had a leadership role in extracurricular activities are important concepts to improving nurses' job satisfaction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center., Methods: Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed., Results: There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy., Conclusions: The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan., (© 2019 The International Society of Dermatology.)

Background: Conduit survival without significant dysfunction is important when selecting the right ventricular outflow tract conduit. We made an expanded polytetrafluoroethylene tricuspid valved conduit using a simplified technique. We aimed to investigate the midterm functional results and longevity of this conduit., Methods: Between November 2008 and December 2016, four hospitals in Korea implanted 145 valved conduits. We retrospectively analyzed their functional results and longevity., Results: The patients' median age at operation was 36.6 months; the median body weight was 11.3 kg. The mean follow-up duration was 32.3 ± 24.5 months. There were four inhospital deaths and three late deaths, but there were no conduit-related deaths. The mean peak systolic pressure gradient across the conduit was 14.7 ± 8.3 mm Hg and 31.6 ± 17.7 mm Hg at discharge and last follow-up, respectively. Six patients (4.4%) had moderate or more conduit valve regurgitation at last follow-up. Conduit dysfunction was observed in 30 patients (21.9%), mainly caused by increased pressure gradient (24 of 30, 80%). Freedom from conduit dysfunction was 88.1% and 58.5% at 3 and 5 years, respectively. Lower freedom from conduit dysfunction was observed in small conduits. Eleven patients (7.8%) underwent conduit explantation, and freedom from explantation was 94.8% and 81.7% at 3 and 5 years, respectively. The main cause of explantation was conduit stenosis. Small conduits tended to have lower freedom from explantation., Conclusions: Functional results and longevity of our expanded polytetrafluoroethylene tricuspid valved conduit are acceptable. Although our conduits tend to have increasing pressure gradient over time, especially in small conduits, they have low incidence of moderate or more regurgitation., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to determine if there was a difference between coronary reimplantation after neoaortic reconstruction and open coronary reimplantation technique in arterial switch operation (ASO)., Methods: A total of 236 patients who underwent ASO from March 1994 to August 2018 were enrolled in this study. Multivariate analysis was performed for postoperative early mortality. Patients were divided into the open coronary reimplantation and coronary reimplantation after neoaortic reconstruction groups. The 30-day mortality, intraoperative and postoperative coronary artery (CA) revisions, CA-related late morbidity and mortality, and early and late neoaortic valve regurgitations after ASO were compared between the two groups., Results: Overall postoperative early mortality was 7.2% (17/236). Patients who underwent open coronary reimplantation had higher early mortality as compared with those who underwent coronary reimplantation after neoaortic reconstruction. Risk factors for postoperative early mortality from multivariate analysis were cardiopulmonary bypass time and open coronary reimplantation. There was a higher incidence of CA-related late mortality or morbidity in the open coronary reimplantation group. The open coronary reimplantation group had a higher incidence of intraoperative or postoperative CA revision. There were no differences in the incidence of mild or more neoaortic valve regurgitation at discharge or in the 5-year freedom from mild or more neoaortic valve regurgitation., Conclusions: CA reimplantation after neoaortic reconstruction yields better results in mortality and intraoperative or postoperative CA-related problems in ASO without increasing postoperative neoaortic valve regurgitation.

Background: Skin aging can be classified as either physiological or pathological aging. Pathological aging is most often due to chronic sunlight exposure (photoaging). Age-dependent changes in dermoscopic features of normal skin have not previously been well defined., Objectives: We compared the dermoscopic features of skin from non-elderly subjects, elderly subjects with physiological aging, and elderly subjects with photoaging., Materials and Methods: We enrolled 40 non-elderly subjects aged 20-60 years, 40 elderly subjects aged >60 years with physiological aging, and 40 elderly subjects aged >60 years with photoaging. Skin from the lower legs of subjects was examined by dermoscopy., Results: Compared with non-elderly subjects, dermoscopic examination of elderly subjects with physiological aging and photoaging revealed various degrees of xerosis (mild: scaling limited to skin furrows; moderate: scaling extending beyond skin furrows with accentuation of skin markings; severe: plate-like scaling extending beyond skin furrows with formation of deep skin fissures). In addition, dermoscopic examination of skin from elderly subjects with photoaging showed increased prevalence of uneven pigmentation (small brown globules, reticular pigmentation, and homogeneous pigmentation in a patchy distribution) and vascular telangiectasia (linear and branching vessels)., Conclusion: This study provides a novel dermoscopic grading system to evaluate the severity of xerosis and demonstrates the application of dermoscopy for the accurate assessment of subtle morphological changes (including pigmentation pattern and vascular structures) associated with physiological aging and photoaging.

