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Xue Li,1,* Dianhui Peng,2,* Xinbo Wu,2 Xiaolin Li,2 Junwen Liang,2 Hongjun Yin,2 Le Liu,2 Qian Yang,2 Weixin Dong,2 Chunxia Lu2 1College of Sports and Art, Shandong Sport University, Jinan City, Shandong Province, People’s Republic of China; 2Department of Sport Education, Hunan Normal University, Changsha City, Hunan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weixin Dong; Chunxia Lu, Email dongweixin@hunnu.edu.cn; luchunxia@hunnu.edu.cnObjective: Loneliness is a prevalent issue among rural left-behind children in China, adversely affecting their physical and mental well-being, as well as social stability. However, the influencing factors and potential mechanisms of loneliness have not yet been fully clarified. This study aims to validate the mediating roles of social anxiety and psychological resilience by examining the association between affective/cognitive empathy and loneliness among Chinese rural left-behind children.Methods: This cross-sectional survey employed a convenience sampling approach among Chinese left-behind children. A total of 540 participants aged 6 to 11 years old (Average age = 8.54, SD = 1.682) from 3 primary schools in Hunan Province completed the Children’s Loneliness Scale, Social Anxiety Scale for Children, The Chinese version of Connor-Davidson Resilience Scale, and Basic Empathy Scale. Data analysis was conducted using SPSS 27.0, Origin 2020, and Mplus 8.3.Results: Pearson correlation analyses suggested strong significant correlations among affective/cognitive empathy, loneliness, social anxiety, and psychological resilience. Path analyses indicated that the chain mediation effect size of social anxiety and psychological resilience was 0.016 between affective empathy and loneliness, while the chain mediation effect size between cognitive empathy and loneliness was − 0.011.Conclusion: Affective empathy positively correlates with loneliness among Chinese left-behind children through social anxiety and resilience, while cognitive empathy negatively correlates with loneliness. These findings suggest that left-behind children should enhance their cognitive empathy and psychological resilience to reduce their social anxiety, thereby mitigating their loneliness.Keywords: left-behind children, empathy, loneliness, social anxiety, resilience

Beiying Deng,1,2,* Junhai Zhen,3,* Zixuan Xiang,1,2,* Xiangyun Li,1,2 Cheng Tan,1,2 Ying Chen,1 Pengzhan He,1 Jingjing Ma,4 Weiguo Dong1,* 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, People’s Republic of China; 3Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cnBackground: Ulcerative colitis (UC) is a debilitating intestinal disorder that imposes a significant burden on those affected. Fatty acid metabolism plays a pivotal role in regulating immune cell function and maintaining internal homeostasis. This study investigates the biological and clinical significance of fatty acid metabolism within the context of UC.Methods: Gene expression profiles from patients with UC and healthy controls were retrieved, enabling the identification of differentially expressed genes (DEGs) specific to UC. These DEGs were then intersected with genes related to fatty acid metabolism, resulting in the identification of differentially expressed fatty acid metabolism-related genes (FAM-DEGs). Machine learning was employed to pinpoint key feature genes from the FAM-DEGs, which were subsequently used to construct a predictive UC model and to uncover molecular subtypes associated with fatty acid metabolism in UC. An animal model of UC was established using 3% dextran sulfate sodium (DSS) administration. Western blot analysis confirmed the expression levels of genes in intestinal tissues.Results: The machine learning analysis identified three pivotal genes—ACAT1, ACOX2, and HADHB—culminating in a highly predictive nomogram. Consensus cluster analysis further categorized 637 UC samples into two distinct subgroups. The molecular subtypes related to fatty acid metabolism in UC exhibited significant differences in gene expression, biological activities, and enrichment pathways. Immune infiltration analysis highlighted elevated expression of two genes (excluding HADHB) in subtype 1, which corresponded with a marked increase in immune cell infiltration within this subtype. Western blot analysis demonstrated that ACAT1, ACOX2, and HADHB expression levels in the DSS group were significantly reduced, paralleling those observed in the normal group.Conclusion: This study highlights the critical role of specific fatty acid metabolism-related genes in UC, emphasizing their potential as targets for therapeutic intervention and shedding light on the underlying mechanisms of UC progression.Keywords: fatty acid metabolism, ulcerative colitis, machine learning, biomarkers, pharmacology, immune infiltrations

Junhai Zhen,1 Chuan Liu,2 Jixiang Zhang,2 Fei Liao,2 Huabing Xie,1 Cheng Tan,2 Ping An,2 Zhongchun Liu,3 Changqing Jiang,4 Jie Shi,5 Kaichun Wu,6 Weiguo Dong2 1Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 4Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 5Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100032, People’s Republic of China; 6Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China, Tel/Fax +8629-84771600, Email kaicwu@fmmu.edu.cn Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel/Fax +8627-88041911, Email dongweiguo@whu.edu.cnPurpose: Impaired quality of life (QOL) is common in patients with inflammatory bowel disease (IBD). A tool to more quickly identify IBD patients at high risk of impaired QOL improves opportunities for earlier intervention and improves long-term prognosis. The purpose of this study was to use a machine learning (ML) approach to develop risk stratification models for evaluating IBD-related QOL impairments.Patients and Methods: An online questionnaire was used to collect clinical data on 2478 IBD patients from 42 hospitals distributed across 22 provinces in China from September 2021 to May 2022. Eight ML models used to predict the risk of IBD-related QOL impairments were developed and validated. Model performance was evaluated using a set of indexes and the best ML model was explained using a Local Interpretable Model-Agnostic Explanations (LIME) algorithm.Results: The support vector machine (SVM) classifier algorithm-based model outperformed other ML models with an area under the receiver operating characteristic curve (AUC) and an accuracy of 0.80 and 0.71, respectively. The feature importance calculated by the SVM classifier algorithm revealed that glucocorticoid use, anxiety, abdominal pain, sleep disorders, and more severe disease contributed to a higher risk of impaired QOL, while longer disease course and the use of biological agents and immunosuppressants were associated with a lower risk.Conclusion: An ML approach for assessing IBD-related QOL impairments is feasible and effective. This mechanism is a promising tool for gastroenterologists to identify IBD patients at high risk of impaired QOL.Keywords: clinical research, artificial intelligence, model development, clinical decision support system

Beiying Deng,1,2,* Ying Chen,1,2,* Pengzhan He,1,2,* Yinghui Liu,3 Yangbo Li,1,2 Yuli Cai,4 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email dongweiguo@whu.edu.cnBackground: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes and diagnostic models with diagnostic potential.Methods: The gene expression profiles and clinical information of MASH patients and healthy controls were obtained from the Gene Expression Omnibus database (GEO). Limma and functional enrichment analysis were used to identify the mitophagy-related differentially expressed genes (mito-DEGs) in MASH patients. Machine learning models were used to select key mito-DEGs and evaluate their efficacy in the early diagnosis of MASH. The expression levels of the key mito-DEGs were validated using datasets and cell models. A nomogram was constructed to assess the risk of MASH progression based on the expression of the key mito-DEGs. The mitophagy-related molecular subtypes of MASH were evaluated.Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, and TIGAR were identified. Among the machine learning models employed, the Support Vector Machine demonstrated the highest AUC value of 0.935, while the Light Gradient Boosting model exhibited the highest accuracy (0.9189), kappa (0.7204), and F1-score (0.9508) values. Based on these models, MRAS, RAB7B, and RETREG1 were selected for further analysis. The logistic regression model based on these genes could accurately predict MASH diagnosis. The nomogram model based on these DEGs exhibited excellent prediction performance. The expression levels of the three mito-DEGs were validated in the independent datasets and cell models, and the results were found to be consistent with the findings obtained through bioinformatics analysis. Furthermore, our findings revealed significant differences in gene expression patterns, immune characteristics, biological functions, and enrichment pathways between the mitophagy-related molecular subtypes of MASH. Subtype-specific small-molecule drugs were identified using the CMap database.Conclusion: Our research provides novel insights into the role of mitophagy in MASH and uncovers novel targets for predictive and personalized MASH treatments.Keywords: metabolic dysfunction-associated steatohepatitis, mitophagy, biomarkers, diagnostic model, machine learning

