Search

Xichen Wan,1– 3 Tong Lin,1– 3 Yunzhen Luo,4 Jiaxu Hong,1– 3,5 Jingyi Cheng,1– 3,&ast; Keqing Zhao6,&ast; 1Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2NHC Key Laboratory of Myopia and Related Eye Diseases, Shanghai, People’s Republic of China; 3Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Zhao, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email rhinoresearch@163.com Jingyi Cheng, Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email tippicjy@126.comPurpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis.Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer’s tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition.Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P> 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001).Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.Keywords: vidian neurectomy, ocular surface, dry eye

Hao Zhang,1,&ast; Anqi Xu,2,&ast; Xiangxiang Li,3,&ast; Binbin Pan,1 Xin Wan1 1Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Quality Management, Nanjing Red Cross Blood Center, Nanjing, People’s Republic of China; 3Department of Nephrology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Binbin Pan; Xin Wan, Department of Nephrology, Nanjing First Hospital, No. 68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Tel +86 025-87726209, Email panbinbin@njmu.edu.cn; wanxin@njmu.edu.cnBackground and Objectives: Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown.Design, Setting, Participants and Measurements: A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples t-test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria.Results: No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (r=0.255, p=0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196– 5.773, p< 0.01), gender (OR=1.737, 95% CI 1.116– 2.702, p=0.014), age (OR=0.983, 95% CI 0.969– 0.997, p=0.014), and history of diabetes (OR=0.405, 95% CI 0.235– 0.699, p< 0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75– 0.82, p< 0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735– 0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674.Conclusion: Complement C4/IgG could be used to predict macroproteinuria.Keywords: complement C4, immunoglobulin G, macroproteinuria, chronic kidney disease, kidney biopsy

Binbin Liu,1,&ast; Pan Su,1,&ast; Peilei Hu,1,&ast; Mi Yan,1 Wenbin Li,1 Songlin Yi,1 Zhenhua Chen,1 Xiaoping Zhang,1 Jingwei Guo,1 Xiaojie Wan,1 Jue Wang,1 Daofang Gong,1 Hua Bai,1 Kanglin Wan,2 Haican Liu,2 Guilian Li,2 Yunhong Tan1 1Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China; 2National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunhong Tan, Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China, Tel +86-13874947876, Email Tanyunhong@163.com Guilian Li, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China, Tel +86-18519886112, Email liguilian@icdc.cnBackground: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province.Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates.Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates.Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.Keywords: tuberculosis, pyrazinamide, transmission, pncA mutations, rpsA mutations, panD mutations, China

Xuan Yi,1 Xinxing Wan,1 Md Asaduzzaman Khan,2,3 Xiaoying Sun,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng4 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Research Division, Nature Study Society of Bangladesh, Dhaka, 1000, Bangladesh; 3Pulmonary Department, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, 02118, USA; 4Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis.Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR).Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs.Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.Keywords: circRNA microarray, subcutaneous adipose tissue, human adipose tissue-derived stromal cells, adipogenesis, SAT

Xuan Wan,1,&ast; Yuting Fang,2,&ast; Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoxi Cai; Hangming Dong, Email hxkc@smu.edu.cn; dhm@smu.edu.cnObjective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90α (eHSP90α) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90α. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo.Results: GW4869 inhibited the expression of eHSP90α, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90α, providing new strategies for enhancing gefitinib sensitivity in NSCLC.Keywords: GW4869, EMT, gefitinib-sensitive NSCLC, eHSP90&#x03B1

Xueqi Wan,&ast; Huan Zhang,&ast; Jinfan Tian,&ast; Peng Hao, Libo Liu, Yuquan Zhou, Jing Zhang, Xiantao Song, Changjiang Ge Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjiang Ge; Xiantao Song, Email cjge1116@163.com; song0929@mail.ccmu.edu.cnAbstract: Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.Keywords: ferroptosis, iron overload, oxidation, lipid peroxidation, atherosclerosis

Pan Luo,&ast; Qiling Yuan,&ast; Xianjie Wan, Mingyi Yang, Peng Xu Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Xu, Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shanxi, People’s Republic of China, Email sousou369@163.comAbstract: The pathological manifestations of osteoarthritis (OA) involve the destruction of articular cartilage, synovial sac thickening, subchondral osteosclerosis and osteophyte formation. The types of cells involved in OA include chondrocytes, osteoblasts, osteoclasts, synovial fibroblasts, T cells, macrophages, and mesenchymal stem cells (MSCs). There are many effects of immune cells in OA, and innate immune cells such as dendritic cells and macrophages have significant roles in the pathogenesis of OA. On the other hand, the role of adaptive immune cells such as T-cell subsets, B-cell subsets, and NK cells is important in OA pathogenesis. MSCs not only play a key role in the dynamic balance and repair of OA tissue but also inhibit the immune system. Therefore, MSCs are a new potential therapeutic agent for OA. This review mainly summarizes the effects of various immune cells and cytokines on different cells in OA to find new effective therapeutic targets for OA therapy based on the immune system and cytokine activity sites to prevent the development of OA.Keywords: osteoarthritis, immune cells, chondrocytes, mesenchymal stem cells, osteoblasts

Wenwen Sun,1,2 Yuling Xing,2 Fei Zhou,2,3 Yingao Ma,2,3 Xiaozheng Wan,2,4 Huijuan Ma3,5 1Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Huijuan Ma, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comObjective: In view of the high prevalence of osteoporosis in diabetic patients, this study aimed to investigate the correlation between TyG-BMI, which represents insulin resistance, and bone loss markers, which represent bone metabolism, in an attempt to provide new ideas for the early prevention and diagnosis of osteoporosis in patients with T2DM.Patients and Methods: A total of 1148 T2DM were enrolled. The clinical data and laboratory indicators of the patients were collected. TyG-BMI was calculated based on fasting blood glucose (FBG), triglycerides (TG), and body mass index (BMI) levels. Patients were divided into Q1-Q4 groups according to TyG-BMI quartiles. According to gender, two groups were divided into men and postmenopausal women. Subgroup analysis was performed according to age, course of disease, BMI, TG level and 25(OH)D3 level. The correlation between TyG-BMI and BTMs was investigated by correlation analysis and multiple linear regression analysis using SPSS25.0 statistical software.Results: 1. Compared with Q1 group, the proportion of OC, PINP and β-CTX in Q2, Q3 and Q4 groups decreased significantly. 2. Correlation analysis and multiple linear regression analysis showed that TYG-BMI was negatively correlated with OC, PINP and β-CTX in all patients and male patients. In postmenopausal women, TyG-BMI was negatively correlated with OC and β-CTX, but not with PINP. 3. Subgroup analysis of male patients and postmenopausal female patients according to age, course of disease, BMI, TG and 25(OH)D3 showed that TyG-BMI had a stronger negative correlation with BTMs in male patients with age < 65, disease duration < 10, BMI≥ 24, TG < 1.7, and 25(OH)D3≥ 20.Conclusion: This study was the first to show an inverse association between TyG-BMI and BTMs in T2DM patients, suggesting that high TyG-BMI may be associated with impaired bone turnover.Keywords: type 2 diabetes mellitus, triglyceride glucose-body mass index, bone turnover markers, inflammation

Xiaoying Sun,1 Xinxing Wan,1 Md Asaduzzaman Khan,2 Keke Zhang,1 Xuan Yi,1 Zhouqi Wang,1 Ke Chen1 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2The Research Centre for Preclinical Medicine, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Ke Chen, Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Brown adipose tissue (BAT) can rapidly generate heat and improve energy metabolism. Circular RNAs (circRNAs) are cellular endogenous non-coding RNAs, which can regulate the development and progress of different diseases. However, the role of circRNAs in human BAT is not fully understood. Here, we analyzed the differentially expressed circRNAs (DECs) in human BAT, as well as in white adipose tissue (WAT), and identified new biomarkers of BAT.Patients and Methods: Three human BAT and three human subcutaneous WAT samples were selected, and circRNA microarray was performed. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of six circRNAs. Finally, the functional analysis was performed by bioinformatics.Results: Compared to WAT, 152 upregulated circRNAs and 201 downregulated circRNAs were identified in BAT. The DECs were further subjected to GO and KEGG enrichment analysis. Several circRNAs, for example, hsa_circ_0006168, hsa_circ_26337 and hsa_circ_0007507 were found upregulated and hsa_circ_0030162 was found downregulated in human BAT compared to WAT.Conclusion: This study profiles the circRNA expression in human BAT and WAT, and suggests hsa_circ_0006168, hsa_circ_26337, hsa_circ_0007507, and hsa_circ_0030162 as novel biomarkers for human BAT.Keywords: brown adipose tissue, biomarkers, circRNA microarray

The suspension smelting oxidation step has favourable conditions to generate chemical flue dust from the low-boiling elements of the feed mixture due to the high particle temperatures in the reaction shaft where combusting sulphide mineral particles reach temperatures above the melting point of magnetite. Arsenic, antimony, lead, and zinc are common impurity elements of high volatility in copper concentrates. They tend to accumulate in the flue dust due to the high volatility and closed mode of the flue dust circulation practiced in most industrial smelting-converting processes. Then, the only outlets for the volatile impurities are the anodes and the discard slag. A separate flue dust treatment for impurity removal is an option but it creates an additional step for the smelting plant and cost in the processing. When the concentrate grades decrease, and their impurity levels rise this outlet for the trace elements may become necessary. The arsenic condensation mechanisms in dust-free conditions in the copper flash smelting process gas train have been recently studied in SO2-air-N2 gas mixtures. It seems that the formation mechanism of arsenic-containing dust deposits is kinetically constrained, and their chemistries are influenced by the condensation temperature and atmosphere.

