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Ruifeng Bai,1 Jianqiu Pei,1 Shengqiang Pei,1 Xiangfeng Cong,1 Jerold Chun,2 Fang Wang,1,3,4 Xi Chen1,3 1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Neuroscience Drug Discovery, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; 3Diagnostic Laboratory Service, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of ChinaCorrespondence: Xi Chen; Fang Wang, Email chenxifw@pumc.edu.cn; fray.163@163.comBackground: Increased endothelial permeability of pulmonary vessels is a primary pathological characteristic of septic acute lung injury (ALI). Previously, elevated lysophosphatidic acid (LPA) levels and LPA2 (an LPA receptor) expression have been found in the peripheral blood and lungs of septic mice, respectively. However, the specific role of LPA2 in septic ALI remains unclear.Methods: A lipopolysaccharide (LPS)-induced model of sepsis was established in wild-type (WT) and global LPA2 knockout (Lpar2−/−) mice. We examined mortality, lung injury, assessed endothelial permeability through Evans blue dye (EBD) assay in vivo, and transendothelial electrical resistance (TEER) of mouse lung microvascular endothelial cells (MLMECs) in vitro. Enzyme-linked immunosorbent assay (ELISA), histopathological, immunofluorescence, immunohistochemistry, and Western blot were employed to investigate the role of LPA2 in septic ALI.Results: Lpar2 deficiency increased vascular endothelial permeability, impaired lung injury, and increased mortality. Histological examination revealed aggravated inflammation, edema, hemorrhage and alveolar septal thickening in the lungs of septic Lpar2−/− mice. In vitro, loss of Lpar2 resulted in increased permeability of MLMECs. Pharmacological activation of LPA2 by the agonist DBIBB led to significantly reduced inflammation, edema and hemorrhage, as well as increased expression of the vascular endothelial tight junction (TJ) protein zonula occludens-1 (ZO-1) and claudin-5, as well as the adheren junction (AJ) protein VE-cadherin. Moreover, DBIBB treatment was found to alleviate mortality by protecting against vascular endothelial permeability. Mechanistically, we demonstrated that vascular endothelial permeability was alleviated through LPA-LPA2 signaling via the PLC-PKC-FAK pathway.Conclusion: These data provide a novel mechanism of endothelial barrier protection via PLC-PKC-FAK pathway and suggest that LPA2 may contribute to the therapeutic effects of septic ALI.Keywords: septic ALI, LPA, vascular endothelial permeability, LPA2, lung microvascular endothelial cells

Yuan Cao,1– 3 Yulin Li,1– 3 Wenqiang Han,1– 3 Xu Jia,1– 3 Ping Zhu,1– 3 Bin Wei,4 Xiaoyan Cong,5,6 Zhihao Wang7,8 1Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 2State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 4Shandong Asia-Pacific Highvarve Organisms Science and Technology Co, Ltd, Jinan, People’s Republic of China; 5Institute of Animal Science and Veterinary Medicine, Shandong Key Laboratory of Animal Disease Control and Breeding, Shandong Academy of Agricultural Sciences, Jinan, People’s Republic of China; 6Jinan Kuoda Biotechnology Co, Ltd, Jinan, People’s Republic of China; 7Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 8Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Xiaoyan Cong; Zhihao Wang, Email xycong@163.com; wangzhihaosdu@126.comPurpose: Sarcopenia has been described as a new complication of type 2 diabetes mellitus (T2DM). T2DM and sarcopenia impact each other, resulting in a variety of adverse outcomes such as frailty, disability, poor quality of life and increased mortality. Sodium butyrate (NaB) is reported to play a protective role against T2DM. The present study aimed to investigate whether NaB could ameliorate T2DM-related sarcopenia and the underlying mechanisms.Materials and Methods: The male db/db mice at 7-weeks were used as T2DM-related sarcopenia animal model with C57BL/6J mice as control. Mice were grouped according to whether they received NaB orally as follows: C57BL/6J+water group, C57BL/6J+NaB group, db/db+water group, and db/db+NaB group. Then, db/db mice receiving NaB orally were administered with inhibitors of group 2 innate lymphocytes (ILC2s), anti-CD90.2 by intraperitoneal injection divided into db/db+NaB+PBS group and db/db+NaB+anti-CD90.2 group. NaB dissolved in water at 150 mM. The skeletal muscle mass was measured by dural X-ray (DXA) test. ILC2s in spleen and skeletal muscle were evaluated by flow cytometry. The expressions of IL-33, IL-13, STAT3, P-STAT3, GATA-3 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) were assessed by ELISA or WB. The morphology of skeletal muscle fibers was assessed by immunofluorescence staining.Results: The proportion of ILC2s and the expressions of ILC2s markers IL-13 and GATA-3 were all significantly decreased in db/db mice, and these changes were improved by NaB. NaB increased the proportion of slow-twitch fibers in gastrocnemius, thus partially reversing the reduced exercise capacity of db/db mice. The expression of slow-twitch fibers marker PGC-1α induced by NaB was increased via activation of ILC2s/IL-13/STAT3 pathway. On the other way, IL-33 was not necessary for the activation of ILC2s/IL-13/STAT3 pathway. After depletion of ILC2s by anti-CD90.2, the ameliorating effect of NaB on T2DM-related sarcopenia was partially antagonized.Conclusion: These results indicated that NaB could ameliorate type 2 diabetes-related sarcopenia by activating IL-33-independent ILC2s/IL-13/STAT3 signaling pathway.Keywords: diabetes mellitus, sarcopenia, ILC2s, sodium butyrate, IL-13