Chen Yang,1,2,* Wangjun Dong,2,* Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128# Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Shina Song,1,2 Xiaofeng Li,1 Xuting Xue,3 Wenping Dong,2 Changxin Li1 1Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Geriatrics, General Hospital of TISCO, Taiyuan, People’s Republic of China; 3Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Wenping Dong, Department of Geriatrics, General Hospital of TISCO, North Street, Xinhualing District, Taiyuan, Shanxi Province, 030009, People’s Republic of China, Tel +86 13703581782, Email tgzyydwp@163.com Changxin Li, Department of Neurology, The First Hospital of Shanxi Medical University, Jiefangnan Road 85, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 13834635428, Email dslcxyx@126.comAbstract: High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1’s role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.Keywords: HTRA1, vascular anomalies, cerebral small vessel disease, AMD, tumor

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, #1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Xiajun Guo,* Sijia Wu,* Wanglin Dong, Yiqiu Zhang, Yue Su, Chaoran Chen Institute of Nursing and Health, School of Nursing and Health, Henan University, Kaifeng, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoran Chen, Email kfccr@126.comBackground & Aim: Non-suicidal self-injury (NSSI) in adolescents is a serious public health issue influenced by the interaction of multiple factors. The purpose of this study was to investigate the multiple mediating roles of alexithymia and self-esteem in the association between bullying victimization and NSSI in a sample of Chinese adolescents.Methods: A survey of 1299 adolescents from two public middle schools in Henan Province, China, was undertaken. Data were collected using the Chinese version of the Delaware bullying victimization scale-student (DBVS-S), the Toronto Alexithymia-20 Scale (TAS-20-C), the Rosenberg self-esteem scale (RSES), and the adolescent self-injury questionnaire. Besides, we performed a structural equation modeling (SEM) with latent variables using AMOS 26.0 to examine the relationship between variables and the mediating effects.Results: The SEM analysis found that not only can bullying victimization directly impact NSSI, but that alexithymia and self-esteem have a chain mediating effect in the association between bullying victimization and NSSI. This mediating effect contributed 22.47% to the total effect.Conclusion: These findings validate bullying victimization, alexithymia, and low self-esteem are important variables that affect NSSI among Chinese adolescents. Educators need to implement some prevention and intervention strategies to ameliorate the campus atmosphere and adolescents’ mental health aimed at avoiding NSSI behavior in adolescence.Keywords: bullying victimization, non-suicidal self-injury, alexithymia, self-esteem, adolescents

Zongbiao Tan,* Chuan Liu,* Pengzhan He,* Yanrui Wu, Jiao Li, Jixiang Zhang, Weiguo Dong Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cnPurpose: Immune infiltration plays a pivotal role in the pathogenesis of mucosal damage in ulcerative colitis (UC). The objective of this study was to systematically analyze and identify genetic characteristics associated with immune infiltration in UC.Patients and Methods: Gene expression data from three independent datasets obtained from the Gene Expression Omnibus (GEO) were utilized. By employing the ssGSEA and CIBERSORT algorithms, we estimated the extent of immune cell infiltration in UC samples. Subsequently, Weighted Correlation Network Analysis (WGCNA) was performed to identify gene modules exhibiting significant associations with immune infiltration, and further identification of hub genes associated with immune infiltration was accomplished using least absolute shrinkage and selection operator (LASSO) regression analysis. The relationship between the identified hub genes and clinical information was subsequently investigated.Results: Our findings revealed significant activation of both innate and adaptive immune cells in UC. Notably, the expression levels of CD44, IL1B, LYN, and ITGA5 displayed strong correlations with immune cell infiltration within the mucosa of UC patients. Immunohistochemical analysis confirmed the significant upregulation of CD44, LYN, and ITGA5 in UC samples, and their expression levels were found to be significantly associated with common inflammatory markers, including the systemic immune inflammation indices, C-reactive protein, and erythrocyte sedimentation rate.Conclusion: CD44, LYN, and ITGA5 are involved in the immune infiltration pathogenesis of UC and may be potential therapeutic targets for UC.Keywords: Ulcerative colitis, Immune infiltration, WGCNA, CIBERSORT, LASSO

Hanyu Fang,1,2 Tairan Dong,1 Shanlin Li,1 Yihan Zhang,1 Zhuojun Han,1 Mingfei Liu,1,2 Wenjun Dong,1,2 Zheng Hong,1,2 Min Fu,3 Hongchun Zhang1,2 1Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, 100029; 2Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 3Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of ChinaCorrespondence: Hongchun Zhang, Department of Traditional Chinese Medicine for Pulmonary Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +86 13701226664, Email 13701226664@139.com Min Fu, Department of Infectious Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100029, People’s Republic of China, Tel +86 13366093706, Email bdfumin@126.comObjective: Although studies on the association between COPD and lung cancer are of great significance, no bibliometric analysis has been conducted in the field of their comorbidity. This bibliometric analysis explores the current situation and frontier trends in the field of COPD and lung cancer comorbidity, and to lay a new direction for subsequent research.Methods: Articles in the field of COPD and cancer comorbidity were retrieved from Web of Science Core Collections (WoSCC) from 2004 to 2023, and analyzed by VOSviewer, CiteSpace, Biblimatrix and WPS Office.Results: In total, 3330 publications were included. The USA was the leading country with the most publications and great influence. The University of Groningen was the most productive institution. Edwin Kepner Silverman was the most influential scholar in this field. PLOS One was found to be the most prolific journal. Mechanisms and risk factors were of vital importance in this research field. Environmental pollution and pulmonary fibrosis may be future research prospects.Conclusion: This bibliometric analysis provided new guidance for the development of the field of COPD and lung cancer comorbidity by visualizing current research hotspots, and predicting possible hot research directions in the future.Keywords: COPD, lung cancer, bibliometric analysis, VOSviewer, CiteSpace

Aims: Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT. Methods: We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS). Results: All patients had ICRS grade IV cartilage lesions, except for one (ICRS grade III). The paired MOCART scores significantly improved from 42.5 (SD 1.53) to 63.5 (SD 22.60) (p = 0.025) in ten patients. Seven patients agreed to undergo second-look arthroscopy; 5 patients had grade I (normal) ICRS scores and two patients had grade II (nearly normal) ICRS scores. VAS, FFI, and all subscales of FAOS were significantly improved postoperatively (p ≤ 0.003). Conclusion: PACT significantly improved the clinical, radiological, and morphological outcomes of OLT. We consider this to be a safe and effective surgical method based on the short-term clinical results of this study. Cite this article: Bone Jt Open 2023;4(12):942–947.

Yuchen Gao,1,&ast; Chunrong Wang,2,&ast; Wenhao Dong,3 Bianfang Li,3 Jianhui Wang,1 Jun Li,1 Yu Tian,1 Jia Liu,1 Yuefu Wang3 1Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Surgical Intensive Care Unit & Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuefu Wang, Department of Surgical Intensive Care Unit & Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, People’s Republic of China, Email wangyuefu3806@bjsjth.cnBackground: To derive and validate a machine learning (ML) prediction model of acute kidney injury (AKI) that could be used for AKI surveillance and management to improve clinical outcomes.Methods: This retrospective cohort study was conducted in Fuwai Hospital, including patients aged 18 years and above undergoing cardiac surgery admitted between January 1, 2017, and December 31, 2018. Seventy percent of the observations were randomly selected for training and the remaining 30% for testing. The demographics, comorbidities, laboratory examination parameters, and operation details were used to construct a prediction model for AKI by logistic regression and eXtreme gradient boosting (Xgboost). The discrimination of each model was assessed on the test cohort by the area under the receiver operator characteristic (AUROC) curve, while calibration was performed by the calibration plot.Results: A total of 15,880 patients were enrolled in this study, and 4845 (30.5%) had developed AKI. Xgboost model had the higher discriminative ability compared with logistic regression (AUROC, 0.849 [95% CI, 0.837– 0.861] vs 0.803[95% CI 0.790– 0.817], P< 0.001) in the test dataset. The estimated glomerular filtration (eGFR) and creatine on intensive care unit (ICU) arrival are the two most important prediction parameters. A SHAP summary plot was used to illustrate the effects of the top 15 features attributed to the Xgboost model.Conclusion: ML models can provide clinical decision support to determine which patients should focus on perioperative preventive treatment to preemptively reduce acute kidney injury by predicting which patients are not at risk.Keywords: machine learning, acute kidney injury, cardiac surgery, shapley additive explanations, SHAP, prediction model