Anqi Zhang,1,2,&ast; Jinsong Wang,1– 3,&ast; Xiaojuan Wan,2 Jing Zhang,3 Zihe Guo,3 Yamin Miao,2 Shuhan Zhao,2 Shuo Bai,2 Ziyi Zhang,2 Weiwei Yang4 1The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225003, People’s Republic of China; 2School of Nursing and Public Health, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 3Yangzhou Commission of Health, Yangzhou, Jiangsu, 225009, People’s Republic of China; 4Community Health Service Center, Yangzhou, Jiangsu, 225003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinsong Wang, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225003, People’s Republic of China, Tel +86 15952771632, Email wangjs@yzu.edu.cnPurpose: To explore the mediating effect of self-efficacy in the relationship between glycated haemoglobin (HbA1c) levels and health beliefs in community elderly patients with type 2 diabetes.Patients and Methods: From January to March 2022, convenience sampling was adopted to investigate 200 elderly patients with type 2 diabetes in a community in Yangzhou, China. Data were collected using the Health Beliefs Questionnaire, Self-efficacy for Diabetes, and Medication Compliance Questionnaire. Laboratory parameters included HbA1c, fasting blood glucose, postprandial blood glucose, total cholesterol, triglyceride, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol levels. Correlation, linear regression, and mediation analyses were performed using SPSS 27.0.Results: HbA1c levels were higher in men (women vs men: 6.80% [6.08%, 7.73%] vs.7.30% [6.30%, 9.18%]) and employed (employed vs not employed vs retired: 7.60% [6.90%, 10.45%] vs 5.85% [5.40%, 6.95%] vs 7.10% [6.20%, 8.20%]) and low self-efficacy (low vs high: 13.1% [6.55%, 13.85%] vs 6.8% [6.10%, 7.70%]). HbA1c levels were negatively associated with health beliefs (r = − 0.246) and self-efficacy (r = − 0.240; p< 0.01). Linear regression showed that perceived susceptibility, severity, benefit, and barriers, cues to action, and self-efficacy explained 50% of the variance in HbA1c levels after adjusting for sex and current work status. The mediation effect of self-efficacy was partial between health beliefs and HbA1c levels and accounted for 24.65% of the total effect (p < 0.001).Conclusion: Health beliefs influenced the improvement of self-efficacy in older patients with type 2 diabetes mellitus, which in turn could improve HbA1c control. Self-efficacy plays a partial mediating role between health beliefs and Hba1c levels in elderly patients with type 2 diabetes.Keywords: health belief model, self-efficacy, glycated haemoglobin, mediation analysis, elderly, type 2 diabetes mellitus

Keke Zhang,1 Xinxing Wan,1 Md Asaduzzaman Khan,2 Xiaoying Sun,1 Xuan Yi,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng3 1Department of Endocrinology, the Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2The Research Centre for Preclinical Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Nephrology, the First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, the First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, the Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Type 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN.Patients and Methods: Twenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools.Results: There were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN.Conclusion: Our study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.Keywords: circRNAs microarray, diagnostic biomarkers, early type 2 diabetic nephropathy, inflammation

ObjectiveThe objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects.Data sourcesWe searched 6 online-databases (Jul-Dec 2022) using terms: “mental practice,” “motor imagery training,” “motor imagery practice,” “mental training,” “movement imagery,” “cognitive training,” “bilateral transfer,” “interlimb transfer,” “cross education,” “motor learning,” “strength,” “force” and “motor performance.”Study selection and data extractionWe selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis.Data synthesisThe meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT).ResultsMIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57–0.98). The effect of MIT on BT was similar to that of PT (ES = –0.02, 95% CI = –0.15–0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57–2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74–1.17), and mixed-task (ES = 1.68, 95% CI = 1.26–2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14–0.78) and normal-task (ES = 0.56, 95% CI = 0.23–0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37–0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59–1.15).ConclusionThis review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors.

Zhi Wen,1,&ast; Xin Wan,2,&ast; Chen-Xing Qi,1 Xin Huang1 1Department of Ophthalmology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen-Xing Qi; Xin Huang, Department of Ophthalmology, Jiangxi Provincial People’s Hospital, No. 152, Ai Guo Road, Dong Hu District, Nanchang, Jiangxi, People’s Republic of China, Email 2013302180181@whu.edu.cn; 334966891@qq.comPurpose: To explore the alterations in both local and remote brain connectivity in patients with thyroid-associated ophthalmopathy (TAO) and to investigate whether the alterations of local neural function could be used to distinguish patients with TAO from healthy controls (HCs) using support vector machine (SVM) classifier.Materials and Methods: In total, 21 patients with TAO and 21 well-matched HCs were enrolled in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We employed regional homogeneity (ReHo) algorithm to evaluate local neural function and selected significantly altered brain regions as seed areas for subsequent study of the remote functional connectivity (FC). Moreover, we chose the observed alterations in the ReHo analysis as classification features to differentiate patients with TAO from HCs through SVM classification method.Results: Compared with the HCs, TAO patients showed significantly lower ReHo values in the right middle occipital gyrus (MOG) and right angular (ANG). In contrast, TAO patients displayed higher ReHo values in the left hippocampus (Hipp). We further found TAO patients exhibited decreased FC between the left and right Hipp, right MOG and left cerebellum (CER), right ANG and left rectus, right superior temporal pole gyrus (PSTG) (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The alterations in local neural function exhibited an accuracy of 78.57% and area under curve of 0.81 for distinguishing the patients from HCs.Conclusion: We mainly found the results that patients with TAO showed significantly dysfunctional local and remote brain functional connectivity in several brain regions associated with visual and cognitive functions. The ReHo variability has potential value in differentiating patients with TAO from HCs. These findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.Keywords: thyroid-associated ophthalmopathy, functional magnetic resonance imaging, regional homogeneity, functional connectivity, machine learning

ObjectiveThe current review was aimed to determine the effectiveness of mental imagery training (MIT) on the enhancement of maximum voluntary muscle contraction (MVC) force for healthy young and old adults.Data sourcesSix electronic databases were searched from July 2021 to March 2022. Search terms included: “motor imagery training,” “motor imagery practice,” “mental practice,” “mental training,” “movement imagery,” “cognitive training,” “strength,” “force,” “muscle strength,” “performance,” “enhancement,” “improvement,” “development,” and “healthy adults.”Study selection and data extractionRandomized controlled trials of MIT in enhancing muscle strength with healthy adults were selected. The decision on whether a study met the inclusion criteria of the review was made by two reviewers independently. Any disagreements between the two reviewers were first resolved by discussion between the two reviewers. If consensus could not be reached, then it would be arbitrated by a third reviewer.Data synthesisTwenty-five studies including both internal MIT and external MIT were included in meta-analysis for determining the efficacy of MIT on enhancing muscle strength and 22 internal MIT were used for subgroup analysis for examining dose-response relationship of MIT on MVC.ResultsMIT demonstrated significant benefit on enhancing muscle strength when compared with no exercise, Effect Size (ES), 1.10, 95% confidence interval (CI), 0.89–1.30, favoring MIT, but was inferior to physical training (PT), ES, 0.38, 95% CI, 0.15–0.62, favoring PT. Subgroup analysis demonstrated that MIT was more effective for older adults (ES, 2.17, 95% CI, 1.57–2.76) than young adults (ES, 0.95, 95% CI, 0.74–1.17), p = 0.0002, and for small finger muscles (ES, 1.64, 95% CI, 1.06–2.22) than large upper extremity muscles (ES, 0.86, 95% CI, 0.56–1.16), p = 0.02. No significant difference was found in the comparison of small finger muscles and large lower extremity muscles, p = 0.19 although the ES of the former (ES, 1.64, 95% CI, 1.06–2.22) was greater than that of the later (ES, 1.20, 95%, 0.88–1.52).ConclusionThis review demonstrates that MIT has better estimated effects on enhancing MVC force compared to no exercise, but is inferior to PT. The combination of MIT and PT is equivalent to PT alone in enhancing muscle strength. The subgroup group analysis further suggests that older adults and small finger muscles may benefit more from MIT than young adults and larger muscles.