Background: Avicequinone-B (Naphtho[2,3-b]furan-4,9-dione) is a furanonaphthoquinone derivative. It is a hydrophobic compound with poor aqueous solubility, which may restrict its potential pharmaceutical and biomedical applications., Purpose: We synthesized different liposomal formulations of Avicequinone-B, and measured their particle size, aqueous solubility, and physicochemical properties. In addition, we investigated the anticancer activity of liposomal Avicequinone-B in human cutaneous squamous cell carcinoma (SCC) cells., Methods: Liposomal Avicequinone-B formulations were synthesized using the thin-film hydration method. Drug yield, encapsulation efficiency and aqueous solubility were determined by high performance liquid chromatography. Particle size and polydispersity index were measured by submicron particle size analyzer, and ultrastructural morphology was visualized by transmission electron microscopy. Thermal transitions were determined by differential scanning calorimetry. Anti-skin cancer activity was determined in HSC-1 cells (human cutaneous SCC cell line) using the MTS cytotoxicity assay, apoptosis was assessed by caspase-3/7 activity assay, mitochondrial membrane potential was determined by JC-10 assay, and signal transduction pathways were evaluated by Western blot analysis., Results: Liposomal Avicequinone-B formulations showed adequate yield and high encapsulation efficiency. These liposomal formulations produced small, uniformly sized nanoparticles, and greatly increased the aqueous solubility of Avicequinone-B. Differential scanning calorimetry showed loss of thermal phase transitions. In addition, liposomal Avicequinone-B showed significant cytotoxic effect on HSC-1 cells, through reduction of mitochondrial membrane potential, increased cytosolic cytochrome-c level, increased cleaved caspase 8 level, and induction of apoptosis. This was mediated through activation of ERK, p38 and JNK signaling pathways., Conclusion: Liposomal Avicequinone-B demonstrated improved aqueous solubility and physicochemical characteristics, and induced apoptosis in cutaneous SCC cells. Therefore, liposomal Avicequinone-B may have potential uses as a topical anti-skin cancer drug formulation in the future., (Copyright © 2019. Published by Elsevier GmbH.)

The epidemiology of depression in patients with psoriasis has not been well defined in the Asian population. This study evaluated the epidemiological features of, and risk factors for, depression among patients with psoriasis in Taiwan. A nationwide population-based cross-sectional study was undertaken using the National Health Insurance Research Database. This study included 17,086 patients with psoriasis and 1,607,242 patients from the general population. The prevalence of depression in patients with psoriasis was 11.52%, while the prevalence of depression in the general population was 7.73% (prevalence ratio 1.49, 95% confidence interval 1.43-1.55). Multivariable analysis showed that, in patients with psoriasis, risk factors associated with depression were: age 20-50 years, female sex, low income, and major comorbid diseases, including liver cirrhosis, renal disease, cardiovascular disease and cerebrovascular disease. Therefore, the prevalence of depression is higher in patients with psoriasis, particularly in young and middle-aged women with low income and major comorbidities.

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

Background: Saikosaponin-d (SSD) is a triterpene saponin isolated from Bupleurum plants. It has been shown to exhibit antioxidant, anti-inflammatory, and anticancer activities. However, its biomedical applications are limited by its poor water solubility. Cyclodextrins are highly water soluble oligosaccharide compounds which can form inclusion complexes with lipophilic drugs., Purpose: We complexed SSD with hydroxypropyl-β-cyclodextrin (HPBCD) in various ratios to form SSD-HPBCD inclusion complexes. The inclusion complexes were evaluated for their solubility, physicochemical properties and cytotoxic effects in cutaneous squamous cell carcinoma cells., Methods: Surface morphology of pure SSD and SSD-HPBCD inclusion complexes was evaluated by scanning electron microscopy. Crystalline structure was determined by X-ray diffractometry. Intermolecular hydrogen bond formation between SSD and HPBCD was investigated by Fourier transform infrared spectroscopy. Human cutaneous squamous cell carcinoma HSC-1 cell viability was determined by the MTS assay, and cell apoptosis by the caspase 3/7 assay. Signal transduction pathways were investigated by Western blotting., Results: SSD-HPBCD inclusion complexes showed greatly increased water solubility. This was associated with an improvement in physicochemical properties, including transformation of crystalline structure to amorphous form, and formation of hydrogen bonds between SSD and HPBCD. In addition, SSD-HPBCD inclusion complexes induced apoptosis in HSC-1 cells, and this was mediated through activation of MAPK and suppression of Akt-mTOR signaling pathways., Conclusion: SSD-HPBCD inclusion complex shows improvement in water solubility and physicochemical properties, and exhibits anticancer effects against cutaneous squamous cell carcinoma cells. Therefore, it may be a potential drug formulation for the treatment of skin cancer., (Copyright © 2018. Published by Elsevier GmbH.)