Zi-Qiang Li,1,&ast; Ye Qin,2,&ast; Wen-Peng Cai,1,&ast; Si-Qi Deng,3 Xiao-Fei Mao,1 Jian-Guo Zhang,1 Tian-Ya Hou,1 Yu Pan,4 Yi Cui,1 Ying-Nan Ge,5 Wei Dong,1,&ast; Yun-Xiang Tang1,&ast; 1Faculty of Psychology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The School of Mechanical Engineering, Changzhou University, Changzhou, 210046, People’s Republic of China; 3Department of Clinical Psychological Counseling, Shanghai Tongxinjici Health Couseling Center, Shanghai, 200433, People’s Republic of China; 4Department of Medical Psychology, Chinese PLA General Hospital, Beijing, 100830, People’s Republic of China; 5Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Dong; Yun-Xiang Tang, Faculty of Psychology, Naval Medical University, No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-13524435414 ; +86-13386271042, Email sophiedongwei@163.com; tangyun7633@sina.comPurpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm.Methods: A randomized pretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later.Results: Mean valence ratings of SD group were more negative than SC group’s (p < 0.05) and mean arousal ratings of SD group were higher than SC group’s (p < 0.01).Conclusion: Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation.Keywords: sleep deprivation, emotion regulation, cognitive reappraisal, IAPS, CRA

Qiuling Tong,1,2 Yu Yao,3 Yanhuo Xia,4 Zhibo Chen,2 Gangze Ji,2 Liuzhu Chen,2 Rujun Jin,2 Wanli Dong1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, Ningbo First Hospital, Ningbo, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Wanli Dong, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +8651265223637, Fax +8657755579318, Email wanlidong23@163.comObjective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA).Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann–Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test.Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores.Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.Keywords: migraine without aura, patent foramen ovale, clinical features, closure treatment

Abstract The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness of GBM cells in an NF-κB-inducing kinase (NIK)-dependent manner. While NIK activity is predominantly regulated at the posttranslational level, we show here that NIK (MAP3K14) is upregulated at the transcriptional level in invading cell populations, with the highest NIK expression observed in the most invasive cells. GBM cells with high induction of NIK gene expression demonstrate characteristics of collective invasion, facilitating invasion of neighboring cells. Furthermore, we demonstrate that the E2F transcription factors E2F4 and E2F5 directly regulate NIK transcription and are required to promote GBM cell invasion in response to TWEAK. Overall, our findings demonstrate that transcriptional induction of NIK facilitates collective cell migration and invasion, thereby promoting GBM pathogenesis.

Shuo Duan,1,&ast; Weijie Dong,2,&ast; Yichun Hua,3 Yali Zheng,4 Zengsuonan Ren,5 Guanmei Cao,6 Fangfang Wu,4 Tianhua Rong,1 Baoge Liu1 1Department of Orthopaedic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Medical Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 5Department of Orthopaedic Surgery, People’s Hospital of Hainan Tibetan Autonomous Prefecture, Hainan Tibetan Autonomous Prefecture, Qinghai Province, People’s Republic of China; 6Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoge Liu, Department of Orthopaedic Surgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 13581521066, Fax +010-59978702, Email baogeliu@hotmail.comPurpose: To explore the application of deep learning (DL) methods based on T2 sagittal MR images for discriminating between spinal tuberculosis (STB) and spinal metastases (SM).Patients and Methods: A total of 121 patients with histologically confirmed STB and SM across four institutions were retrospectively analyzed. Data from two institutions were used for developing deep learning models and internal validation, while the remaining institutions’ data were used for external testing. Utilizing MVITV2, EfficientNet-B3, ResNet101, and ResNet34 as backbone networks, we developed four distinct DL models and evaluated their diagnostic performance based on metrics such as accuracy (ACC), area under the receiver operating characteristic curve (AUC), F1 score, and confusion matrix. Furthermore, the external test images were blindly evaluated by two spine surgeons with different levels of experience. We also used Gradient-Class Activation Maps to visualize the high-dimensional features of different DL models.Results: For the internal validation set, MVITV2 outperformed other models with an accuracy of 98.7%, F1 score of 98.6%, and AUC of 0.98. Other models followed in this order: EfficientNet-B3 (ACC: 96.1%, F1 score: 95.9%, AUC: 0.99), ResNet101 (ACC: 85.5%, F1 score: 84.8%, AUC: 0.90), and ResNet34 (ACC: 81.6%, F1 score: 80.7%, AUC: 0.85). For the external test set, MVITV2 again performed excellently with an accuracy of 91.9%, F1 score of 91.5%, and an AUC of 0.95. EfficientNet-B3 came second (ACC: 85.9, F1 score: 91.5%, AUC: 0.91), followed by ResNet101 (ACC:80.8, F1 score: 80.0%, AUC: 0.87) and ResNet34 (ACC: 78.8, F1 score: 77.9%, AUC: 0.86). Additionally, the diagnostic accuracy of the less experienced spine surgeon was 73.7%, while that of the more experienced surgeon was 88.9%.Conclusion: Deep learning based on T2WI sagittal images can help discriminate between STB and SM, and can achieve a level of diagnostic performance comparable with that produced by experienced spine surgeons.Keywords: artificial intelligence, deep learning, spinal tuberculosis, spinal metastases, magnetic resonance imaging

Wanyang Dong,1,&ast; Qi Peng,1,&ast; Xiaohua Tang,1,2,&ast; Tian Zhong,1 Shunan Lin,1 Ziling Zhi,1 Jingyi Ye,1 Bixia Yang,1 Ning Sun,1,3 Wenchang Yuan1 1Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510180, People’s Republic of China; 2Third Affiliated Hospital of Guangzhou Medical University, Department of Clinical Laboratory, Guangzhou, 510150, People’s Republic of China; 3Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Sun; Wenchang Yuan, Email ning.sun@connect.polyu.hk; yuanwenchang95@163.comBackground: Staphylococcus haemolyticus is an opportunistic pathogen that belongs to coagulase-negative Staphylococci (CoNS). Increasing infection and multi-drug resistance cases caused by this strain have been reported and thus it poses a great health threat.Methods: The third-generation sequencing technology was performed on a S. haemolyticus SH-1 isolated from a clinical sample to analyze the drug resistance genes, which included vancomycin resistance related genes. In addition, antimicrobial susceptibility tests, transmission electron microscopy and Triton X-100 stimulated autolysis were conducted to understand its biological characteristics.Results: The study shows that this clinical isolate is a vancomycin intermediate-resistant strain. Genome comparison also revealed that WalK(N70K) and WalK(R280Q) mutations may contribute to the vancomycin resistant phenotype. Besides, S. haemolyticus SH-1 exhibit common features of thicker cell wall and decreased autolytic activity.Conclusion: S. haemolyticus SH-1 with WalKR mutations shows typical characteristics of vancomycin resistant strains. Combining the genome features and biological properties, our findings may provide important information for the understanding of the molecular mechanism of S. haemolyticus to vancomycin intermediate-resistance.Keywords: Staphylococcus haemolyticus, drug resistance gene, vancomycin intermediate-resistance, whole genome sequencing

Rong Yu,1,&ast; Chuan Liu,1,&ast; Jixiang Zhang,1,&ast; Jiao Li,1,&ast; Shan Tian,2 Fugui Ding,1 Zhengru Liu,3 Ting Wang,4 Zhongchun Liu,5 Changqing Jiang,6 Jie Shi,7 Kaichun Wu,8 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 4Department of Gastroenterology, First Affiliated Hospital of Hainan Medical College, Haikou, 570102, People’s Republic of China; 5Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 7Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 8Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cn Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, No. 127 West Changle Road, Xi’an, Shaanxi Province, 710032, People’s Republic of China, Tel +86 029-84771600, Email kaicwu@fmmu.edu.cnObjective: To explore the correlation between disease activity and anxiety, depression, sleep quality, and quality of life in patients with inflammatory bowel disease (IBD).Methods: The disease activity of IBD patients was evaluated by 66 gastroenterologists from 42 hospitals in 22 provinces in China from September 2021 to May 2022. Anxiety, depression, sleep quality and quality of life of IBD patients were investigated and statistically analyzed by different scales, including Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Quality-of-Life Questionnaire (IBD-Q).Results: A total of 2478 IBD patients were included, of which 1532 (61.8%) were in active stage and 946 (38.2%) were in remission. The proportions of active IBD with anxiety, depression, sleep disturbance, and poor quality of life were 29.5%, 29.7%, 71.1%, and 50.1%, respectively, while the proportions of remission IBD with anxiety, depression, sleep disturbance, and poor quality of life were 19.1%, 24.4%, 69.3%, and 17.4%, respectively. IBD patients who also had anxiety, depression, sleep disturbances and poor quality of life had 80 cases (8.46%) in remission and 114 cases (7.44%) in active stage, with 54 cases (9.18%) in mild activity, 51 cases (6.95%) in moderate activity and 9 cases (4.49%) in severe activity. IBD patients with different disease activity levels differed in GAD-7 scores, PHQ-9 scores, PSQI scores, and IBD-Q scores (all P< 0.001). In IBD patients, anxiety, depression, and sleep disturbance, which interact with each other, can further aggravate their disease activity (all P< 0.001).Conclusion: Anxiety, depression, sleep disturbances, and quality of life are strongly correlated with disease activity in IBD patients, and IBD patients with psychological disturbances are most often in the active stage and have a poor quality of life.Keywords: inflammatory bowel disease, disease activity, anxiety, depression, sleep quality, quality of life, survey