Hong Lang,1 Xin Wan,2 Mengqing Ma,1 Hui Peng,1 Hao Zhang,2 Qing Sun,1 Li Zhu,1 Changchun Cao1 1Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Changchun CaoDepartment of Nephrology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211166, Jiangsu, People’s Republic of China, Email caochangchun@njmu.edu.cnBackground: Acute kidney injury (AKI) is a severe complication of cardiac surgery. This study was designed to explore the association between the preoperative low T3 syndrome and cardiac surgery-associated acute kidney injury (CSA-AKI).Methods: This was a retrospective single-center study. Data on 784 patients undergoing elective coronary artery bypass grafting (CABG) or valve surgery were collected from January 2016 to July 2019. AKI was defined according to Kidney Disease: Improving Global Outcomes guidelines. The effect of preoperative low T3 syndrome (fT3 < 3.5pmol/L) on the risk of the postoperative AKI was analyzed in a logistic regression model.Results: There were 171 (21.8%) patients developing AKI. Preoperative T3 and FT3 levels were lower in patients with AKI than in those without AKI (P < 0.001). The incidence of postoperative AKI was higher in patients with low T3 syndrome than in those without (31.0% vs 19.8%; P = 0.003). Multivariate logistic regression analysis showed that low T3 syndrome was an independent risk factor for CSA-AKI patients (OR = 1.609, 95% CI: 1.033– 2.504; P = 0.035), after adjusting for confounding factors, such as age, albumin, and uric acid. Subgroup analyses showed that preoperative low T3 syndrome also increased incidence of CSA-AKI in those with high risk factors, such as age ≧60 yrs (OR: 1.891, 95% CI: 1.183– 3.022, P = 0.008), hypertension (OR: 2.104, 95% CI: 1.218– 3.3.635, P = 0.008), and hyperuricemia (OR: 2.052, 95% CI: 1.037– 4.06, P = 0.039).Conclusion: Low T3 syndrome independently increases the risk of CSA-AKI. Patients with low T3 syndrome should be considered at higher risk and be evaluated before cardiac surgery.Keywords: acute kidney injury, cardiac surgery, low triiodothyronine syndrome, risk factor

Dawei Chen,1 Linglin Jiang,1 Jing Li,2 Yan Tan,3 Mengqing Ma,4 Changchun Cao,4 Jing Zhao,1 Xin Wan1 1Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Nephrology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Xin WanDepartment of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaEmail wanxin@njmu.edu.cnPurpose: Both acute respiratory failure (ARF) and acute kidney injury (AKI) are two common complications in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Moreover, both ARF and AKI are reported as increasing the risk of mortality of patients with AECOPD. However, the interaction of ARF and AKI on the mortality of patients with AECOPD remains unknown. Therefore, the aim of this study is to investigate the joint effect of ARF and AKI on in-hospital mortality in AECOPD patients.Patients and Methods: We performed a retrospective, observational cohort study of data from Nanjing First Hospital. The effect of AKI and ARF on in-hospital mortality was assessed using a multivariate logistic regression model. Additive interaction was assessed with the relative excess risk due to interaction.Results: A total of 1647 participants were enrolled. ARF and AKI occurred in 515 (31.3%) and 357 (21.7%) patients, respectively. Overall, in-hospital mortality was 5.7%. The in-hospital mortality of the neither ARF nor AKI group, the ARF only group, the AKI only group, and both the ARF and AKI group were 0.8%, 7.0%, 7.5%, and 29.9%, respectively. After multivariate logistic regression analysis, the independent factors for in-hospital death included: albumin (OR 0.88, 95% CI 0.83– 0.93, P < 0.001), ARF only (OR 8.53, 95% CI 3.64– 19.99, P < 0.001), AKI only (OR 8.99, 95% CI 3.58– 22.55, P < 0.001), and both ARF and AKI (OR 39.13, 95% CI 17.02– 89.97, P < 0.001). The relative excess risk due to interaction was 22.62 (95% CI, 0.31 to 44.93), the attributable proportion due to interaction was 0.59 (95% CI, 0.36 to 0.79), and the synergy index was 2.46 (95% CI, 1.44 to 4.20), indicating ARF and AKI had a significant synergic effect on in-hospital mortality.Conclusion: ARF and AKI had a synergistic effect on in-hospital mortality in AECOPD patients.Keywords: acute respiratory failure, acute kidney injury, in-hospital mortality, acute exacerbation chronic obstructive pulmonary disease

Ting Ye,1,&ast; Jia Feng,1,&ast; Meng Cui,2 Jia Yang,2 Xue Wan,1 Dan Xie,1 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Laboratory Medicine, The Leshan People’s Hospital, Luzhou, Sichuan, 614000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Ye; Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of ChinaTel +86-830-3165730Email yeting1103@163.com; liulab2019@163.comBackground: Myocardial infarction associated transcript (MIAT) is identified as a long chain non-coding RNA (lncRNA), which was associated with myocardial infarction susceptibility. While intense efforts have been made to elucidate the relationship between MIAT and carcinogenesis, the tumor immunoreaction of MIAT remains elusive. Thus, this study aimed to investigate the role of MIAT in the immunoregulation of breast cancer (BC) and further explore the better clinical significance.Methods: The differential expression of MIAT between BC and normal/adjacent tissues was compared using Wilcoxon rank sum test. The diagnostic and prognostic values of elevated MIAT expression in BC tissues were unveiled via receiver operating characteristic (ROC) analysis and KM-plotter analysis. Limma and edgeR package were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) from TCGA database respectively. A co-expression dataset was constructed to comprehensively understand the relationship between MIAT and DEGs based on the Pearson correlation coefficient. Furthermore, GO and KEGG analyses were conducted to predict the potential functions of MIAT. We next intersected immune-related genes (IRGs) from ImmPort database with MIAT-co-expressed genes to obtain MIAT-co-expressed IRGs, in order to construct MIAT-microRNA (miRNA)-mRNA network. And the correlation between MIAT and tumor-infiltrating immune cells (TICs) and immunophenoscore (IPS) analysis was analyzed by TIMER and CIBERSORT. Finally, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression profiles of MIAT in serum samples.Results: The expression levels of MIAT were notably higher in BC than in normal or adjacent tissues. And MIAT expression could be used as a prognostic indicator of mortality risk in patients with BC in different aspects. Moreover, the enrichment analyses suggested that MIAT was strongly involved in BC immune response. In addition, TIMER database and CIBERSORT analyses indicated that MIAT was significantly correlated with 13 types of TICs (B cells, dendritic cells, neutrophils, CD8 T cells, CD4 memory resting T cells, CD4 memory activated T cells, gamma delta T cells, M1 macrophages, plasma cells, activated NK cells, monocytes, M2 macrophages, activated mast cells). Simultaneously, the IPS analysis implied that the higher the MIAT expression, the better the immunotherapy effect. The ROC curve analysis showed that the area under the curve (AUC) value of MIAT was 0.86 (sensitivity = 87.80%, specificity = 75.61%). And the high MIAT expression in serum was positive related to TNM stage (P = 0.032) and lymph node metastasis (P = 0.028).Conclusion: MIAT may be a valuable noninvasive diagnostic biomarker for BC and is associated with tumor-infiltrating immune cells in tumor microenvironment, suggesting MIAT as a potential target for future treatment of BC.Keywords: lncRNA MIAT, BC, biomarker, immune regulation, tumor-infiltrating, immune cells

Huogen Liu, Xin Wan, Yundi Shi, Fengming Huang, Hailin Shu, Rijin Huang, Ling Gu Department of Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fu’an City, Fujian Province, 355000, People’s Republic of ChinaCorrespondence: Ling GuDepartment of Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, No. 89 Heshan Road, Fu’an City, Fujian Province, 355000, People’s Republic of ChinaEmail green660405@163.comBackground: Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to reflect early renal dysfunction. We investigated the predictive significance of serum NGAL in predicting cardiovascular (CV) death in an old-age population with coronary heart disease (CHD).Methods: In total, 633 CHD patients with a stable clinical condition were enrolled. The measurements of serum NGAL and other laboratory indices were performed within 24 hours after admission. Adjusted analysis was used to assess relationships between serum NGAL and CV death during the 10-year follow-up period.Results: Multivariate logistic regression analysis demonstrated that elevated NGAL levels were related to a higher prevalence of CV disease history [quartile 4, 2.41 (1.60– 4.59), P-trend < 0.001]. The Kaplan–Meier curve indicated that patients with high NGAL levels tended to have a higher rate of CV death than patients with low NGAL levels. A multivariate Cox model suggested that increased levels of NGAL were independently linked with elevated risk of CV death (HR=2.62, 95% CI 1.51– 4.96, P< 0.001) during the 10-year follow-up period, after adjusting for related confounding factors using sensitivity analysis. Furthermore, the receiver operating characteristics (ROC) curve demonstrated that serum NGAL (AUC=0.917, 95% CI 0.895– 0.940, P< 0.001) had an ideal predictive value in predicting CV death.Conclusion: Serum levels of NGAL were elevated in patients with CHD and may be a new parameter that could independently predict CV death in these patients, which may strengthen its potential application in clinical practice.Keywords: neutrophil gelatinase-associated lipocalin, cardiovascular death, ischemic heart disease

Yongfei You,1 Panpan Wang,1 Xi Wan,2 Liping Xu,3 Yi Gong,4 Weihua Zhang1 1Department of Oncology, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Operating Room, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 3Department of Pathology, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of China; 4Department of Imaging, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People’s Republic of ChinaCorrespondence: Yongfei YouDepartment of Oncology, The First Hospital of Nanchang, Xiangshan North Road, Donghu District, Nanchang, Jiangxi, 330008, People’s Republic of ChinaTel +86 15070836919Email 59185325@qq.comAbstract: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high rates of recurrence and metastasis. There are no standard treatment options available for patients with recurrence and metastases. The case of a 61-year-old male with SDC of the left parotid gland is presented in this study. The results revealed that the patient’s tumour had strong positive staining for androgen receptor (AR) expression, mutations in HRAS and PIK3CA but not in other related genes, and no gene amplification of HER-2. After the primary therapy of parotidectomy with neck dissection and postoperative radiation, bone metastases were found in the ribs, pelvis and spine. Androgen deprivation therapy (ADT) involving combined androgen blockade (CAB) was effective as the first-line therapy for the patient’s metastases and resulted in a progression-free survival (PFS) of over 7 months to date. In conclusion, androgen deprivation therapy is recommended for patients with recurrent or metastatic SDC positive for androgen receptor expression.Keywords: salivary duct carcinoma, androgen receptor, androgen deprivation therapy, case report