Zhiguang Fan,1,2 Xiangxin Cong,1 Min Tao,1 Shijia Wu,3 Peng Gao3 1Department of Education, Jilin International Studies University, Changchun City, Jilin Province, People’s Republic of China; 2Department of Marxism, Changchun University of Chinese Medicine, Changchun City, Jilin Province, People’s Republic of China; 3Department of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun City, Jilin Province, People’s Republic of ChinaCorrespondence: Peng Gao, Department of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Boshuo Street 1035, Changchun City, Jilin Province, 130117, People’s Republic of China, Tel +86-431-84924101, Fax +86 1 594-831-4623, Email gaopengcc@126.comBackground/Objective: Internalized occupational stigma may develop in physicians as a result of their identification with the public negative labels and stereotypes about them, and then internalization of them as a part of their self-concept. This study aims to develop the Physician Internalized Occupational Stigma Scale (PIOSS) and to examine its reliability and validity.Methods: In study 1, the initial scale was used to investigate 356 physicians. While in study 2, a total of 346 physicians were investigated with the survey tools named the PIOSS, the Career Commitment Scale (CCS), the Workplace Well-Being Scale (WWBS), the Scale for the Doctor with Patient-doctor Relationship (DDPRQ-10), the Intent to Leave Scale (ILS) and the Occupational Disidentification Scale (ODS).Results: The PIOSS includes 19 items divided into 3 dimensions: label identification, status loss, and career denial. The results of confirmatory factor analysis (CFA) reveal that the three-factor model fitted well (χ2/df=2.574, RMSEA= 0.068, CFI= 0.931, IFI= 0.931, TLI= 0.919, PNFI= 0.762, PCFI= 0.795). The PIOSS total and each dimension scores were significantly negatively correlated with the CCS and the WWBS scores and remarkably positively associated with the DDPRQ-10, the ILS, and the ODS scores. Cronbach’s α coefficients for the PIOSS total scale and dimensions ranged from 0.775 to 0.914, and split-half reliability coefficients ranged from 0.801 to 0.931. In addition, the PIOSS exhibited cross-gender invariance.Conclusion: Having good reliability and validity, the PIOSS can serve as a valid tool for the assessment of physician internalized occupational stigma.Keywords: physician, internalized occupational stigma, reliability, validity