Coronary reimplantation after neoaortic reconstruction (CRANR) in the arterial switch operation (ASO) allows easy selection of accurate coronary transfer sites in the distended neoaorta. However, neoaortic valve injury may occur during coronary reimplantation. We determined whether the CRANR procedure increased the incidence of aortic valve regurgitation (AR) after ASO. Between March 1994 and August 2017, 227 patients underwent ASO. Since September 2000 CRANR has been performed on 155 patients and open coronary reimplantation (OCR) on 72. Patients who had undergone aortocoronary flaps procedures (n = 13), had early or late mortality (n = 27), or lacked data (n = 11) were excluded. We enrolled and retrospectively reviewed the medical records of 176 patients who were followed up for postoperative AR: 38 underwent OCR and 138 underwent CRANR. We compared the incidences of early and late postoperative AR in both groups. We defined mild or greater AR as "significant AR." The groups did not differ in body weight at operation, great artery relationship, and coronary artery anatomy. The incidences of significant AR at discharge were 21.1% (8/38) in the OCR group and 16.6% (23/138) in the CRANR group (p = 0.53). The freedom from significant AR at 5 years was 59.9% in the OCR group and 62.4% in the CRANR group with no difference between the two groups (p = 0.73). Moderate AR occurred in one patient in the CRANR group. No surgical intervention was required for the aortic valve in either group. ASO using the CRANR technique did not increase the incidence of postoperative early and late AR.

Introduction: Family history of psychopathology is a risk factor for mood and anxiety disorders in children, but little is known about rates of parental psychopathology among treatment-seeking youth with affective disorders in the Asia Pacific region. This study examined patterns of emotional and behavioural problems in parents of clinically-referred youth in Singapore. We hypothesised that parents would have higher rates of affective disorders compared to the Singapore national prevalence rate of 12%., Materials and Methods: In this cross-sectional study, 47 families were recruited from affective disorders and community-based psychiatry programmes run by a tertiary child psychiatry clinic. All children had a confirmed primary clinical diagnosis of depression or an anxiety disorder. Parents completed the Mini International Neuropsychiatric Interview (MINI) to assess for lifetime mood and anxiety disorders. They also completed the Adult Self Report (ASR) and Adult Behavior Checklist (ABCL) to assess current internalising and externalising symptoms., Results: Consistent with our hypothesis, 38.5% of mothers and 10.5% of fathers reported a lifetime mood and anxiety disorder. Nearly 1/3 of mothers had clinical/subclinical scores on current internalising and externalising problems. A similar pattern was found for internalising problems among fathers, with a slightly lower rate of clinical/subclinical externalising problems., Conclusion: Our findings are consistent with previous overseas studies showing elevated rates of affective disorders among parents - particularly mothers - of children seeking outpatient psychiatric care. Routine screening in this population may help to close the current treatment gap for adults with mood and anxiety disorders.

Background: Skin physiology measurement is receiving more attention for detecting vasculopathy in systemic sclerosis (SSc). Laser Doppler flowmetry (LDF) is a widely used physiological measurement to assess cutaneous microcirculation. However, findings of LDF may be subtle during early stage of microangiopathy in SSc., Objective: We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc., Methods: A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger's disease, the diagnosis of SSc was made according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results., Results: Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion., Conclusions: In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow.