Jiankang Xiang,1 Jiao Li,1 Chuan Liu,1 Shan Tian,2 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Weiguo Dong, Email dongweiguo@whu.edu.cnAim: The differences of clinical characteristics stratified by age at diagnosis especially according to Montreal classification were rarely studied in China. This study aimed to evaluate and compare the clinical features in various groups of CD patients stratified by age at diagnosis.Methods: A cross-sectional study of CD patients was conducted through a stratified sampling according to Montreal classification. Patients were divided into three groups by age at diagnosis: group A1 (< 17 years old), group A2 (17 to 40 years old), and group A3 (> 40 years old). The clinical characteristics, laboratory tests, radiographic, and endoscopic features were analyzed by statistics.Results: We enrolled 259 CD patients for the study. There was male predominance under 40 years old. Compared to group A1, more female patients were presented in group A3. There were more patients had perianal fistulas in group A1 compared to group A2 and group A3. Compared with group A1, patients in group A2 were associated with lower total protein (TP) levels. The mean TP and platelet count (PC) levels in group A3 were lower than group A1. Patients in group A1 had a lower rate of stricturing (B2) disease behavior than group A2 and group A3, and patients in group A3 who had a B2 disease behavior were higher than group A2. Those differences could guide early treatment or inventions for CD patients who might progress to a more complex disease behavior.Conclusion: CD patients stratified by age at diagnosis according to Montreal classification had different clinical symptoms, laboratory test results as well as disease locations and behaviors.Keywords: Crohn’s disease, age at diagnosis, Montreal classification, clinical characteristics

Shuang Zhang,1,2 Nan Li,1 Weiqin Li,1 Leishen Wang,1 Enqing Liu,1 Tao Zhang,1 Wei Dong,1 Jiujing Chen,2 Junhong Leng1 1Tianjin Women’s and Children’s Health Center, Tianjin, People’s Republic of China; 2NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Junhong Leng, Email ljhlzqljhlzq@163.comObjective: We aim to investigate the influence of weight gain during pregnancy on the risk of offspring adiposity before five years old.Methods: We retrospectively collected health information from the Tianjin mother-child cohort. Offspring outcome was BMI Z-score and prevalence of childhood adiposity from 0.5– 5 years old. Gestational weight gain was analyzed using continuous and categorical variables evaluated by the IOM guidelines. Multivariate analysis adjusted maternal age, prepregnancy BMI, maternal height, smoking, cesarean section, gestational age at birth, birth weight, birth length, and mode of infant feeding during 0– 6 months.Results: Gestational weight gain contributed to offspring’s BMI Z-score from 1– 5 years old, and the effect was most obvious in the first half of pregnancy (multivariate analysis, at 1, 2, 2.5, 3, 4, and 5 years of age: β 0.011, 95% CI 0.008– 0.014; β 0.017, 95% CI 0.015– 0.020; β 0.005, 95%CI 0.002-0.008; β 0.018, 95% CI 0.015– 0.021; β 0.014, 95% CI 0.009– 0.020; β 0.013, 95% CI 0.005– 0.021). Excessive weight gain was associated with a higher prevalence of offspring adiposity before five years, even if prepregnancy BMI is normal. Multivariate regression analysis further confirmed that excessive weight gain during the first half of pregnancy significantly increased the risk of childhood obesity at aged one and three (AOR 1.083, 95% CI 1.003– 1.169; AOR 1.158, 95% CI 1.036– 1.293).Conclusion: Offspring have a higher risk of preschool adiposity when gestational weight gain was excessive during the first half of pregnancy.Keywords: gestational weight gain, the first half of pregnancy, childhood obesity, retrospective cohort study

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Ruhai Bai,1 Jianmin Gao,2 Wanyue Dong3 1School of Public Affairs, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 2School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Wanyue Dong, School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel +86 25 858 11301, Email wanyuedong@njucm.edu.cnPurpose: Northwest China has a large area, low population density, and few health resources, which makes the utilization of health resources in this region difficult. The objective of this study was to assess utilization of health services and its association with travel time in Shaanxi Province.Patients and Methods: Data were obtained from the fifth Household Health Service Survey of Shaanxi Province conducted in 2013. Binary logistic regression was used to assess the relationship between travel time and health service utilization, and negative binomial regression was conducted to assess the relationship between travel time and the frequency of health service utilization.Results: A total of 42.6% of patients used health services, with a higher use rate among rural residents than among urban residents (47.0% and 27.4%, respectively). A total of 30.9% of patients traveled more than 15 min to the nearest medical facility (33.3% in rural areas and 22.6% in urban areas). A total of 12.4% of patients traveled more than 30 min to the nearest medical facility (15.1% in rural areas and 3.0% in urban areas). Urban residents living farthest from health care facilities (more than 30 min) had a 2.12-fold higher probability of health service utilization and expected to have a health service utilization rate 1.77 times greater than that of residents with a travel time of less than 5 min. Among the rural population, there was no significant correlation between travel time and health service utilization.Conclusion: Urban patients living farthest from hospitals were more likely to use health services and used health services more frequently. This suggests that more attention should be given to urban patients who live far away from health service providers in Shaanxi Province.Keywords: health equity, accessibility, travel time, health service utilization

Lisha Chi,1,&ast; Guojing Zhao,2,&ast; Naiche Chen,3,&ast; Guanghui Shen,4 Kai Huang,4 Xiaoyu Xia,1 Yijing Chen,1 Jian Liu,1 Ran Xu,5 Yanhan Chen,6 Weijie Dong,7 Jiexia Zheng8 1School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Institute of China Innovation and Entrepreneurship Education, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Renji College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Natural Science, Affiliated School of Wenzhou University Town, Wenzhou, People’s Republic of China; 6School of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7The 1th School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 8Department of Student Affairs, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiexia ZhengDepartment of Student Affairs, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaEmail zhengjiexia2021@163.comBackground: Vaccination is an effective strategy to mitigate the spread of COVID-19. This study aimed to compare predictors of vaccination intention between healthcare workers (HCWs) and non-healthcare workers (non-HCWs) in China.Methods: A web-based cross-sectional survey was conducted among HCWs and non-HCWs. Several bivariate analysis techniques, eg, crosstab with Chi-square, independent t-test and single factor ANOVA, were performed to analyze the correlation. After that, a series of multivariate binary regressions were employed to determine predictors of vaccination intention.Results: Intention was closely and significantly related with gender, perceived vaccination knowledge, perceived importance and effectiveness of vaccine to prevent COVID-19. HCWs and non-HCWs were heterogeneous, since vaccination intention, perceived knowledge, and attitudes (eg, importance, severity, risk) toward COVID-19 or vaccine had statistically significant difference between the two groups. With comparison of predictors of vaccination intention, for HCWs, demographic factors were the major predictors of COVID-19 vaccination intention. Female HCWs and HCWs with a Master’s or higher degree were more hesitant about vaccination (P = 0.01 and P < 0.001, respectively), while HCWs had greater vaccination intention as their age increased (P = 0.02). For non-HCWs, perceived vaccination knowledge was the major predictor of COVID-19 vaccination intention (P < 0.001). Additionally, perceived importance and effectiveness of vaccine were predictors for both HCWs and non-HCWs.Conclusion: Vaccination intention of HCWs was greater than that of non-HCWs in China. Measures should be taken to improve the vaccination rate based on the predictors of vaccination intention identified in this study. For HCWs, especially those with a high level of education or who were females, the safety and effectiveness of vaccines in use may reinforce their vaccination intention. For non-HCWs, popularization of general medical knowledge, including of vaccine-preventable diseases, may increase their vaccination intention.Keywords: COVID-19 vaccine, intention, predictor, HCWs, non-HCWs