Yijia Wang,1,* Chunze Zhang,2,* Shaobin Hou,3 Xiaojing Wu,1 Jun Liu,4 Xuehua Wan5 1Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 2Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 3Advanced Studies in Genomics, Proteomics, and Bioinformatics, University of Hawaii at Manoa, Honolulu, HI, USA; 4Department of Radiology, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 5TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun LiuTianjin Union Medical Center, No. 190, Jieyuan Road, Hongqiao District, Tianjin City, People’s Republic of ChinaEmail junliu_sci@163.comXuehua WanNankai University, No. 94, Weijin Road, Nankai District, Tianjin City, People’s Republic of ChinaEmail xuehua.wan@hotmail.comIntroduction: Besides genetic and epigenetic alterations that lead to carcinogenesis and development of colorectal cancer (CRC), intestinal microbiomes are recently recognized to play a critical role in CRC progression. The abundant species associated with human CRC have been proposed for their roles in promoting tumorigenesis. However, a recent “driver-passenger” model suggests that these CRC-associated species with high relative abundances may be passenger bacteria that take advantage of the tumor environment instead of initiating CRC, whereas the driver species that initiate CRC have been replaced by passenger bacteria due to the alteration of the intestinal niche.Methods: Here, to reveal potential driver and passenger bacteria during CRC progression, we compare the gut mucosal microbiomes of 75 triplet-paired CRC samples collected from on-tumor site, adjacent-tumor site, and off-tumor site, and 26 healthy controls.Results: Our analyses revealed potential driver bacteria in four genera and two families, and potential passenger bacteria in 14 genera or families. Bacillus, Bradyrhizobium, Methylobacterium, Streptomyces, Intrasporangiaceae and Sinobacteraceae were predicted to be potential driver bacteria. Moreover, 14 potential passenger bacteria were identified and divided into five groups. Group I passenger bacteria contain Fusobacterium, Campylobacter, Streptococcus, Schwartzia, and Parvimonas. Group II passenger bacteria contain Dethiosulfatibacter, Selenomonas, Peptostreptococus, Leptotrichia. Group III passenger bacteria contain Granulicatella. Group IV passenger bacteria contain Shewanella, Mogibacterium, and Eikenella. Group V passenger bacteria contain Anaerococus. Co-occurrence network analysis reveals a low correlation relationship between driver and passenger bacteria in CRC patients compared with healthy controls.Discussion: These driver and passenger species may serve as bio-marker species for screening cohorts with high risk to initiate CRC or patients with CRC, respectively. Further functional studies will help understand the roles of driver and passenger bacteria in CRC initiation and development.Keywords: colorectal cancer, driver-passenger model, microbiota

Xue Wan,1 Heqing Zhang,1 Yahan Zhang,2 Yulan Peng1 1Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of ChinaCorrespondence: Yulan Peng Tel/Fax +86 18980601606Email yulanpeng@163.comObjective: This article aims to provide a better understanding of ultrasonography and immunohistochemistry of secondary nonhematological tumors of breast.Methods: The study reviewed the ultrasound findings and immunohistochemical features of nonhematological metastatic breast tumor cases found in patients of West China Hospital, Sichuan University from 2007 to 2019. Each case was categorized as secondary breast malignancy using histopathological results.Results: Fourteen cases were identified from West China Hospital database. Ten cases originated in the lung, 2 cases in the stomach, 1 case in the ovary and 1 case of neuroendocrine carcinomas. Fourteen masses were evaluated. Ultrasound findings showed that tumors were hypoechoic (14/14), irregular (13/14), indistinct margin (13/14), along a long axis parallel to the skin (11/14), lacked vascularity via color doppler flow imaging (9/14). Eight cases showed no posterior features. Calcification was found in 1 case of lung adenocarcinoma that had metastasized to the breast. Abnormal axillary lymph nodes were detected in 5 cases. Immunohistochemical analysis showed that estrogen receptor (ER) and progesterone receptor (PR) were both negative in 11 cases, including gastric and lung cancer metastasis. One case of ovarian metastasis was positive for ER and negative for PR. Six patients were positive for cytokeratin 7 (CK7) and negative for cytokeratin 20 (CK20), including lung and ovarian carcinoma metastasis. Thyroid transcription factor-1 (TTF-1) was positive in 9 of 10 pulmonary carcinoma metastases. The patient of ovarian metastasis was positive for Wilms’ tumour 1 (WT-1) and carbohydrate antigen 125 (CA125). Two cases from gastric metastasis were positive for caudal-type homeobox 2 (CDX2).Conclusion: Although breast ultrasound is not useful in distinguishing metastases from primary breast cancer, it is helpful in diagnosing breast lesions as oncological diseases and provide evidence for further examination of patients. Immunohistochemistry plays an important role in distinguishing secondary breast cancer from primary, especially in patients without tumor history.Keywords: breast secondary carcinomas, ultrasonography, immunohistochemistry, clinical history

Ling Gu,1 Huogen Liu,1 Xianhong Liu,2 Xi Zeng,3 Zuchen Lei,1 Xin Wan1 1Department of Critical Care Medicine, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of China; 2Department of Nephrology, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of China; 3Department of Geriatrics, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of ChinaCorrespondence: Xin WanDepartment of Critical Care Medicine, Mindong Hospital of Fujian Medical University, No. 89 Heshan Road, Fuan City 355000, Fujian Province, People’s Republic of ChinaTel +86 15259367910Email wancy505@163.comBackground: Cardiovascular diseases (CVDs) are the main cause of death in patients with chronic kidney disease (CKD). Interleukin-4 (IL-4) is considered an inflammatory cytokine. However, few studies have investigated the association between serum IL-4 and cardiovascular events in CKD. This study investigated whether serum IL-4 levels were associated with an increased risk of cardiovascular (CV) events in patients with CKD.Patients and Methods: A total of 302 patients with stage 1– 5 CKD were followed up for a mean of 32 (range=4– 36) months for end points (CV events). Serum IL-4 levels were measured at baseline. The independent relationship between serum IL-4 and the risk of CV events was assessed with multivariate Cox regression analysis.Results: The average age of this cohort (N=302) was 65.4 years. A total of 69.9% of them were male. CV events numbered 41 (13.6%) during the follow-up period. The Kaplan–Meier analysis showed that the rate of CV events was higher in patients with CKD with IL-4 levels above the mean (126.2 pg/mL) than in those with IL-4 levels below the mean. The multivariate Cox proportional hazard analysis revealed that serum IL-4 (HR=1.650, 95% CI 1.266– 2.210, P< 0.001) was associated with CV events in these patients with CKD. Sensitivity analysis showed that the association between serum IL-4 and CV events was not affected by the use of anti-inflammatory medication. The significant association between higher IL-4 levels and increased risk of CV events existed in patients with CKD3-5 but not in patients with CKD1-2 by using the stratified analysis.Conclusion: Higher serum IL-4 levels were associated with an increased risk of CV events during follow-up. Elevated serum IL-4 levels may help clinicians predict early CV events in patients with CKD.Keywords: interleukin-4, chronic kidney disease, cardiovascular event, Cox regression, prognosis

Ke Chen,1 Xinxing Wan,1 Liling Zhao,1 Shaoli Zhao,1 Lin Peng,2 Wenjun Yang,1 Jingjing Yuan,1 Liyong Zhu,3 Zhaohui Mo1 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Nephrology, The First Hospital of Changsha, Changsha, Hunan 410005, People’s Republic of China; 3Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Zhaohui Mo Tel/Fax +86 731 88618006Email easd04mzh@126.comBackground: Multiple symmetric lipomatosis (MSL) is a rare disease showing chronic progression of multiple, symmetrical, and non-encapsulated subcutaneous lipoma. The cause of the disease remains unknown.Patients and Methods: This study reported and summarized 13 sporadic cases of Type I MSL patients in terms of histopathology and cellular and molecular biology and assessed the CBLB c.197A>T mutation in the IRS1-PI3K-Akt pathway.Results: The clinical data showed that these 13 Type I patients were all male with a mean age of 57.0 ± 6.6 years old and consumed alcohol heavily. The laboratory tests revealed that most of the patients had hyperuricemia, diabetes, hyperinsulinemia, or insulin resistance; however, their blood lipid levels were close to a normal range. The imaging data exhibited lipomas that only occurred subcutaneously but not viscerally, ie, Types Ia (15.4%), Ib (30.8%), and Ic (53.8%). The molecular analyses of adipocytes of isoprenaline stimulated human adipose tissue-derived mesenchymal stromal cells (hADSCs) isolated from the adipose tissue lipoma-like masses (ATLLM) demonstrated that these adipocytes did not express UCP-1. The Cbl proto-oncogene B (CBLB), an E3 ubiquitin-protein ligase, was associated with insulin resistance and obesity and was mutated (ie, CBLB c.197A>T) in four MSL patients after the whole genome and Sanger sequencing of the blood samples. Furthermore, the CBLB c.197A>T mutation induced hADSC resistance to insulin by inactivation of the IRS-1-PI3K-AKT pathway.Conclusion: This study analyzed clinical, histopathological, and cellular and molecular biological characterizations of 13 Type I MSL patients and identified the CBLB c.197A>T heterozygous mutation that could be responsible for MSL metabolic dysfunction or even MSL development.Keywords: multiple symmetric lipomatosis, MSL, manifestation, characterization, CBLB