We used a suture-and-open technique with a biatrial incision for primary sutureless repair of total anomalous pulmonary venous connection (TAPVC). With this technique, the common pulmonary venous sinus and its branching pulmonary veins are opened after completion of suturing of the left atrial incision to the pericardium around the common pulmonary venous sinus and its branching veins. The technique allows the primary sutureless repair of TAPVC to be done in a less bloody field under full-flow cardiopulmonary bypass. We have performed this technique in our recent 5 consecutive TAPVC patients without significant complications., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The increasing focus of healthcare systems worldwide on long-term care highlights the need for culturally sensitive Health-Related Quality of Life instruments to accurately capture perceived health of various populations. Such instruments require a contextualized conceptual framework of health domains, which is lacking in some socio-cultural contexts. We developed a comprehensive and culturally sensitive conceptual framework of health domains relevant to the Singaporean population. We recruited Singaporeans/ permanent residents, English/ Chinese-speaking, with/ without chronic illnesses to participate in focus group discussions (FGDs) and in-depth interviews (IDIs). We elicited health areas participants perceived to be important for them to be happy and satisfied with life. To encourage spontaneous emergence of themes, we did not specify any aspect beyond the broad domains of Physical, Mental, and Social health so as not to limit the emergence of new themes. Themes from the transcripts were distilled through open coding (two independent coders), then classified into more abstract domains (each transcript coded independently by two coders from a pool of six coders). From October 2013 to August 2014, 121 members of the general public participated in 18 FGDs and 13 IDIs (44.6% males, mean age: 53.3 years 77% Chinese, 9% Malay, 12% Indian, 63% with chronic illness) while 13 healthcare workers participated as patient-proxies in three FGDs. Thematic analysis identified 27 domains. The 15 physical domains included physical appearance, energy, physical fitness, and health and resistance to illness. The nine mental domains included emotions, self-esteem, and personal freedom. The three social domains were social contact, social relationships, and social roles. This conceptual framework reflected physical, mental, and social dimensions of well-being, suggesting that the Singapore population's views on health support the World Health Organization's definition of health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity"., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We adopted an operative technique of pulmonary valve (PV) annular enlargement with valve repair in tetralogy of Fallot (TOF) correction to reduce postoperative pulmonary regurgitation (PR) 16 years ago. Here, we have evaluated the long-term results., Methods: Between April 2000 and August 2005, 43 patients (26 men) with tetralogy of Fallot with pulmonary stenosis underwent PV annular enlargement with valve repair. The median age and body weight at the time of surgery were 14 months and 10.2 kg, respectively., Results: There was no operative mortality. Mean postoperative PR grade at discharge was 0.93 ± 0.40 (none or trivial in 10 patients, mild in 27 patients, mild to moderate in 5 patients and moderate in 1 patient), and the mean postoperative pressure gradient across PV was 13.0 ± 10.9 mmHg. The mean follow-up duration was 131.9 ± 42.9 months. During follow-up, 1 reoperation was performed for residual ventricular septal defect. The mean PR grade at the last follow-up echocardiography was 1.59 ± 0.60 (mild in 17 patients, mild to moderate in 8 patients, moderate in 14 patients, moderate to severe in 1 patient and severe in 3 patients), and the mean pressure gradient was 22.7 ± 9.9 mmHg. We have compared the incidence of moderate or more PR with the incidence of patients who underwent simple transannular patch enlargement through propensity score matching. The PV repair group had a lower incidence of moderate or more PR compared with the simple transannular patch group (40% vs 68%, P = 0.04)., Conclusions: PV annular enlargement with valve repair has reasonable long-term results and yields a lower long-term incidence of significant PR compared with the simple transannular patch enlargement technique.