Ruhai Bai,1 Wanyue Dong,2 Jinli Liu,3 Qiao Peng,3 Jun Lyu4 1School of Public Affairs, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Jun LyuDepartment of Clinical Research, The First Affiliated Hospital of Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of ChinaEmail lyujun2020@jnu.edu.cnPurpose: The Belt and Road Initiative (BRI) provided a platform to promote trade and economic collaboration, with health promotion also being an important component. This study examined the burden of the under-5 mortality rate (U5MR) among BRI countries and studied the impact of socioeconomic development on the U5MR.Patients and Methods: Data were collected from 137 BRI countries for the period 2000– 2018. The temporal changes in the U5MR and the estimated annual percentage change (EAPC) were used to assess the U5MR burden. A quantile fixed-effects model was used to access the associations between socioeconomic factors and the U5MR.Results: The U5MR varied widely among the 137 analyzed countries in 2018, being highest in Somalia (121.5 per 1000) and lowest in Slovenia (2.1 per 1000). The decreasing trend in U5MR was largest in Montenegro (EAPC = – 9.6, 95% confidence interval [CI] = – 10.2 to – 9.0), while the increasing trend was largest in Dominica (EAPC = 6.0, 95% CI = 5.3 to 6.7). Countries with higher U5MRs in 2000 experienced more rapid decreases in the U5MR from 2000 to 2018. The influence of socioeconomic factors on U5MR was related to the distribution of U5MR.Conclusion: The U5MR remains a major public-health issue in some BRI countries. Improving the economic situation will benefit child health in BRI countries in the long run.Keywords: Belt and Road, under-five mortality rate, socioeconomic, economic factors

Baoya Wang,1 Wenjuan Dong,2 Liyan Ma,3 Yonghui Dong,4 Shanmei Wang,1 Youhua Yuan,1 Qiong Ma,1 Junhong Xu,1 Wenjuan Yan,1 Jing Nan,1 Qi Zhang,1 Wenbo Xu,1 Bing Ma,1 Yafei Chu,1 Jiangfeng Zhang,1 Li Li,1 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of China; 2Department of Clinical Microbiology, Xicheng District Pingan Hospital, Beijing, 100035, People’s Republic of China; 3Department of Clinical Microbiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 4Department of Osteology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Yi Li; Li LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 5, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +8637165580484Fax +8637187160318Email liyilabmed@henu.edu.cn; hnykylili@126.comObjective: This study aimed to investigate the prevalence, genetic diversity and clinical characteristics of Clostridium perfringens isolates from hospitalized clinical diarrheal patients.Methods: A prospective study was conducted on 1108 patients with diarrhea during hospitalization. Stool samples were cultured for C. perfringens, and the toxin genes were detected by PCR. The available clinical data of 112 patients were analyzed to study the clinical features of various isolates. Multi-locus sequence typing (MLST) was performed to assess phylogenetic relationship between different isolates.Results: A total of 153 (13.8%) isolates were obtained from patients’ stools. C. perfringens type F (49.0%) was the major toxin type in the isolates, followed by type A (n = 59, 38.6%) and type C (n = 14, 9.2%). Patients older than 50 years and those with underlying diseases of cancer, hepatobiliary system, and ulcerative colitis (UC) were more predisposed to C. perfringens type F and type A infection than to type C. The patients infected with type C experienced more severe clinical symptoms compared to those with type A infection. There was a significant association between type FC and foodborne gastrointestinal (GI) diseases (p = 0.018), between type FP and antibiotic-associated diarrhea (AAD) (p < 0.001), and between type A and sporadic diarrhea (SD) (p < 0.001). Phylogenetic analysis indicated that type F isolates carrying a chromosomal cpe gene mainly belonged to ST77 (6/15 isolates). Type F isolates with cpe gene on a plasmid exhibited high genetic diversity.Conclusion: High prevalence and considerable genetic diversity of C. perfringens type F were found in clinical diarrheal patients. Elderly people and patients with cancer, hepatobiliary diseases or UC, or suspected of having food poisoning (FP) may be targeted for routine testing of C. perfringens toxin genes and may benefit from early detection of C. perfringens type C isolates that cause more severe clinical symptoms.Keywords: Clostridium perfringens, toxin type, clinical characteristics, prevalence, MLST

Changlin Mao,1 Wei Dong,2 Jiaju Lu,3 Zhao Zhang,4 Hongliang Wu,5 Armin Ghavamian,1 Dongbin Bi,3 Pei Gao,1 Zhao Liu,5 Sentai Ding1,3 1Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Urology, Shandong Provincial Hospital West Branch, Jinan, Shandong, 250000, People’s Republic of China; 3Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 5Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Zhao LiuDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail zhao.liu@sdu.edu.cnSentai DingDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail dingsentai@126.comObjective: Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa.Methods: Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson’s χ 2 test and Fisher’s exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan–Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients.Results: βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa.Conclusion: βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.Keywords: FGFR, biomarker, prostate cancer, survival

Zhicheng Song,1,2,* Wenpei Dong,1,2,* Dongchao Yang,2 Jianjun Yang,2 Jugang Wu,2 Yiping Wang,2 Yan Gu1,2 1Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan GuDepartment of General Surgery, Huadong Hospital, Fudan University, No. 221 West Yan’an Road, Shanghai, 200040, People’s Republic of ChinaEmail yangu@shsmu.edu.cnPurpose: To explore the value of medical three-dimensional visualization technology in precise preoperative assessment of complex abdominal wall defects.Methods: The clinical data of 30 patients were analyzed retrospectively from November 2017 to December 2020 in our department. Ten patients had abdominal wall hernias and 20 patients suffered from abdominal wall tumors. CT examination was performed, and data were stored in the form of DICOM. Three-dimensional reconstruction and related data analysis were performed by Medraw software, which can accurately show the calculation of the abdominal wall defect area, abdominal wall defect classification and zoning.Results: The ratio of the volume of the hernia sac to the whole abdominal volume in 10 patients with abdominal wall hernia was 4.75%. The average ratio of defect area to the whole abdominal wall in 16 patients suffered from abdominal wall tumors was 17.68%. Preoperative three-dimensional reconstruction can accurately obtain an average abdominal wall defect area of 227.83 ± 157.33 cm2 and accurate abdominal wall classification and zoning. Combined with clinical information, we can develop personalized surgical plans for patients. The average operating time was 5.39 ± 2.71 h, respectively, and the average hospital stay was 22.77 ± 11.59 days. The mean follow-up time was 21.09 ± 9.72 months. The incidence of postoperative complications was 23.33% (7/30). The recurrence rates of incisional hernias and abdominal wall tumors were 20.00% (2/10) and 15.00% (3/20), respectively. The patient survival rate was 86.67% (26/30).Conclusion: Three-dimensional visualization technology can be used for the accurate evaluation of patients with complex abdominal defects before surgery and can help surgeons design personalized surgical plans for patients.Keywords: three-dimensional visualization, complex abdominal wall defects, abdominal wall tumor, abdominal wall reconstruction

Xufeng Guo,1 Shan Tian,2 Pan Cao,3 Yishan Xie,1 Weiguo Dong2 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Infectious Disease, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Weiguo DongDepartment of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, People’s Republic of ChinaTel +86-027-88041911Email Ddongweiguo@163.comCorrespondence: Yishan XieDepartment of Oncology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, People’s Republic of ChinaTel +86-027-88041911Email 18502753963@163.comPurpose: The effects of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC), in the progression of liver cancer are unknown. In this study, we attempted to clarify the clinical significance and mechanism of PIGC in hepatocellular carcinoma (HCC).Patients and Methods: To explore the expression profiles, DNA methylation, mutation status, clinical relevance, and prognostic value of PIGC in patients with HCC, a series of bioinformatic databases and websites were searched. Moreover, numerous vitro experiments were performed to investigate the mechanism of PIGC in the regulation of cancerous liver cells.Results: Expression of PIGC mRNA and protein was upregulated in cancerous liver specimens compared with normal liver tissues. High expression of PIGC mRNA was related to higher tumor grade, lymphatic metastasis, advanced TNM stage, and TP53 mutation. High expression of PIGC mRNA predicted more unfavorable overall survival (OS) (HR=1.7, P=0.0028) and disease-free survival (DFS) (HR=1.5, P=0.0067) in patients with liver cancer. The mutation rate of PIGC was 10%, and amplification was the most common mutant type. Expression of PIGC mRNA was negatively regulated by its DNA methylation (r=− 0.398, P< 0.0001). Moreover, silencing of PIGC in HepG2 cell line inhibited the proliferation and migration and led to cell cycle arrest at G0/G1 stage by reducing cyclinD1, CDK2, CDK4, and CDK6 expression, while overexpression of PIGC in Hcclm3 cell line revealed the opposite effect.Conclusion: PIGC is related to aggressive clinical features, and overexpression of PIGC signifies worse survival in patients with HCC. PIGC promotes proliferation and migration of cancerous liver cells through the regulation of the cell cycle.Keywords: hepatocellular carcinoma, PIGC, gene mutation, survival, cell cycle