Jun Luo1 ,* Dan Wang2 ,* Xuechao Wan,2 Yangguang Xu,2 Yali Lu,2 Zhe Kong,2 Dujian Li,1 Wei Gu,1 Chenji Wang,2 Yao Li,2 Chaoneng Ji,2 Shaohua Gu,2 Yaoting Xu1 1Department of Urology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaohua Gu; Yaoting Xu Email shaohuagu@fudan.edu.cn; ytxu64@vip.163.comIntroduction: Prostate cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of cancer-related death in males in the United States. Despite the initial efficacy of androgen deprivation therapy in prostate cancer (PCa) patients, most patients progress to castration-resistant prostate cancer. However, the mechanisms underlying the androgen-independent progression of PCa remain largely unknown.Methods: In this study, we established a PCa cell line (LNCaP-AI) by maintaining LNCaP cells under androgen-depleted conditions. To explore the cellular and molecular mechanisms of androgen-independent growth of PCa, we analyzed the gene expression patterns in androgen-independent prostate cancer (AIPC) compared with that in androgen-dependent prostate cancer (ADPC). KEGG pathway analysis revealed that Wnt signaling pathways were activated after androgen deprivation therapy (ADT). In vitro experiments showed that the inhibition of Wnt pathway reduced AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. Furthermore, WNT5A, LEF1 were identified as direct targets of AR by chromatin immunoprecipitation (ChIP) assay and public ChIP-seq datasets analysis.Results: In the present study, we found a regulatory mechanism through which crosstalk between androgen receptor (AR) and Wnt signals promoted androgen-independent conversion of PCa. The Wnt pathway was inhibited by androgen in androgen-dependent prostate cancer cells, but this blocking effect was not elicited in androgen-independent prostate cancer (AIPC) cells. Moreover, Wnt pathway genes WNT5A and LEF1 were directly downregulated by AR. In vitro experiments showed that inhibition of the Wnt pathways repressed AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. We found that WNT5A and LEF1 were downregulated in low-grade PCa but upregulated in metastatic PCa.Conclusion: In summary, we revealed that crosstalk between AR and Wnt signaling pathways promotes androgen-independent growth of PCa, which may provide novel therapeutic opportunities for castration-resistant prostate cancer.Keywords: Wnt pathway, prostate cancer, androgen receptor, androgen deprivation therapy

Jinlin Li,1 Qi Wang,1 Qingping Zhang,2 Zhengyan Wang,1 Xin Wan,3 Chenfang Miao,4 Xi Zeng5 1Department of Respiratory Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei 441300, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei 441300, People’s Republic of China; 3Department of Critical Care Medicine, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of China; 4Department of Anesthesiology, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of China; 5Department of Geriatrics, Mindong Hospital of Fujian Medical University, Fuan, Fujian 355000, People’s Republic of ChinaCorrespondence: Xi ZengDepartment of Geriatrics, Mindong Hospital of Fujian Medical University, No. 89 Heshan Road, Fuan City 355000, Fujian Province, People’s Republic of ChinaTel +86 18596658975Email 987295461@qq.comBackground: Vascular cell adhesion molecule-1 (VCAM-1) is associated with vascular-related inflammation and atherosclerosis. This study aimed to evaluate whether VCAM-1 can be used for an indication of increased risk of CV events in patients with COPD.Methods: Serum VCAM-1 levels were measured in 163 COPD patients. All COPD patients were prospectively followed up for a median period of 48 months (range=3– 54). Cox proportional hazard analysis was performed to evaluate the prognostic value of serum VCAM-1 for predicting CV events.Results: Serum VCAM-1 levels were higher in COPD patients with CV events than in those without CV events (1174.4± 365.3 ng/mL vs 947.8± 293.2 ng/mL; P< 0.001). The logistic regression analysis revealed that serum VCAM-1 (OR=1.750; 95% CI, 1.324– 2.428; Ptrend= 0.0012) was independently associated with CVD (cardiovascular disease) history after adjusting for age, sex, BMI, current smoker, current drinker, admission systolic and diastolic BP, LVEF and laboratory measurements in patients with COPD at baseline. The Kaplan–Meier analysis demonstrated that the rate of CV events was higher in COPD patients with serum VCAM-1 levels above the median (517.3 ng/mL) than in those with VCAM-1 levels below the median. The Cox proportional hazard analysis revealed that serum VCAM-1 (HR=2.617; 95% CI, 1.673– 5.328; Ptrend< 0.001) may be an independent prognostic factor for CV events in the COPD patients.Conclusion: Our results suggested that serum VCAM-1 was significantly and independently associated with CV events in COPD patients. The inflammatory marker may help clinicians predict CV complications early.Keywords: vascular cell adhesion molecule-1, chronic obstructive pulmonary disease, cardiovascular events, prognostic value

Yiran Li1 *, Qizhi He2 *, Shuangdi Li,1 Xiaoli Wen,3 Lei Ye,1 Kai Wang,3 Xiaoping Wan1 1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Wang Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Shanghai 200040, People’s Republic of ChinaTel +86 (021)-5403-7438Email kaiwangcn@yahoo.comXiaoping Wan Department of Gynecology, Shanghai First Maternity and Infant Hospital, Shanghai 200040, People’s Republic of ChinaTel +86 136-5191-7177Email wanxiaoping62@126.comObjective: To study the characteristics of polymerase epsilon (POLE) exonuclease domain mutations in Chinese patients with endometrial carcinoma (EC).Methods: This study analyzed data from 529 patients with EC in The Cancer Genome Atlas (TCGA) and 467 EC patients evaluated at the Shanghai First Maternity and Infant Hospital (SFMIH). POLE mutation heterogeneity was analyzed in paired curettage and hysterectomy samples from 120 SFMIH patients. Sanger sequencing identified mutations in the POLE exonuclease domain, and correlations between POLE mutation status and various clinicopathological features were determined by chi-squared testing and Cohen’s kappa analysis, with Kaplan–Meier survival curves generated to assess correlations between POLE mutation status and overall survival (OS).Results: Thirty-five mutations were identified in 467 samples (7.5%), and novel mutations were detected in the SFMIH cohort. Compared to the TCGA cohort, the SFMIH cohort had fewer POLE mutations when matched by age (< 60) and histology (endometrioid) (p < 0.001 and p = 0.010, respectively). In our study cohort, POLE mutations were significantly associated with adjuvant treatment (p = 0.029), and patients with POLE mutations who underwent chemoradiotherapy had a poor OS (p < 0.0001). Notably, shorter OS was significantly associated with POLE mutations in hysterectomy samples from patients aged > 60 years or with stage I disease in the paired curettage-hysterectomy group.Conclusion: The significant difference in POLE mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.Keywords: endometrial carcinoma, polymerase epsilon mutation, POLE mutation, Chinese cohort, hysterectomy, curettage specimens

Tonghua Du, Ying Shi, Shengnan Xu, Xiaoyu Wan, Haiyin Sun, Bin Liu Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Bin LiuDepartment of Breast Surgery, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun, Jilin 130041, People’s Republic of ChinaTel +86 13844823515Email liubin19810713@163.comAbstract: Breast cancer (BC) is the most common cancer and the leading cause of death in women. Advances in early diagnosis and therapeutic strategies have decreased the mortality of BC and improved the prognosis of patients to some extent. However, the development of drug resistance has limited the success rate of systemic therapies. Long non-coding RNAs (lncRNAs) are involved in drug resistance in BC via various mechanisms, which contribute to a complex regulatory network. In this review, we summarize the latest findings on the mechanisms underlying drug resistance modulated by lncRNAs in BC. In addition, we discuss the potential clinical applications of lncRNAs as targeted molecular therapy against drug resistance in BC.Keywords: long non-coding RNA, lncRNA, drug resistance, breast cancer, mechanism

Yujia Huang,1,2,* Qian Feng,3,* Huabo Jiang,1,* Wanding Zhou,1,2 Jinhong Chen,2 Jie Gao,4 Kai Wang,1 Xiaoping Wan,2 Yongsheng Yu1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, People’s Republic of China; 4Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Wan; Yongsheng Yu Email wanxiaoping61@126.com; yongshengyu@tongji.edu.cnPurpose: Besides the tumor cells themselves, solid tumors are comprised of numerous cell types including infiltrating immune cells such as tumor-associated macrophages (TAMs). TAMs are vital stromal components of host immune system and play a critical role in the development of cancer. TAMs can be divided into two subtypes: M1 tumor-suppressive macrophage and M2 tumor-supportive macrophage. To better address the observations of TAMs functional performance, we describe an in vitro system that mimics the populations of TAMs infiltrated into the tumor mass by using our disintegrable supramolecular gelatin (DSG) hydrogels, which are physically crosslinked by host-guest complexations.Materials and Methods: The host–guest interaction was adopted between the aromatic groups of gelatin and the photocrosslinkable acrylated β-cyclodextrins (Ac-β-CDs) to form the DSG hydrogels. The convenient macrophage/endometrial cancer cells heterospheroid 3D model was set up by DSG hydrogels. RT-PCR and Western blot assays were developed to evaluate the efficiencies of inducers on the macrophages. The ELISA and oxygen saturation assays were performed to measure the secretion of VEGF and consumption of oxygen of tumor and/or macrophages, respectively. To determine the antitumor effects of M2 reprogrammed macrophages in vitro and in vivo, migration assay and tumor xenograft model were used, respectively.Results: The host-guest complexations of DSG hydrogels were controllably broken efficiently by soaking into the solution of competitive guest monomers 1-adamantanamine hydrochloride. The DSG hydrogels help IFN-γ reprogram the M2 to M1 and then decrease the tumor/M2 reprogrammed macrophage cells heterospheroid secretion of VEGF and increase the relative oxygen saturation. Significantly, the co-cultural tumor/M2 reprogrammed group from the disintegrated DSG hydrogels reduced the migration of cancer cells in vitro and the tumor growth in vivo.Conclusion: We obtain a TAMs/tumor microenvironment-responsive 3D model based on the novel DSG hydrogels, and will be of utility in cancer therapy and drug discovery.Keywords: supramolecular hydrogel, disintegration, host-guest complexations, tumor mimic model, tumor-associated macrophages, TAMs