The present study examined 1) the accuracy of two self-report measures for detecting panic-related anxiety in emergency department (ED) patients with cardiopulmonary complaints; and 2) whether modified scoring resulted in improved performance. English-speaking adults presenting to the ED of a large public hospital with palpitations, chest pain, dizziness, or difficulty breathing were evaluated for the presence of panic-related anxiety with the Structured Clinical Interview for DSM-IV (SCID) over a one-year period. Patients completed the panic disorder modules of the Patient Health Questionnaire (PHQ-PD) and Psychiatric Diagnostic Screening Questionnaire (PDSQ-PD). Sensitivity, specificity, area under the curve (AUC), and predictive values were compared for various cut-offs and scoring algorithms using SCID diagnosis of panic attacks (in the absence of panic disorder) or panic disorder as the reference standard. In this sample of 200 participants, the majority had a chief complaint of chest pain and 46.5% met SCID criteria for panic-related anxiety. The PDSQ-PD demonstrated only fair operating characteristics for panic attacks (AUC = 0.57) and good operating characteristics for panic disorder (AUC = 0.79). The PHQ-PD achieved adequate operating characteristics (AUC = 0.66) for panic attacks and good operating characteristics for panic disorder (AUC = 0.76) using a modified scoring algorithm or a single screening question (AUC = 0.72)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Sexual dysfunction occurs commonly in patients with psychiatric illness and may be related to the primary mental disorder, comorbidity with sexual disorders or medical illness, or medications used for mental disorders treatment, but the magnitude of this problem is unknown., Aim: To estimate the prevalence of current sexual activity, sexual dysfunction, and sexual attitude and influence of factors on patients with schizophrenia., Methods: This study used a cross-sectional design with a total of 317 patients diagnosed with schizophrenia. The subjects completed a demographic questionnaire, sexual attitude scale, sexual dysfunction scale, and sexual behavior scale. Descriptive analysis, difference analysis, and logistic regression model were used to identify relevant variables that may affect sexual life quality., Outcomes: Age, sexual satisfaction, and patient symptoms may predict sexual life quality on patients with schizophrenia., Results: The mean age of patients was 47.71 ± 9.54 years old. About the sexual activities, 53% of subjects had sexual intercourse experience, and 41.3% reported currently having sexual intercourse. The mean ± SD age for first sexual intercourse was 20.83 ± 5.95 years old (median was 20.0 years old). Moreover, women older than 50 years had significantly higher medians for the Brief Psychiatric Rating Scale (BPRS) score, higher proportions of sexual dysfunction, and lower proportions of feeling important to sexual life quality than men. For participants with age ≤50 years old, there was a significant relationship among BPRS group (mean score >2.5 vs ≤2.5), sexual dysfunction (P < .001), sexual life quality (P < .001), and sexual satisfaction (P = .006). Among the predictors of feeling important to sexual life quality, sexual satisfaction (odds ratio = 7.005, 95% CI = 4.126-11.892, P < .001) and BPRS score (odds ratio = 4.501, 95% CI = 2.042-9.923, P < .001) were significant independent factors after adding the interaction of age group and BPRS group., Clinical Translation: This study also reveals the close relationship between sexual satisfaction and BPRS score, which may predict sexual life quality of patients with schizophrenia. Limitations include the possibility of underreporting and bias associated with self-report measurement., Conclusion: Sexual life quality and sexual dysfunction on patients with schizophrenia are associated with interaction among psychological, sociological, and biochemical-pharmacological factors. Ma M-C, Chao J-K, Hung J-Y, et al. Sexual Activity, Sexual Dysfunction, and Sexual Life Quality Among Psychiatric Hospital Inpatients With Schizophrenia. J Sex Med 2018;15:324-333., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Subcritical water (SCW) extract of blue mussel was prepared at 100, 200, and 300 °C for 10, 30, and 60 min, respectively, and its effect on the activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, angiotensin-converting enzyme (ACE), and acetylcholinesterase (AChE) was evaluated. We found that DPPH radical scavenging, ACE inhibitory, and AChE inhibitory activities significantly increased with increasing extraction temperature and duration. For example, AChE inhibitory activity of the extract at 300 °C for 60 min increased to 63.1 ± 0.3%, while that at 100 °C for 10 min was 5.6 ± 0.3%. The results suggested that SCW extraction is attractive processing methods for obtaining high valued extract from blue mussel., Competing Interests: Compliance with ethical standardsThe authors declare no conflict of interest.

Objectives: Patients with panic-related anxiety often initially present to the emergency department (ED) complaining of respiratory or cardiac symptoms, but rates of detection of panic symptoms by ED physicians remain low. This study was undertaken to evaluate the relevance of panic attacks and panic disorder in ED patients who present with cardiopulmonary symptoms and to determine whether a brief symptom-based tool could be constructed to assist in rapid recognition of panic-related anxiety in the ED setting., Materials and Methods: English-speaking adult ED patients with a chief complaint of palpitations, chest pain, dizziness, or difficulty breathing were evaluated for the presence of panic attacks and panic disorder with the Structured Clinical Interview for DSM-IV Axis I Disorders. Participants completed self-report measures to assess panic-related symptoms, comorbid psychiatric conditions, health-related disability, and health service use., Results: In this sample (N=200), 23.5% had panic attacks and 23.0% had panic disorder. Both groups reported higher rates of panic attack symptoms, greater psychiatric comorbidity, greater health-related disability, and higher rates of ED and mental health service use compared with those without either condition. A brief 7-item tool consisting of panic symptoms identified patients with panic attacks or panic disorder with 85% accuracy (area under the curve=0.90, sensitivity=82%, specificity=88%)., Conclusions: Patients with panic attacks or panic disorder commonly present to the ED, but often go unrecognized. A brief 7-item clinician rating scale accurately identifies these patients among those ED patients presenting with cardiopulmonary complaints.