Xikun Wu,1 Weichong Dong,1 Haoran Li,1 Xiuling Yang,1 Yiran Jin,1 Zhiqing Zhang,1 Ye Jiang2 1The Second Hospital of Hebei Medical University, Shijiazhuang City, People’s Republic of China; 2Pharmacy College, Hebei Medical University, Shijiazhuang City, People’s Republic of ChinaCorrespondence: Zhiqing ZhangThe Second Hospital of Hebei Medical University, Department of Pharmacy, 215 Hepingxi Road, Shijiazhuang City, 050000, People’s Republic of ChinaEmail 777yyy@sina.cnYe JiangPharmacy College, Hebei Medical University, 361 Zhangshandong Road, Shijiazhuang City, 050017, People’s Republic of ChinaEmail jiangye@hebmu.edu.cnPurpose: To perform therapeutic drug monitoring (TDM) of total and free plasma valproic acid (VPA) concentrations in pediatric patients with epilepsy and to analyze related factors.Patients and Methods: Pediatric epileptic patients treated in 2015– 2019 in our hospital were assessed. Total and free plasma VPA concentrations were obtained by UPLC and LC-MS/MS, respectively. Regression analysis was performed to examine the associations of free plasma VPA with total plasma VPA and plasma protein binding rate. The impacts of individual situation, CYP2C9 genotype, and drug combination on VPA concentration were examined.Results: Of the 251 patients, 81 had lower total concentrations than effective therapeutic levels; 86 and 31 patients had infections and central nervous system dysplasia, respectively. VPA’s daily doses and free drug concentrations were significantly lower in the CYP2C9 *3/*3 genotype group versus the CYP2C9 *1/*3 and CYP2C9 *1/*1 groups (P< 0.05). Free and total VPA concentrations were linked by Y = 0.0004 X2 + 0.042 X + 0.3035 (r=0.6981); VPA plasma protein binding rate and free VPA concentration were related by Y = 0.0003 X2 - 0.0127 X + 0.9777 (r=0.8136). Both total and free VPA concentrations were significantly decreased in patients simultaneously administered phenobarbital, meropenem and biapenem (P< 0.05), with therapeutic failure after meropenem/biapenem co-administration.Conclusion: Free VPA amounts have nonlinear relationships with total VPA amounts and plasma protein binding rate in epileptic children. Additionally, CYP2C9 *3/*3 expression affects VPA metabolism. Since phenobarbital affects VPA metabolism, TDM is recommended. Meanwhile, carbapenem-co-administration with VPA should be prohibited.Keywords: valproic acid, pediatric patient, free concentration, CYP2C9 gene expression, TDM

Abstract Cancers, including glioblastoma multiforme (GBM), undergo coordinated reprogramming of metabolic pathways that control glycolysis and oxidative phosphorylation (OXPHOS) to promote tumor growth in diverse tumor microenvironments. Adaptation to limited nutrient availability in the microenvironment is associated with remodeling of mitochondrial morphology and bioenergetic capacity. We recently demonstrated that NF-κB-inducing kinase (NIK) regulates mitochondrial morphology to promote GBM cell invasion. Here, we show that NIK is recruited to the outer membrane of dividing mitochondria with the master fission regulator, Dynamin-related protein1 (DRP1). Moreover, glucose deprivation-mediated metabolic shift to OXPHOS increases fission and mitochondrial localization of both NIK and DRP1. NIK deficiency results in decreased mitochondrial respiration, ATP production, and spare respiratory capacity (SRC), a critical measure of mitochondrial fitness. Although IκB kinase α and β (IKKα/β) and NIK are required for OXPHOS in high glucose media, only NIK is required to increase SRC under glucose deprivation. Consistent with an IKK-independent role for NIK in regulating metabolism, we show that NIK phosphorylates DRP1-S616 in vitro and in vivo. Notably, a constitutively active DRP1-S616E mutant rescues oxidative metabolism, invasiveness, and tumorigenic potential in NIK−/− cells without inducing IKK. Thus, we establish that NIK is critical for bioenergetic stress responses to promote GBM cell pathogenesis independently of IKK. Our data suggest that targeting NIK may be used to exploit metabolic vulnerabilities and improve therapeutic strategies for GBM.

Ruhai Bai,1,2 Wentao Wu,3 Wanyue Dong,3,4 Jinli Liu,3 Lili Yang,5 Jun Lyu1 1Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Evidence-Based Research Center of Social Science & Health, Public Affair School of Nanjing University of Science & Technology, Nanjing, People’s Republic of China; 3School of Public Health, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4School of Health Economics and Management, Nanjing Chinese Medicine University, Nanjing, People’s Republic of China; 5Department of General Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Jun LyuJinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of ChinaEmail lyujun2020@jnu.edu.cnPurpose: The objective of this study was to forecast the prevalence rates and the populations of overweight and obese in Chinese adults for 2030.Materials and Methods: Nine waves of China Health and Nutrition Survey (CHNS) data from 1991 to 2015 were used. A polynomial regression model was fitted to obtain the average BMI change trajectory of the population born in different years according to different sexes and residence areas (urban and rural). The model fitted to CHNS 2015 survey data was used to forecast the distribution of BMI and the prevalence rates of overweight and obesity in 15 years. The United Nations population forecast was then used to predict the proportions of overweight obese adults in all age groups in China in 2030.Results: The prevalence rates of overweight and obesity were projected to increase in both sexes and all geographic areas in future. By 2030, urban males will have the highest prevalence of overweight, 50.7% (95% CI: 47.5%, 53.9%). Except urban males, the prevalence of overweight and obesity in rural areas will exceed that in urban for both sexes. In 2030, the numbers of overweight and obese people in China aged 20– 89 years will reach 540 million and 150 million, respectively, which are 2.8 and 7.5 times higher compared to prevalences in 2000. In 2030, the number of overweight and obese people in China aged 60– 89 years will reach 200 million and 40 million, respectively, 6.3 and 8.5 times increments from the year 2000.Conclusion: The prevalence rates of overweight and obese in Chinese adults are projected to increase further, by 2030 more than half of adult males living in urban areas will be overweight. Combined with changes in the population age structure, overweight and obesity will have a huge impact on the health of the Chinese population over the next 15 years.Keywords: aging, BMI, prediction, population; overweight; obesity