Xin Wan,1,2,* Dawei Chen,1,* Yan Tan,3 Mengqing Ma,2 Feng Zhang,1 Zhihe Liu,1 Yue Chen,1 Wei Shao,2 Changchun Cao2 1Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changchun CaoDepartment of Nephrology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Street, Nanjing, Jiangsu 211100, People’s Republic of ChinaEmail caochangchun@njmu.edu.cnPurpose: Little is known about the incidence, risk factors, and prognostic implications of acute kidney injury (AKI) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. In this study, we investigated the incidence, risk factors, and short-term outcomes of AKI in these patients.Patients and Methods: We analyzed the records of 1768 patients admitted to Nanjing First Hospital with a principal diagnosis of AECOPD. Of these, 377 patients had AKI.Results: AKI occurred in 377 patients (21%). Independent risk factors for AKI in patients with AECOPD were advanced age, coronary artery disease, anemia, cancer, chronic kidney disease, hypercapnic encephalopathy, acute respiratory failure, and mechanical ventilation. Patients with AKI had worse prognostic implications and were more likely to require mechanical ventilation (38.7% vs 19.1%, P< 0.001); non-invasive mechanical ventilation (38.2% vs 18.9%, P< 0.001); invasive mechanical ventilation (18.3% vs 3.1%, P< 0.001); intensive care unit (ICU) admission (33.7% vs 12.9%, P< 0.001); had a longer ICU stay (9 days vs 8 days, P=0.033) and longer hospitalization (13 days vs 10 days, P< 0.001); and higher in-hospital mortality (18.0% vs 2.7%, P< 0.001) than those without AKI. Multivariable analysis indicated that compared to patients without AKI, those with stage 1, 2, or 3 AKI had a 1.9-fold, 2.1-fold, or 6.0-fold increased risk of in-hospital death, respectively.Conclusion: AKI is common in patients with AECOPD requiring hospitalization. Patients with AKI have worse short-term outcomes. Thus, AKI may be a prognostic predictor of patient survival.Keywords: acute kidney injury, acute exacerbation of chronic obstructive pulmonary disease, incidence, risk factor, prognostic implication

Ting Ye,* Jia Feng,* Xue Wan, Dan Xie, Jinbo Liu Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medical, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou 646000, Sichuan, People’s Republic of ChinaTel +86830 3165730Email liulab2019@163.comAbstract: The dichotomy of cancer-regulatory genes into “oncogenes (OCGs)” and “tumor-suppressor genes (TSGs)” has greatly helped us in learning molecular details of tumor biology. SPDEF, known as the prostate-derived ETS factor, is reported to play a pivotal role in normal cell development and survival, which has also been endowed with dual characteristics in cancers. Breast cancer (BC) is a highly heterogeneous disease which becomes the leading reason for cancer-related fatality among women worldwide. The involvement of SPDEF in many aspects of BC has been postulated, whereas the mechanism governing the regulation of the pro- and anti-oncogenic activities of SPDEF in BC state remains poorly defined. In this review, we summarized SPDEF as the double agent involving in expression profiles, the regulatory mechanism in BC progression, as well as the role in diagnosis, treatment and prognosis of BC. The understanding of SPDEF duality has contributed to gain insight into the tumor biology and also add a new dimension to the new therapy targets for BC.Keywords: SPDEF, double agent, oncogenes, tumor-suppressor genes, transcription factor, breast cancer

Yang Yang,1,2,* Xinyu Liu,3,* Lulu Cheng,2 Li Li,2 Zhenyu Wei,4 Zong Wang,2 Gang Han,2 Xuefeng Wan,2 Zaizhong Wang,2 Jianhua Zhang,5 Chuanliang Chen1 1Henan Key Laboratory for Medical Imaging of Neurological Diseases, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 2Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian 463000, People’s Republic of China; 3School of Intelligent Manufacturing, The Huanghuai University, Zhumadian 463000, People’s Republic of China; 4Department of Neurosurgery, Second Affiliated Hospital of Xinxiang Medical College, Xinxiang 453000, People’s Republic of China; 5Medical Engineering Technology and Data Mining Institute of Zhengzhou University, Zhengzhou 450000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanliang ChenHenan Key Laboratory for Medical Imaging of Neurological Diseases, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of ChinaEmail chenchuanliangsy@126.comBackground: Low-grade gliomas (LGG), approximately constitute one-third of all types of gliomas, are prone to relapse and metastasis. MicroRNA-138 (miR-138) is reported to be dysregulated in diverse human tumors and mainly function as a tumor suppressor. In this study, we analyzed the expression profile and function of miR-138 in LGG.Methods: Quantitative PCR (qPCR) and public database bioinformatics analysis were performed to determine the miR-138 levels in LGG. MiR-138 overexpression in LGG cells was achieved by miR-138 mimics transfection. Cell proliferation was assessed by CCK8, EdU and colony formation assays. Cell invasion and migration were analyzed by transwell and wound-healing assays. Xenograft model was employed to study the role of miR-138 in LGG growth in vivo. The target of miR-138 was validated by multiple methods, such as luciferase reporter assay, RT-qPCR and Western blot. Bioinformatics analysis was conducted to explore the molecular mechanisms by which miR-138 contributed to LGG progression.Results: miR-138 was significantly downregulated in LGG tumor tissues and low expression of miR-138 was significantly associated with poor prognosis as well as relapse and metastasis in LGG patients. Functional analysis indicated that ectopic miR-138 expression suppressed LGG cell growth and invasive phenotype in vitro, and inhibited tumor development in vivo. Moreover, miR-138 directly targeted and repressed insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) by targeting the 3ʹ-UTR of IGF2BP2, inhibiting epithelial to mesenchymal transition (EMT) to attenuate LGG aggressiveness. In addition, we found that elevated IGF2BP2 expression correlates with poor survival of LGG patients.Conclusion: miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT in the progression of LGG.Keywords: miR-138, tumor prognosis, LGG, IGF2BP2, EMT

Man-Yu Dong, Bao-Lin Tang, Xiao-Yu Zhu, Si-Qi Cheng, Xin-Chen Fang, Juan Tong, Xiang Wan, Chang-Cheng Zheng, Hui-Lan Liu, Zi-Min Sun Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Zi-Min SunDepartment of Hematology, The First Affiliated Hospital of University of Science and Technology of China, No. 17, Lujiang Road, Hefei, Anhui 230001, People’s Republic of ChinaTel +86 551 6228 2992Fax +86 551 6228 2121Email zmsun_vip@163.comIntroduction: Current consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited.Patients and Methods: Wct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies < 1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls.Results: The results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07– 0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8+ T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20× 10 9/L vs 0.10× 10 9/L, p=0.021, respectively).Conclusion: DNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8+ T cells.Keywords: cord blood transplantation, cytomegalovirus, DNA load, relapse, acute myeloid leukemia, complete remission

Wenjun Lu,1 Xiaobin Wan,2 Limin Tao,1 Junhui Wan1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of General Surgery, The Third Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of ChinaCorrespondence: Limin Tao; Junhui WanDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zhengjie, Donghu District, Nanchang 330006, Jiangxi, People’s Republic of ChinaTel +86-13879136013; +86-13970974546Email taolmin07@163.com; wjunhui@hotmail.comObjective: Long non-coding RNAs (lncRNAs) have been identified as important players in tumorigenesis. LncRNA highly upregulated in liver cancer (HULC) has been identified as a key regulator in the progression of various cancers. However, the functional role and the mechanisms of HULC in regulating cervical cancer cell behavior remain unclear.Methods: HULC expression, miR-218 expression and TPD52 mRNA level in cervical cancer cells were examined by qRT-PCR. Cell proliferation was evaluated by MTT assay. Cell migration and invasion were examined by Transwell assay. TPD52 protein level was measured by Western blot. Dual-luciferase reporter assay was measured to verify the combination of HULC and miR-218 as well as miR-218 and TPD52.Results: HULC expression was upregulated in cervical cancer cell lines, and HULC promoted cervical cancer cell proliferation, migration and invasion. Mechanistically, HULC acted as a sponge of miR-218 to elevate expression of TPD52, a target of miR-218, and thereby promoted cervical cancer cell proliferation, migration, and invasion.Conclusion: HULC promotes cervical cancer cell proliferation, migration and invasion via miR-218/TPD52 axis.Keywords: HULC, miR-218, TPD52, cervical cancer cell proliferation