Wei Li,1 Xiangxin Cong,1 Zhiguang Fan,1 Fei Li2 1Department of Education, Jilin International Studies University, Changchun, People’s Republic of China; 2Department of Marxism, Changchun University of Chinese Medicine, Changchun, People’s Republic of ChinaCorrespondence: Zhiguang Fan, Department of Education, Jilin International Studies University, 3658 Jingyue Street, Changchun City, Jilin Province, 130117, People’s Republic of China, Tel +86-0431-84924101, Fax +86 1 594-831-4623, Email fanyqm@126.comIntroduction: Moderate emotion reactivity in the face of daily stress is of positive significance regarding individuals’ psychological well-being and environmental adaptation. The study on intergenerational transmission of Dark Triad and emotion reactivity has confirmed the existence of higher levels of Dark Triad and emotion reactivity in college students in the Chinese sample, which may provide a reference for future related studies.Purpose: The study examined the intergenerational transmission effects of Dark Triad and Emotion Reactivity in families. And based on this, it further analyzed the mediating role of parental emotion reactivity and children’s Dark Triad in the influence of parental Dark Triad on children’s emotion reactivity.Methods: The questionnaire was administered to 486 families inclusive of fathers, mothers, and children utilizing the Emotion Reactivity Scale (ERS) and the Dirty Dozen (DD).Results: 1) The intergenerational transmission was presented in the three Dark Triad traits and emotion reactivity. 2) The level of Dark Triad and emotion reactivity of children was remarkably higher than that of their parents. 3) The Dark Triad scores of males were considerably higher than those of females, while there were no significant differences in the scores of emotion reactivity between them. 4) The actor and partner effects of Dark Triad and emotion reactivity between father and mother were established. 5) Parental emotion reactivity and children’s Dark Triad exerted mediating effects on the impact of parental Dark Triad on children’s emotion reactivity.Conclusion: The effect of parental three Dark Triad on their children’s emotion reactivity as well as its mediation mechanism were examined respectively by the present study in the light of APIM and intergenerational transmission analysis. It was concluded that the findings carried both theoretical and reference value for developing moderate emotion reactive ability toward college students.Keywords: Dark Triad, emotion reactivity, intergenerational transmission, APIM, mediating effect

Xuzichun Wang, Jiaqi Leng, Xiangxin Cong, Zhiguang Fan School of Education, Jilin International Studies University, Changchun, People’s Republic of ChinaCorrespondence: Zhiguang Fan, School of Education, Jilin International Studies University, Jingyue Street 3658, Changchun, Jilin, People’s Republic of China, Tel +86 1594-831-4623, Fax +86 431-84924101, Email fanyqm@126.comBackground and Aim: It is particularly obvious that vocational and technical education (VTE) has been stigmatized for a long time in the field of secondary vocational education. The severe stigma that secondary vocational students suffer from may negatively affect junior high school students’ choice to attend secondary vocational schools and become such students. This study aims to develop the junior high school students to Secondary Vocational Students Stigma Scale (SVSSS) and to test its reliability and validity.Methods: The initial questionnaire was formed following an open-ended questionnaire and expert review based on the conceptual model of stigma as a theoretical framework. A total of 316 junior high school students (sample 1) were administered with the resulting data subjected to item analysis and exploratory factor analysis (EFA). And a total of 416 junior high school students (sample 2) were administered with the data applied for validity, reliability, and cross-group invariance test.Results: It was revealed in the EFA that the SVSSS consists of 20 items in total, including three dimensions, namely negative labeling, social isolation, and devaluation and discrimination. Favorable structural validity of the questionnaire was demonstrated in confirmatory factor analysis (CFA) (x2/df=2.907, RMSEA=0.068, RFI=0.925, CFI=0.956, NFI=0.934, IFI=0.956, PNFI=0.816, PCFI=0.835). The aggregate scores of the SVSSS, exhibiting cross-gender invariance, were significantly negatively associated with willingness to choose secondary vocational education and positively correlated with academic performance. Cronbach’s α coefficient of the SVSSS and each dimension ranged from 0.815 to 0.963, with split-half reliability from 0.777 to 0.969.Conclusion: Featuring favorable reliability and validity, the SVSSS was found to be an effective tool for the measurement of the secondary vocational education stigma among junior high school students, with its measurement invariance across genders.Keywords: junior high school students, secondary vocational students, stigma, reliability, validity