Shubin Wang,1,* Juan An,2,* Weiwei Dong,3,* Xin Wang,4 Jianqiu Sheng,4 Yan Jia,4 Yuqi He,4 Xianzong Ma,4 Jiheng Wang,4 Dedong Yu,1 Xiuqin Jia,1 Bingyu Wang,5 Wenbo Yu,5 Kejia Liu,5 Yuanyuan Zhao,6 Yun Wu,1 Wei Zhu,1 Yuanming Pan1,4,6 1Department of Oncology, Baotou City Central Hospital, Baotou 014040, People’s Republic of China; 2Department of Basic Research Medical Sciences, Qinghai University, Xining 810001, People’s Republic of China; 3Department of Oncology, General Hospital of Chinese People’s Liberation Army, Beijing 100085, People’s Republic of China; 4Department of Gastroenterology, The 7th Medical Center of Chinese PLA General Hospital, Beijing 100700, People’s Republic of China; 5Yidu Cloud (Beijing) Technology Co. Ltd 8F, Health Work, Beijing 100083, People’s Republic of China; 6National Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanming PanNational Center for Nanoscience and Technology, Zhongguancun, Beijing 100190, People’s Republic of ChinaTel +86-10-6406-9831Fax +86-10-6401-2266Email panym@nanoctr.cnWei ZhuDepartment of Oncology, Baotou City Central Hospital, Baotou, Inner Mongolia 01404, People’s Republic of ChinaTel +86-472-6955473Fax +86-472-6955708Email 18686111667@163.comIntroduction: Glioma is the primary malignant brain tumor with poor prognosis. Berberine (BBR) was the potential drug for anti-tumor in glioma cells. Based on its limitation of poor aqueous solubility and instability, little information of BBR nanoparticles is reported in glioma.Methods: Different solutions including 5% glucose, 1*PBS, ddH2O, 0.9% NaCl, cell culture medium were selected, and only 5% glucose and ddH2O exhibited BBR-related nanoparticles. After heating for a longer time or adding a higher concentration of glucose solution, BBR nanoparticles were detected by TEM analysis. The uptake of BBR-Glu or BBR-Water nanoparticles were detected by immunofluorescence analysis for BBR autofluorescence. Cell viability was measured by MTT assay and Western blotting analysis. Apoptosis was performed with flow cytometric analysis and was detected by cleaved caspase-3 immuno-fluorescent staining. Cell cycle was used by flow cytometric analysis. Cytoskeleton was observed by confocal analysis using the neuron specific Class III ß-tubulin and ß-tubulin antibodies. Mitochondrial-related proteins were detected by Western blotting analyses and mito-tracker staining in live cells. Mitochondrion structures were observed by TEM analysis. ROS generation and ATP production were detected by related commercial kits. The tracking of BBR-Glu or BBR-Water nanoparticles into blood–brain barrier was observed in primary tumor-bearing models. The fluorescence of BBR was detected by confocal analyses in brains and gliomas.Results: BBR-Glu nanoparticles became more homogenized and smaller with dose- and time-dependent manners. BBR-Glu nanoparticles were easily absorbed in glioma cells. The IC50 of BBR-Glu in U87 and U251 was far lower than that of BBR-Water. BBR-Glu performed better cytotoxicity, with higher G2/M phase arrest, decreased cell viability by targeting mitochondrion. In primary U87 glioma-bearing mice, BBR-Glu exhibited better imaging in brains and gliomas, indicating that more BBR moved across the blood–brain tumor barrier.Discussion: BBR-Glu nanoparticles have better solubility and stability, providing a promising strategy in glioma precision treatment.Keywords: berberine, glioma, glucose-nanocarrier, nanoparticles, mitochondria

Weimin Dong,1 Yong Luo,2 Guian Zhang,1 Hui Zhang,1 Yuxiang Liang,1 Yangjia Zhuo,1 Yingke Liang,1 Fen Zou,1 Weide Zhong1,3,4 1Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, People’s Republic of China; 2Department of Urology, The Second People’s Hospital of Foshan, Affiliated Foshan Hospital of Southern Medical University, Foshan 528000, People’s Republic of China; 3Department of Urology, Huadu District People’s Hospital, Southern Medical University, Guangzhou 510800, People’s Republic of China; 4Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, People’s Republic of ChinaCorrespondence: Weide Zhong; Fen ZouDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of ChinaTel +86 20-81048312Fax +86 20-8337332Email zhongwd2009@live.cn; zoufen2008@126.comIntroduction: Although carbon nanospheres (CNPs) are promising nanomaterials in cancer treatment, how they affect prostate cancer (PCa) remains unclear.Methods: In this study, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy were used to confirm the successful synthesis of CNPs. CCK-8, flow cytometry, Transwell, wound healing, Western blot and immunohistochemistry (IHC) assays were performed to evaluate the antitumor effect of CNPs toward the two kinds of prostate cancer cell lines PC3 and DU145.Results: Our results showed that CNPs inhibited cell growth, invasion, and migration and induced apoptosis and autophagy in PCa cells. Multifactor detection of a single Akt phosphorylation pathway and Western blot results suggested the suppression of 4E-BP1 in PCa cells after incubation with CNPs. The results from animal experiments also suggested the antitumor effect of CNPs and reduced 4E-BP1 expression in PCa tissue samples from BALB/c nude mice administered a local subcutaneous injection of CNPs.Keywords: carbon nanosphere, prostate cancer, antitumor, 4E-BP1

Wujun Dong1,2 ,* Jun Ye1,2 ,* Weijue Wang,1,2 Yanfang Yang,1,2 Hongliang Wang,1,2 Tong Sun,1,2 Lili Gao,1,2 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuling LiuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of ChinaTel +86 10 89285188Fax +86 10 89285190Email ylliu@imm.ac.cnPurpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein.Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein.Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation.Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.Keywords: lecithin/chitosan nanoparticles, transdermal delivery, phospholipid complex, baicalein

Introduction: Post-contrast acute kidney injury (PC-AKI) develops in a significant proportion of patients with CKD after invasive cardiology procedures and is strongly associated with adverse outcomes. Objective: We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. Methods: To create a large animal model of CKD, we infused 250 micron particles into the renal arteries in 56 ± 8 kg pigs. We used a low-frequency therapeutic ultrasound device (LOTUS – 29 kHz, 0.4 W/cm2) to induce NO release. NO and laser Doppler probes were used to assess changes in NO content and blood flow. Glomerular filtration rate (GFR) was measured by technetium-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) radionuclide imaging. PC-AKI was induced by intravenous infusion of 7 cm3/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m--DTPA radionuclide imaging. Results: In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2–2.6 ± 0.9, p < 0.01, n = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (p = 0.016, n = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, p < 0.01, n = 3). LOTUS (starting 15 min prior to contrast and lasting for 90 min) prevented PC-AKI in the same animals 1 week later (Cr 2.5 ± 0.4 baseline to 2.6 ± 0.7 at 24 h, p = ns, n = 3). In patients with CKD (n = 10), there was an overall 25% increase in GFR in response to LOTUS (p < 0.01). Conclusions: LOTUS increased intrarenal NO, RBF, and GFR and prevented PC-AKI in a large animal model of CKD, and significantly increased GFR in patients with CKD. This novel approach may provide a noninvasive nonpharmacological means to prevent PC-AKI in high-risk patients.

Wei Dong,1,2,* Hua Yu,1,2,* Yu-Yao Zhu,1,2,* Zhi-Hong Xian,1,2 Jia Chen,1,2 Hao Wang,3 Chun-Chao Shi,4 Guang-Zhi Jin,5 Hui Dong,1,2 Wen-Ming Cong1,2 1Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People’s Republic of China; 2Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People’s Republic of China; 3Department of Hepatobiliary Diseases, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People’s Republic of China; 4Second Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, People’s Republic of China; 5Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui DongDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, People’s Republic of ChinaEmail 13917078308@126.comWen-Ming CongDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, People’s Republic of ChinaEmail wmcong@smmu.edu.cnPurpose: This study aimed to propose an effective quantitative pathological scoring system and to establish nomogram to assess the stage of cirrhosis and predict postoperative survival of hepatocellular carcinoma (HCC) with cirrhosis patients after hepatectomy.Methods: The scoring system was based on a retrospective study on 163 patients who underwent partial hepatectomy for HCC with cirrhosis. The clinicopathological and follow-up data of 163 HCC with cirrhosis patients who underwent hepatectomy in our hospital from 2010 to 2014 were retrospectively reviewed. A scoring system was established based on the total value of independent predictive factors of cirrhosis. The results were validated using 97 patients operated on from 2011 to 2015 at the same institution. Nomogram was then formulated using a multivariate Cox proportional hazards model to analyze.Results: The scoring system was ultimately composed of 4 independent predictive factors and was divided into 3 levels. The new cirrhosis system score strongly correlated with Child–Pugh score (r=0.8058, P< 0.0001) 3 months after surgery; higher cirrhosis system scores predicted poorer liver function and stronger liver damage 3 months after surgery. Then, a four-factor nomogram for survival prediction was established. The concordance indices were 0.79 for the survival-prediction nomogram. The calibration curves showed good agreement between predictions by the nomogram and actual survival outcomes.Conclusion: This new scoring system of cirrhosis can help us predict the liver function and liver injury 3 months after surgery, and the nomogram enabled accurate predictions of risk of overall survival in patients of HCC with cirrhosis after hepatectomy.Keywords: cirrhosis, hepatocellular carcinoma, HCC, pathology, scoring system, nomogram

Meng-Dan Zhao,1 Jun-Qin Li,2 Feng-Ying Chen,1 Wei Dong,3 Li-Juan Wen,4 Wei-Dong Fei,1 Xiao Zhang,1 Pei-Lei Yang,1 Xin-Mei Zhang,2 Cai-Hong Zheng1 1Department of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 2Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 3Department of Neurology, The Affiliated Yangming Hospital of Ningbo University, Yuyao People’s Hospital of Zhejiang Province, Yuyao 315400, Zhejiang, People’s Republic of China; 4Institute of Pharmaceutics, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, People’s Republic of ChinaCorrespondence: Xin-Mei Zhang; Cai-Hong Zheng Email zhangxinm@zju.edu.cn; chzheng@zju.edu.cnBackground: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a “core-shell” polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed.Methods: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined.Results: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic.Conclusion: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.Keywords: co-delivery, curcumin, reverse resistance, paclitaxel, ovarian cancer, adverse reactions