Ting Ye,* Xue Wan,* Jingyuan Li, Jia Feng, Jinglan Guo, Guangrong Li, Jinbo Liu Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86-0830-3165730Email liulab2019@163.comBackground: Breast cancer (BC) is the leading cause of malignancy death in females worldwide. While intense efforts have been made to elucidate the pathogeny, the molecular mechanism of BC remains elusive. Thus, this study aimed to investigate the role of PPEF1 in the progression of BC and further explore the better clinical significance.Methods: The diagnostic and prognostic values of elevated PPEF1 expression in BC were unveiled via public databases analysis. In addition, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and Protein–protein interaction (PPI) analysis were performed to explore the potential functions and molecular mechanisms of PPEF1 in BC progression. Experimentally, transwell and CCK-8 assays were carried out to estimate the effects of PPEF1 on the BC metastasis. Meanwhile, the differential expressions of PPEF1 in paraffin-embedded tissues and serum samples were, respectively, analyzed by Immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) kit.Results: The transcriptional levels of PPEF1 were higher in BC than in normal breast tissues or adjacent normal tissues. Moreover, survival analysis revealed that higher PPEF1 expression was negatively associated with overall survival (OS), all events-free (AE-free) and metastatic recurrence-free (MR-free) survival, and further was an independent risk factor of unfavorable prognosis in BC patients. Additionally, the present study provided the first evidence that PPEF1 participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Furthermore, PPEF1 promotes the BC progression and can be used as a noninvasive diagnostic marker. Noteworthy, the combined determination of serum PPEF1 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of BC.Conclusion: PPEF1 exerted a tumorigenic role and involved in molecular mechanism of tumorigenesis in BC which served as a promising biomarker for prognosis and diagnosis.Keywords: PPEF1, breast cancer, biomarker, molecular function, signaling pathway

Lu Zhou,1 Huiping Shi,2 Wenyu Shi,1 Li Yang,1 Yaping Zhang,1 Mengqi Xu,1 Xiufang Chen,1 Yanv Zhu,1 Hui Mu,1 Xiaochun Wan,3 Zhonghua Yang,3 Ying Zeng,3,* Hong Liu1,* 1Hematology Department, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; 3Shenzhen Bin De Bio Tech Co. Lid, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong LiuHematology Department, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu 226001, People’s Republic of ChinaEmail Hongliu63@126.comYing ZengShenzhen Bin De Bio Tech Co. Lid, Rich Industrial Park, Shenzhen 518055, People’s Republic of ChinaEmail ying.zeng@bindebio.comAbstract: Despite the prominent effects of BCR-ABL tyrosine kinase inhibitors (TKI) therapy in patients with chronic phase-chronic myeloid leukemia (CP-CML) and thus low incidence of blastic transformation, blast phase (BP)-CML remains a major therapeutic challenge in the TKI era. The “gatekeeper” mutation T315I in BCR-ABL1 kinase, which often coupled with a poor prognosis, is quite common and resistant to all TKIs except for ponatinib. The occurrence of T315I mutation in BP-CML makes the situation more complex. Anti-CD19 chimeric antigen receptor T cell (CAR-T) technology is a new immunotherapy which has significantly improved the efficacy of B cell hematologic malignances. Here we report a lymphoid BP-CML patient harboring T315I mutation who achieved complete molecular remission and returned to chronic phase by anti-CD19 CAR-T therapy. Our study provides a new therapeutic strategy for patients in BP-CML.Keywords: anti-CD19 CAR-T, BP-CML, BCR-ABL1, T315I

Hanchun Huang, Xueshuai Wan, Yi Bai, Jin Bian, Jianping Xiong, Yiyao Xu, Xinting Sang, Haitao ZhaoDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaBackground: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR)) and different American Joint Committee on Cancer (AJCC) T stages in patients with hilar cholangiocarcinoma.Methods: A total of 101 patients who underwent surgical treatment for hilar cholangiocarcinoma between 2003 and 2014 in Peking Union Medical College Hospital were retrospectively analyzed. Receiver-operating curves were used to calculate optimal cutoff values for the NLR and the PLR. Univariate and multivariate analyses were used to identify whether the NLR and PLR can independently predict different AJCC T stages.Results: Multivariate analysis showed that higher NLR and PLR independently predicted advanced AJCC T stages (OR 3.74, 95% CI 1.09–12.83, P=0.036; and OR 7.86, 95% CI 2.25–27.43, P=0.001, respectively). At a threshold of 2.75, the NLR was 75.9% sensitive and 66.7% specific for different AJCC T stages; at a threshold of 172.25, the PLR was 65.5% sensitive and 80.6% specific.Conclusion: Preoperative NLR and PLR can be used as independent predictors of different AJCC T stages in patients with hilar cholangiocarcinoma.Keywords: neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, hilar cholangiocarcinoma

Junjie Qu,* Binya Liu,* Bilan Li, Guiqiang Du, Yiran Li, Jingyun Wang, Laman He, Xiaoping Wan Department of Gynaecology, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai 201204, China *These authors contributed equally to this work Objective: The aim of this study was to examine the effect of TRIB3 on proliferation, apoptosis, and migration of endometrial cancer (EC) cells and explore the relationship between TRIB3 and AKT signaling pathway in EC progression. Methods: Immunohistochemical analysis was performed to measure the expression level of TRIB3 in normal endometrium tissues and EC tissues. Overexpression and shRNA knockdown techniques were applied by transfecting EC cells (ISK and AN3CA), and the effect of TRIB3 on EC cell biological behaviors was evaluated. Cell Counting Kit-8 and colony formation assays were utilized to investigate EC cell proliferation ability, and flow cytometry was performed to assess the apoptosis of EC cells. Moreover, the migration and invasion of EC cells were detected by transwell assay, and the levels of MMP-2 and MMP-9 were measured by ELISA. Additionally, Western blot analysis was carried out to determine the levels of AKT and p-AKT. Results: The expression level of TRIB3 was higher in EC than normal endometrium tissues, and its overexpression promoted apoptosis and suppressed proliferation of EC cells. Furthermore, TRIB3 retarded the migration and invasion of EC cells and decreased the levels of MMP-2 and MMP-9. Conversely, TRIB3 inhibition enhanced the expression levels of MMP-2 and MMP-9, and proliferation and migration of EC cells but suppressed their apoptosis. Similarly, TRIB3 overexpression reduced while its knockdown increased the level of p-AKT. Conclusion: TRIB3 inhibited proliferation and migration and promoted apoptosis of EC cells probably through regulating AKT signaling pathway. Keywords: endometrial carcinomas, Drosophila tribbles homolog 3, endometrium, shRNA knockdown, overexpression

Chang-chun Cao,1,* Da-wei Chen,2,* Jing Li,2 Meng-qing Ma,2 Yu-bao Chen,3 Yi-zhi Cao,4 Xi Hua,2 Wei Shao,1 Xin Wan2 1Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 2Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 4The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03–2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes. Keywords: acute exacerbation of COPD, community-acquired acute kidney injury, hospital-acquired acute kidney injury, short-term outcomes

Weiya Pei, Xin Wan, Khawar Ali Shahzad, Lei Zhang, Shilong Song, Xiaoxiao Jin, Limin Wang, Chen Zhao, Chuanlai Shen Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu 210009, China Purpose: Numerous nanomaterials have been reported in the treatment of multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). But most of these nanoscale therapeutics deliver myelin antigens together with toxins or cytokines and underlay the cellular uptake and induction of tolerogenic antigen-presenting cells by which they indirectly induce T cell tolerance. This study focuses on the on-target and direct modulation of myelin-autoreactive T cells and combined use of multiple regulatory molecules by generating a tolerogenic nanoparticle.Materials and methods: Poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) were fabricated by co-coupling MOG40–54/H-2Db-Ig dimer, MOG35–55/I-Ab multimer, anti-Fas, PD-L1-Fc and CD47-Fc and encapsulating transforming growth factor-β1. The resulting 217 nm tolerogenic nanoparticles (tNPs) were administered intravenously into MOG35–55 peptide-induced EAE mice, which was followed by the investigation of therapeutic outcomes and the in vivo mechanism.Results: Four infusions of the tNPs durably ameliorated EAE with a marked reduction of clinical score, neuroinflammation and demyelination. They were distributed in secondary lymphoid tissues, various organs and brain after intravenous injection, with retention over 36 h, and made contacts with CD4+ and CD8+ T cells. Two injections of the tNPs markedly decreased the MOG35–55-reactive Th1 and Th17 cells and MOG40–55-reactive Tc1 and Tc17 cells, increased regulatory T cells, inhibited T cell proliferation and elevated T cell apoptosis in spleen. Transforming growth factor-β1 and interleukin-10 were upregulated in the homogenates of central nervous system and supernatant of spleen cells.Conclusion: Our data suggest a novel therapeutic nanoparticle to directly modulate autoreactive T cells by surface presentation of multiple ligands and paracrine release of cytokine in the antigen-specific combination immunotherapy for T cell-mediated autoimmune diseases. Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, autoreactive T cells, immunotherapy, myelin oligodendrocyte glycoprotein, biomimetic nanoparticle

Su Liu,1,2,* Jun-Li Yao,1,3,* Xin-Xin Wan,1,* Zhi-Jing Song,1 Shuai Miao,1,2 Ye Zhao,1,2 Xiu-Li Wang,1,2 Yue-Peng Liu4 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; 2Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; 3Department of Anesthesiology, Xuzhou Children’s Hospital, Xuzhou, Jiangsu, China; 4Center of Clinical Research and Translational Medicine, Lianyungang Oriental Hospital, Lianyungang, Jiangsu, China *These authors contributed equally to this work Purpose: Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance. Methods: Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine. To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH) and tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA (siRNA) were used. To explore the mechanisms of Shh signaling in MIH and tolerance, brain-derived neurotrophic factor (BDNF) inhibitor K252 and anti-BDNF antibody were used. Results: Repeated administration of morphine produced obvious hyperalgesia and tolerance. The behavioral changes were correlated with the upregulation and activation of morphine treatment-induced Shh signaling. Pharmacologic and genetic inhibition of Shh signaling significantly delayed the generation of MIH and tolerance and associated neurochemical changes. Chronic morphine administration also induced upregulation of BDNF. Inhibiting BDNF effectively delayed the generation of MIH and tolerance. The upregulation of BDNF induced by morphine was significantly suppressed by inhibiting Shh signaling. In naïve mice, exogenous activation of Shh signaling caused a rapid increase of BDNF expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly suppressed smoothened agonist-induced hyperalgesia. Conclusion: These findings suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating BDNF expression. Inhibiting Shh signaling, especially during the early phase, may effectively delay or suppress MIH and tolerance. Keywords: sonic hedgehog, tolerance, hyperalgesia, brain-derived neurotrophic factor, spinal cord