Xilin Liu,1,* Hong Li,2,* Xianling Cong,3 Da Huo,1 Lele Cong,4 Guangzhi Wu1 1Department of Hand Surgery, China Japan Union Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China; 2Emergency Medical Department, China Japan Union Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China; 3Tissue Bank, China Japan Union Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China; 4Department of Dermatology, China Japan Union Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangzhi WuDepartment of Hand Surgery, China Japan Union Hospital of Jilin University, Changchun City, Jilin Province 130033, People’s Republic of ChinaTel +86-13944181019Email wuguangzhi@jlu.edu.cnBackground/Objective: The immunotoxin α-MSH-PE38KDEL consisting of α-MSH and PE38KDEL showed high cytotoxicity on MSH receptor-positive melanoma cells, suggesting that α-MSH-PE38KDEL might be a potent drug for the treatment of melanoma. Herein, we explored whether the Erk1/2/MITF/TYR signaling, a verified target of α-MSH/MC1R, was involved in α-MSH-PE38KDEL-mediated cytotoxicity.Methods: Human melanoma cell line A375, mouse melanoma cell line B16-F10, human breast cancer cell line MDA-MB-231 and human primary epidermal melanocytes (HEMa) with different expression levels of MC1R were used in this study. Cell apoptosis and viability were determined by using flow cytometry and MTT assays. Protein expressions were tested by Western blotting.Results: The expression levels of MC1R in A375 and B16-F10 cells were significantly higher than that of MDA-MB-231 and HEMa. α-MSH-PE38KDEL treatment induced a significant inhibition in cell viability in A375 and B16-F10 cells, while showed no obvious influence in the viability of MDA-MB-231 and HEMa cells. However, knockdown of MC1R abolished α-MSH-PE38KDEL role in promoting cell apoptosis in A375 and B16-F10 cells, and upregulation of MC1R endowed α-MSH-PE38KDEL function to promote cell apoptosis in MDA-MB-231 and HEMa cells. Additionally, α-MSH-PE38KDEL treatment increased the phosphorylation levels of Erk1/2 and MITF (S73), and decreased MITF and TYR expressions in an MC1R-dependent manner. All of the treatments, including inhibition of Erk1/2 with PD98059, MC1R downregulation and MITF overexpression weakened the anti-tumor role of α-MSH-PE38KDEL in melanoma.Conclusion: Collectively, this study indicates that α-MSH-PE38KDEL promotes melanoma cell apoptosis via modulating Erk1/2/MITF/TYR signaling in an MC1R-dependent manner.Keywords: MC1R, melanoma, α-MSH-PE38KDEL, apoptosis, viability, Erk1/2/MITF/TYR

Qian Sun,1 Hongyan Sun,2 Lele Cong,1 Yang Zheng,1 Nan Wu,1 Xianling Cong1 1Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Xianling CongDepartment of Dermatology, China-Japan Union Hospital of Jilin University, Xiantai Road 126, Changchun, Jilin 130033, People’s Republic of ChinaTel +86-15904420533Fax + 86-431-89876626Email congxl@jlu.edu.cnAbstract: Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥ 5 years [pooled RR=1.18; 95% CI: 1.07– 1.31; I2=0%] and ≥ 10 years [pooled RR=1.25; 95% CI: 1.06– 1.48; I2=0%]). Women who first used OC 15– 19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03– 2.24; I2=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02– 1.24; I2=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17– 1.37; I2=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥ 20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.Keywords: oral contraceptives, hormone replacement therapy, menopause, menarche, parity

Jinran Li,1 Yuxi Jia,1 Peng Zhang,2 Huailin Yang,2 Xianling Cong,1 Lin An,3 Chunsheng Xiao2,4 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China; 3Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 4Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, People’s Republic of ChinaCorrespondence: Xianling Cong; Lin An Tel +86-431-89876626; +86-431-84995523Email congxl@jlu.edu.cn; anlin.changchun@163.comBackground: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL.Purpose: We proposed a facile “in situ drug conjugation-induced self-assembly” strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma.Methods: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model.Results: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL.Conclusion: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.Keywords: celastrol, self-assembly, self-stabilization, nanomedicine, melanoma