Background and Aim to Read: We report the results of a bicuspid expanded polytetrafluoroethylene (ePTFE) valved conduit used for right ventricular outflow tract reconstruction (RVOTR)., Methods: Between November 2005 and February 2009, 12 conduits were used for RVOTR. The mean age and weight of patients were 43.5 ± 46.4 months and 13.4 ± 8.6 kg. The main diagnosis was tetralogy of Fallot with pulmonary atresia in eight patients. The most common conduit size was 18 mm. The mean follow-up was 88.0 ± 35.9 months., Results: There were no operative and late mortalities. At discharge, the mean peak systolic pressure gradient across the RVOT was 14.1 ± 11.3 mmHg. There was no conduit valve regurgitation in nine patients. At the latest echocardiography (mean follow-up: 84.3 ± 35.5 months), the mean peak systolic pressure gradient across the RVOT was 59.7 ± 20.2 mmHg, and there was no conduit valve regurgitation in six patients. Freedom from conduit malfunction was 100% and 83.3%, at 1 and 8 years, respectively. Two conduits were explanted due to sternal compression and four from conduit malfunction. Freedom from explantation was 83.3% and 74.2% at 2 and 8 years, respectively., Conclusions: ePTFE bicuspid valved conduit has good late function in terms of valve regurgitation, but the pressure gradient across the conduit increases with time, which is the main cause of conduit failure and explantation., (© 2018 Wiley Periodicals, Inc.)

Aims and Objectives: To evaluate the effectiveness of a psychoeducational programme in enhancing motivation to change alcohol-addictive behaviour., Background: The prevalence of alcohol abuse has increased over the past 10 years, and the age of initial alcohol use has decreased gradually in Taiwan. Alcohol dependence is one of the leading causes of disability and has led to increases in the incidence of crime and violence, with alcohol abuse identified as a problem in society., Design: A quasi-experimental design with nonequivalent pre/post-testing was used., Methods: Alcohol-dependent inpatients undergoing alcohol treatment were selected from the psychiatric ward of a teaching hospital in northern Taiwan. The effectiveness of the psychoeducational programme in enhancing motivation to change alcohol-addictive behaviour was evaluated with the Severity of Alcohol Dependence Data Questionnaire and the Stages of Change Readiness and Treatment Eagerness Scale. In total, 24 and 51 participants were recruited to the experimental and control groups, respectively, for the baseline survey, and 14 and 17 were in the final survey, respectively., Results: After adjustment for baseline survey scores, the experimental group showed significantly greater increases in recognition and ambivalence relative to those observed in the control group., Conclusions: The results not only showed that the psychoeducational programme was effective in reinforcing addicted inpatients' motivation for changing their drinking behaviour but also provided clinical nurses with practical methods via which to enhance patient motivation., Relevance to Clinical Practice: The psychoeducational programme could assist clinical nurses in helping alcohol-dependent patients to recognise the nature of their problematic drinking; increase participants' ambivalence towards their drinking behaviour, leading to the contemplation of change; and strengthen the possibility that they will change their addictive behaviour., (© 2017 John Wiley & Sons Ltd.)

Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More recently, studies have shown that psoriasis is a systemic inflammatory disorder which can be associated with various comorbidities. In particular, psoriasis is associated with an increased risk of developing severe vascular events such as myocardial infarction and stroke. In addition, the prevalence rates of cardiovascular risk factors are increased, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. Consequently, mortality rates have been found to be increased and life expectancy decreased in patients with psoriasis, as compared to the general population. Various studies have also shown that systemic treatments for psoriasis, including methotrexate and tumor necrosis factor-α inhibitors, may significantly decrease cardiovascular risk. Mechanistically, the presence of common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability may explain the association between psoriasis and cardiometabolic disorders. In this article, we review the evidence regarding the association between psoriasis and cardiovascular comorbidities, focusing on severe vascular events, cardiovascular risk factors and implications for treatment., Competing Interests: The authors declare no conflict of interest.