Shunan Wang,1 Wei Guo,1 Xin Wan,1 Yongliang Teng,2 Xiaoge Zhou,3 Ou Bai1 1Department of Hematology, 2Department of Pathology, The First Hospital of Jilin University, Changchun, 3Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. It is highly responsive to chemotherapy, but the median event-free survival is very short and has a high rate of relapse even after performing allogeneic stem cell transplantation; thus, the discovery of novel agents for the treatment of BPDCN is urgent. Chidamide is a new oral isotype-selective histone deacetylase inhibitor (HDACi). It is proved to exert a well-characterized anticancer property in a wide range of hematological malignancies, especially lymphoma. Here, we report a 41-year-old man who used oral chidamide 30 mg twice per week for maintenance therapy after receiving complete remission. For the first time in this field, we had explored the efficiency of chidamide in the treatment of BPDCN and tried to give more choices to the therapy of this disease. Keywords: hematopoietic malignancy, skin lesions, maintenance therapy, histone deacetylase inhibitor

Yong-Feng Yang,1 Xiao-Hui Cao,1 Chao-En Bao,1 Xin Wan2 1Department of Radiation Oncology, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China Background: Gemcitabine (GEM) is the most widely utilized systemic agent in combination with radiation therapy (RT) for treating locally advanced pancreatic cancer (LAPC) in the concurrent setting. Despite recent interest in using two novel oral fluoropyrimidines (FUs), capecitabine and S-1, in this setting, there is a lack of randomized controlled trials (RCTs) to support this approach.Methods: Trials published between 1994 and 2014 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by two authors for inclusion. Demographic data, treatment response, objective response rate (ORR), progression-free and overall survival (PFS and OS, respectively), and toxicities were extracted and analyzed using comprehensive meta-analysis software (version 2.0).Results: Twenty-three cohorts with 843 patients were included: 497 patients were treated with GEM and 346 patients were treated with oral FU. Pooled OS was significantly higher at 1 and 2 years for S-1 plus RT than for GEM plus RT (relative risk [RR] 1.27; 95% confidence interval [CI], 1.00–1.65; P=0.03; and RR 1.75; 95% CI, 1.18–2.60, P=0.002, respectively), while 1-year PFS and ORR were not significantly different between S-1 and GEM-based chemoradiotherapy (P=0.37 and P=0.06, respectively). Additionally, comparable efficacy was found between capecitabine and GEM-based chemoradiotherapy in terms of OS, PFS, and ORR. As for grade 3 and 4 acute toxicity, oral FU plus RT significantly reduced the risk of developing hematologic toxicities, nausea, and vomiting when compared to GEM plus RT (P

Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC) than concentric contraction (CC) of human skeletal muscles despite lower activation level of the muscle associated with EC. It is unknown, however, whether the strength of functional coupling between the primary motor cortex (M1) and other involved areas in the brain differs as voluntary movements are controlled by a network of regions in the primary, secondary and association cortices. Examining fMRI-based functional connectivity (FC) offers an opportunity to measure strength of such coupling. To address the question, we examined functional MRI (fMRI) data acquired during EC and CC (20 contractions each with similar movement distance and speed) of the right first dorsal interosseous (FDI) muscle in 11 young (20-32 years) and healthy individuals and estimated FC between the M1 and a number of cortical regions in the motor control network. The major findings from the behavioral and fMRI-based FC analysis were that (1) no significant differences were seen in movement distance, speed and stability between the EC and CC; (2) significantly stronger mean FC was found for CC than EC. Our finding provides novel insights for a better understanding of the control mechanisms underlying voluntary movements produced by EC and CC. The finding is potentially helpful for guiding the development of targeted sport training and/or therapeutic programs for performance enhancement and injury prevention.

Mingliang Ji,1 Yan Lu,1 Lina Guo,2 Fengzhi Feng,1 Xirun Wan,1 Yang Xiang1 1Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Beijing, People's Republic of China Abstract: Endometrial carcinoma with a germ cell tumor component is a rare event. Here we report a uterine neoplasm with a unique combination of endometrioid adenocarcinoma and mixed germ cell malignant elements. A 28-year-old woman with abnormal vaginal bleeding, an abdominal mass, and elevated alfa-fetoprotein and beta-human chorionic gonadotropin (ß-hCG) levels had a history of biopsy of an omental mass and chemotherapy in another hospital one month before her referral to our department. Histologic examination of the mass removed from the omentum revealed an endometrioid adenocarcinoma with yolk sac tumor-like differentiation. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and removal of metastatic disease were then undertaken at our hospital. Postoperative chemotherapy was given. Eight months postoperatively, serum alfa-fetoprotein and ß-hCG rose again. Cases with primary yolk sac tumors of the endometrium or endometrial carcinoma with trophoblastic differentiation in the literature were reviewed. Keywords: endometrial carcinoma, yolk sac tumor, trophoblastic differentiation

Jing Zhao,1 Yang Xiang,1 Dachun Zhao,2 Tong Ren,1 Fengzhi Feng,1 Xirun Wan1 1Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: An epithelioid trophoblastic tumor (ETT) is a rare trophoblastic tumor originating from chorionic-type intermediate trophoblasts. Vaginal involvement in ETT in the form of isolated lesions has not been previously reported. A 43-year-old woman presented with vaginal wall cysts and was diagnosed with ETT by pathological examination after cystectomy. No clinical evidence of uterine involvement was found at diagnosis or during follow-up. The patient was treated with chemotherapy and surgery after the first recurrence and underwent follow-up for 8 months. The serum human chorionic gonadotropin titer remained at undetectable levels. Keywords: ETT, isolated lesions, vaginal involvement

Recent research on bilateral transfer suggests that imagery training can facilitate the transfer of motor skill from a trained limb to that of an untrained limb above and beyond that of physical practice. To further explore this effect, the present study examined the influence of practice duration and task difficulty on the extent to which imagery training and physical training influences bilateral transfer of a sequential key pressing task. In experiment 1, participants trained on the key pressing task using their non-dominant arm under one of three conditions (physical practice, imagery practice, and no practice). In a subsequent bilateral transfer test, participants performed the sequential task using their untrained dominant arm in either an original order or mirror-ordered sequence. In experiment 2, the same procedures were followed as in experiment 1 except that participants trained with their dominant arm and performed the bilateral transfer task with their non-dominant arm. Results indicated that with extended practice beyond what has been employed in previous studies, physical practice is more effective at facilitating bilateral transfer compared to training with imagery. Interestingly, significant bilateral transfer was only observed for transfer from the non-dominant to the dominant arm with no differences observed between performing the task in an original or mirror ordered sequence. Overall, these findings suggest that imagery training may benefit bilateral transfer primarily at the initial stages of learning, but with extended training, physical practice leads to larger influences on transfer.

Dongxu Wang1, Ethan Will Taylor2, Yijun Wang1, Xiaochun Wan1, Jinsong Zhang11Key Laboratory of Tea Biochemistry and Biotechnology, School of Tea and Food Science, Anhui Agricultural University, Hefei, Anhui, People’s Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, USAAbstract: Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se) has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG) was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size (“Nano-Se”), compared with Se compounds commonly used in dietary supplements, has significantly lower toxicity, without compromising its ability to upregulate selenoenzymes at nutritional levels and induce phase II enzymes at supranutritional levels.Keywords: epigallocatechin-3-gallate, chemoprevention, nanoparticles, selenium

Jinsong Zhang1, Ethan W Taylor2, Xiaochun Wan1, Dungeng Peng31School of Tea and Food Science, Anhui Agricultural University, Anhui, People's Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, 3Department of Biochemistry, Vanderbilt University, Nashville, TN, USABackground: Elemental selenium nanoparticles have emerged as a novel selenium source with the advantage of reduced risk of selenium toxicity. The present work investigated whether heat treatment affects the size, structure, and bioactivity of selenium nanoparticles.Methods and results: After a one-hour incubation of solution containing 80 nm selenium particles in a 90°C water bath, the nanoparticles aggregated into larger 110 nm particles and nanorods (290 nm × 70 nm), leading to significantly reduced bioavailability and phase II enzyme induction in selenium-deficient mice. When a solution containing 40 nm selenium nanoparticles was treated under the same conditions, the nanoparticles aggregated into larger 72 nm particles but did not transform into nanorods, demonstrating that the thermostability of selenium nanoparticles is size-dependent, smaller selenium nanoparticles being more resistant than larger selenium nanoparticles to transformation into nanorods during heat treatment.Conclusion: The present results suggest that temperature and duration of the heat process, as well as the original nanoparticle size, should be carefully selected when a solution containing selenium nanoparticles is added to functional foods.Keywords: nanoparticle, selenium, bioactivity, heat treatment