When a child shows signs of potential motor developmental disorders, early diagnosis of central nervous system (CNS) impairment is beneficial. Known as the first CNS-controlled mobility for most of infants, mobility during crawling usually has been used in clinical assessments to identify motor development disorders. The current clinical scales of motor development during crawling stage are relatively subjective. Objective and quantitative measures of infant crawling afford the possibilities to identify those infants who might benefit from early intervention, as well as the evaluation of intervention progress. Thus, increasing researchers have explored objective measurements of infant crawling in typical and atypical developing infants. However, there is a lack of comprehensive review on infant-crawling measurement and analysis toward bridging the gap between research crawling analysis and potential clinical applications. In this narrative review, we provide a practical overview of the most relevant measurements in human infant crawling, including acquisition techniques, data processing methods, features extraction, and the potential value in objective assessment of motor function in infancy; meanwhile, the possibilities to develop crawling training as early intervention to promote the locomotor function for infants with locomotor delays are also discussed.

Qian Sun,1 Hongyan Sun,2 Lele Cong,1 Yang Zheng,1 Nan Wu,1 Xianling Cong1 1Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Tissue Bank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Xianling Cong, Department of Dermatology, China-Japan Union Hospital of Jilin University, Xiantai Road 126, Changchun, Jilin, 130033, People’s Republic of China, Tel +86 15904420533, Fax +86 431-89876626, Email congxl@jlu.edu.cn View the original paper by Dr Sun and colleagues This is in response to the Letter to the Editor

Li Chen,1,* Ying Yan,2,* Lihua Zhu,3 Xiliang Cong,1 Sen Li,1 Shubin Song,1 Hongjiang Song,1 Yingwei Xue1 1Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Internal Oncology, Harbin The First Hospital, Harbin, Heilongjiang, 3Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China *These authors contributed equally to this work Background and objective: A novel systemic immune–inflammation index named SII (SII=N×P/L), which is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy.Subjects and methods: The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (

Shubin Song, Chunfeng Li, Sen Li, Xiliang Cong, Yingwei Xue Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China Background and objectives: Patients of different ages with gastric cancer (GC) have different clinicopathological features and prognoses. The results for different crowds are limited and controversial. The aim of this study was to investigate the differences in clinicopathological features and prognoses between younger and older GC patients.Methods: From January 2007 to December 2011, a consecutive total of 112 GC patients under 41 years old and 358 GC patients over 69 years old who underwent gastrectomy for GC were recruited for this study. Then, the clinicopathological features and prognoses of these patients were analyzed comparatively. Results: The gender, differentiation, carbohydrate antigen (CA) 19–9 and carcinoembryonic antigen (CEA) were significantly different between younger and older GC patients. There were more female and undifferentiated younger GC patients, and there were higher percentages of positive CA19–9 and CEA in older GC patients. The number of metastatic lymph nodes was an independent risk parameter for prognosis in younger patients, and the AJCC TNM (Tumor-Nodes-Metastases classification by American Joint Committee on Cancer) stage, radicality and tumor size were independent risk parameters for prognosis in older GC patients. Younger GC patients have a much better prognoses with lower monocyte-to-lymphocyte ratio and higher prognostic nutritional index than older patients. Conclusions: Younger GC patients have better immunity and nutritional status and better prognoses. The number of metastatic lymph nodes was the only risk parameter for prognosis in younger GC patients. We should take more effective treatments for younger GC patients with lymph nodes metastasis and pay more attention to the nutritional problems of older GC patients. Keywords: gastric cancer, clinicopathological feature, age, prognosis

BackgroundThe increasing usage of statins (the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) has revealed a number of unexpected beneficial effects, including a reduction in cancer risk.MethodsWe investigated the direct anticancer effects of different statins approved for clinical use on human breast and brain cancer cells. We also explored the effects of statins on cancer cells using in silico simulations.ResultsIn vitro studies showed that cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines. Consistently, pitavastatin was more effective than fluvastatin in inhibiting U87 tumour growth in vivo. Intraperitoneal injection was much better than oral administration in delaying glioblastoma growth. Following statin treatment, tumour cells were rescued by adding mevalonate and geranylgeranyl pyrophosphate. Knockdown of geranylgeranyl pyrophosphate synthetase-1 also induced strong cell autophagy and cell death in vitro and reduced U87 tumour growth in vivo. These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells.ConclusionsOur study demonstrates the potent anticancer effects of statins. These safe and well-tolerated drugs need to be further investigated as cancer chemotherapeutics in comprehensive clinical studies.