Objective: The β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a β-nitrostyrene derivative CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene) was synthesized, and its anticancer activity on cervical cancer cells and the mechanisms involved were investigated., Methods: The effect of CYT-Rx20 on human cervical cancer cell growth was evaluated using cell viability assay. Reactive oxygen species (ROS) generation and annexin V staining were detected by flow cytometry. The protein expression levels of cleaved caspase-3, cleaved caspase-9, cleaved poly (ADPribose) polymerase, γH2AX, β-catenin, Vimentin, and Twist were measured by Western blotting. DNA double-strand breaks were determined by γ-H2AX foci formation and neutral comet assay. Migration assay was used to determine cancer cell migration. Nude mice xenograft was used to investigate the antitumor effects of CYT-Rx20 in vivo., Results: CYT-Rx20 induced cytotoxicity in cervical cancer cells by promoting cell apoptosis via ROS generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation, and DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited cervical cancer cell migration by regulating the expression of epithelial-to-mesenchymal transition markers. In nude mice, CYT-Rx20 inhibited cervical tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of mesenchymal markers β-catenin and Twist., Conclusions: CYT-Rx20 inhibits cervical cancer cells in vitro and in vivo and has the potential to be further developed into an anti-cervical cancer drug clinically., Competing Interests: The authors declare that there are no conflicts of interest., (© 2017 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.)

Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence., Methods: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test., Results: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively)., Conclusions: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidence-of-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: The β-nitrostyrene family has been previously reported to possess anticancer property. However, the biological effects of β-nitrostyrenes on ovarian cancer and the underlying mechanisms involved remain unclear. In the present study, we synthesized a β-nitrostyrene derivative, CYT-Rx20 3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene), and investigated its anticancer effects and the putative pathways of action in ovarian cancer., Methods: The effects of CYT-Rx20 were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, FACS analysis, annexin V staining, immunostaining, comet assay, immunoblotting, soft agar assay, migration assay, nude mice xenograft study and immunohistochemistry., Results: CYT-Rx20 induced cytotoxicity in ovarian cancer cells by promoting cell apoptosis via ROS generation and DNA damage. CYT-Rx20-induced cell apoptosis, ROS generation and DNA damage were reversed by thiol antioxidants. In addition, CYT-Rx20 inhibited ovarian cancer cell migration by regulating the expression of epithelial to mesenchymal transition (EMT) markers. In nude mice, CYT-Rx20 inhibited ovarian tumor growth accompanied by increased expression of DNA damage marker γH2AX and decreased expression of EMT marker Vimentin., Conclusions: CYT-Rx20 inhibits ovarian cancer cells in vitro and in vivo, and has the potential to be further developed into an anti-ovarian cancer drug clinically.

Background: The β-nitrostyrene family possesses anticancer properties. In this study, β-nitrostyrene derivative CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene) was synthesized and investigated its anticancer activity in oral cancer., Methods: Anticancer activity of CYT-Rx20 and the underlying mechanisms were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, fluorescence-activated cell sorter analysis, annexin V staining, comet assay, glutathione (GSH)/glutathione disulfide (GSSG) ratio, immunoblotting, soft agar assay, nude mice xenograft study, and immunohistochemistry., Results: CYT-Rx20-induced cell apoptosis via ROS generation and mitochondrial membrane potential reduction, associated with release of mitochondrial cytochrome C to cytosol and activation of downstream caspases and poly ADP-ribose polymerase (PARP). Furthermore, CYT-Rx20 induced mitochondrial ROS accumulation and mitochondrial dysfunction, followed by GSH downregulation. CYT-Rx20-induced cell apoptosis, ROS generation, and DNA damage were reversed by thiol antioxidants. In nude mice, CYT-Rx20 inhibited oral tumor growth accompanied by increased expression of γH2AX, GSH reductase, and cleaved-caspase-3., Conclusion: CYT-Rx20 has the potential to be further developed into an antioral cancer drug clinically. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1055-1064, 2017., (© 2017 Wiley Periodicals, Inc.)