Let d (x , y) denote the length of a shortest path between vertices x and y in a graph G with vertex set V. For a positive integer k , let d k (x , y) = min { d (x , y) , k + 1 } and R k { x , y } = { z ∈ V : d k (x , z) ≠ d k (y , z) }. A set S ⊆ V is a distance-k resolving set of G if S ∩ R k { x , y } ≠ ∅ for distinct x , y ∈ V. In this paper, we study the maker-breaker distance- k resolving game (MB k RG) played on a graph G by two players, Maker and Breaker, who alternately select a vertex of G not yet chosen. Maker wins by selecting vertices which form a distance- k resolving set of G , whereas Breaker wins by preventing Maker from winning. We denote by O R , k (G) the outcome of MB k RG. Let ℳ , ℬ and , respectively, denote the outcome for which Maker, Breaker, and the first player has a winning strategy in MB k RG. Given a graph G , the parameter O R , k (G) is a non-decreasing function of k with codomain { − 1 = ℬ , 0 = , 1 = ℳ }. We exhibit pairs G and k such that the ordered pair (O R , k (G) , O R , k + 1 (G)) realizes each member of the set { (ℬ ,) , (ℬ , ℳ) , (, ℳ) } ; we provide graphs G such that O R , 1 (G) = ℬ , O R , 2 (G) = and O R , k (G) = ℳ for k ≥ 3. Moreover, we obtain some general results on MB k RG and study the MB k RG played on some graph classes. [ABSTRACT FROM AUTHOR]

Tight junction proteins play a crucial role in paracellular transport in salivary gland epithelia. It is clear that severe xerostomia in patients with HELIX syndrome is caused by mutations in the claudin-10 gene. However, little is known about the expression pattern and role of claudin-10 in saliva secretion in physical and disease conditions. In the present study, we found that only claudin-10b transcript was expressed in human and mouse submandibular gland (SMG) tissues, and claudin-10 protein was dominantly distributed at the apicolateral membranes of acini in human, rat, and mouse SMGs. Overexpression of claudin-10 significantly reduced transepithelial electrical resistance and increased paracellular transport of dextran and Na+ in SMG-C6 cells. In C57BL/6 mice, pilocarpine stimulation promoted secretion and cation concentration in saliva in a dose-dependent increase. Assembly of claudin-10 to the most apicolateral portions in acini of SMGs was observed in the lower pilocarpine (1 mg/kg)–treated group, and this phenomenon was much obvious in the higher pilocarpine (10 mg/kg)–treated group. Furthermore, 7-, 14-, and 21-wk-old nonobese diabetic (NOD) and BALB/c mice were used to mimic the progression of hyposalivation in Sjögren syndrome. Intensity of claudin-10 protein was obviously lower in SMGs of 14- and 21-wk-old NOD mice compared with that of age-matched BALB/c mice. In the cultured mouse SMG tissues, interferon-γ (IFN-γ) downregulated claudin-10 expression. In claudin-10–overexpressed SMG-C6 cells, paracellular permeability was decreased. Furthermore, IFN-γ stimulation increased p-STAT1 level, whereas pretreatment with JAK/STAT1 antagonist significantly alleviated the IFN-γ–induced claudin-10 downregulation. These results indicate that claudin-10 functions as a pore-forming component in acinar epithelia of SMGs, assembly of claudin-10 is required for saliva secretion, and downregulation of claudin-10 induces hyposecretion. These findings may provide new clues to novel therapeutic targets on hyposalivation. [ABSTRACT FROM AUTHOR]