Jun Ye,1–3 Yanfang Yang,1,2 Wujun Dong,1,2 Yue Gao,1,2 Yingying Meng,1,2 Hongliang Wang,1,2 Lin Li,1,2 Jing Jin,1 Ming Ji,1 Xuejun Xia,1,2 Xiaoguang Chen,1 Yiqun Jin,3 Yuling Liu1,21State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China; 3Research and Development Department, Beijing Wehand-bio Pharmaceutical Co. Ltd, Beijing, 102600, People’s Republic of ChinaBackground: Tumor-associated macrophages (TAMs) are critical in tumor progression and metastasis. Selective targeting of TAMs holds great potential to ameliorate the immunosuppressive tumor microenvironment and enhance the efficacy of antitumor therapy. Various liposomes have been developed to target TAMs via cell-specific surface receptors either to deplete or re-educate TAMs. Since immuno-stimulation often initiates with the interaction of nanocarriers with the innate immunity cells such as macrophages, the intrinsic impact of drug-free liposomes on macrophage activation and polarization via cell interaction is one of the most critical issues in nanomedicine for promoting effective immunotherapy.Methods: In this study, conventional bare liposomes, PEGylated liposomes, and mannosylated liposomes were developed and the cytotoxicity, cellular internalization, immunostimulatory activity, targeting efficiency, antitumor efficacy, and mechanism were evaluated in vitro and in vivo.Results: All liposomes displayed an ideal particle size, good biocompatibility, and controlled release behavior. Mannosylated liposomes exhibited superior in vitro cellular internalization and tumor spheroid penetration with the aid of the mannose receptor-mediated TAMs-targeting effects. In particular, mannosylated liposomes promoted the polarization of both M0 and M2 to the M1 phenotype by enhancing the expression ratio of CD86/CD206 in vitro. Of note, mannosylated liposomes could inhibit G422 glioma tumor growth, which may be attributed to the polarization of TAMs, as evidenced by the reduction in expression level of the TAMs surface marker.Conclusion: These results indicate the potential value of mannosylated liposomes in the design of a rational delivery system to enhance the antitumor immune efficacy of immunomodulators by inducing a shift from the M2 to the M1 phenotype.Keywords: liposomes, cancer immunotherapy, tumor-associated macrophages, mannose receptor, drug delivery

Shan Tian,1,* Ruixue Li,2,* Yingyun Guo,1 Xuemei Jia,1 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Macheng City, Macheng, Hubei, People’s Republic of China *These authors contributed equally to this work Objective: Variceal hemorrhage is the primary driver of mortality in patients with portal hypertension. Recent guidelines recommended that patients with esophageal varices should receive endoscopic band ligation (EBL) or carvedilol as prophylaxis of variceal bleeding. Several clinical trials have compared carvedilol use with EBL intervention, yielding controversial results. The present study aimed to perform a meta-analysis of randomized controlled trials (RCTs) evaluating the benefits and harms of carvedilol vs EBL for the prevention of variceal bleeding.Methods: Studies were searched on Pubmed, Embase, Medline, and Cochrane library databases up to August 2018. Main outcomes in selected studies (variceal bleeding, all-cause deaths, bleeding-related deaths, and adverse events) were pooled into a meta-analysis.Results: Seven RCTs were identified in this meta-analysis, including a total of 703 patients. A total of 359 patients were randomized to carvedilol group and 354 were randomized to EBL group. No significant difference in variceal bleeding was observed between carvedilol use and EBL groups (relative ratio [RR] =0.86, 95% CI =0.60–1.23, I2=11%), without publication bias. No significant difference was found neither for all-cause deaths (RR =0.82, 95% CI =0.44–1.53, I2=66%) nor for bleeding-related deaths (RR =0.85, 95% CI =0.39–1.87, I2=42%) in four included studies. Moreover, no reduced trend was observed toward adverse events in carvedilol group compared with that in EBL group (RR =1.32, 95% CI =0.75–2.31, I2=81%).Conclusion: There is no significant difference between carvedilol use and EBL intervention for the prophylaxis of variceal bleeding in patient with esophageal varices. Large-scale clinical trials are further needed to make a confirmed conclusion. Keywords: carvedilol, endoscopic band ligation, variceal bleeding, portal hypertension

Weigang Dong, Yan Du, Shuping Ma Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China Background: The aim of the study was to investigate if first-line chemotherapy improves total survival time in non-small-cell lung cancer (NSCLC) patients complicated with severe to very severe COPD.Materials and methods: This retrospective observational clinical study included 267 consecutive NSCLC patients with COPD complications at the Department of Respiratory and Critical Care Medicine of Tianjin Chest Hospital between January 2009 and January 2018. Sixty-nine evaluable patients were included. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients receiving and those not receiving chemotherapy.Results: Forty-five and 24 patients received first-line chemotherapy plus supportive care and supportive care alone, respectively. Kaplan–Meier curves showed that patients receiving chemotherapy had a statistically significant 6-month longer median overall survival (OS) than that of patients receiving supportive care alone (14.0, 95% CI: 8.5–19.5 vs 8.0, 95% CI: 6.4–9.6, respectively) (chi2=8.857, P=0.003). In the multivariate Cox proportional hazard model adjusted for the most relevant variables, the adjusted hazard ratio (HRadj) differed significantly for the receipt of chemotherapy (HRadj=0.4464, 95% CI: 0.2495–0.7988; P=0.0066) but not for gender (HRadj=0.8527, 95% CI: 0.4461–1.6298; P=0.6297), age (HRadj=1.0021, 95% CI: 0.9609–1.0451; P=0.9214), histology (HRadj=1.4422, 95% CI: 0.6959–2.9889; P=0.3247), cancer stage (HRadj=1.9098, 95% CI: 0.8607–4.2375; P=0.1116), performance status score (HRadj=1.5155, 95% CI: 0.7523–3.0529; P=0.2446), lung function (HRadj=1.3856, 95% CI: 0.7149–2.6857; P=0.3341), or respiratory symptoms (HRadj=1.0518, 95% CI: 0.6032–1.8342; P=0.8586). Patients with grade 3/4 adverse reactions accounted for 29% (13/45) of the chemotherapy group.Conclusion: The results indicated that chemotherapy may improve the OS of NSCLC patients with severe to very severe COPD. Keywords: survival, toxicity, first-line chemotherapy, GOLD grade

Zhihong Wang, Liang He, Wei Sun, Yuan Qin, Wenwu Dong, Ting Zhang, Ping Zhang, Hao Zhang Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang 110001, China Background: The incidence of papillary thyroid cancer (PTC) is increasing faster than any other solid tumors worldwide. Invasion and metastasis are the main reasons for the poor prognosis of patients with PTC. Previously, we observed significantly low expression of miRNA-299-5p in invasive PTC tissue samples. Aim: The present study aimed to determine whether miR-299-5p plays a key role in PTC migration and invasion. Materials and methods: The miR-299-5p expression level was measured using quantitative real-time PCR in 109 human PTC samples and paired adjacent normal tissues and in the human BCPAP PTC cell line. The effects of miR-299-5p on PTC cell migration and invasion were assessed using wound healing and transwell assays. In addition, we searched for the miR-299-5p target, and the potential mechanism was demonstrated using a reporter assay and rescue experiment. Results: The expression of miR-299-5p was associated with gender and extrathyroidal extension, and an elevated level of miR-299-5p suppressed BCPAP cell migration and invasion. Estrogen receptor α (ERα) is a direct target of miR-299-5p. The expression level of ERα was significantly higher in PTC tissues and was associated with migration and invasion in PTC cells. Overexpression of ERα could impair miR-299-5p-induced inhibition of migration and invasion. As a key factor of the pathway related to PTC invasion, Gli1 can be combined with ERα and can be regulated by miR-299-5p. Conclusion: Our data suggested that miR-299-5p could participate in PTC migration and invasion and could be a potential therapeutic target for patients with aggressive PTC tumors. Keywords: miR-299-5p, papillary thyroid cancer, PTC, estrogen receptor α, ERα, migration, invasion

Wei Wang,1,* Shuang Dou,1,* Wenyan Dong,2 Mengshuang Xie,1 Liwei Cui,1 Chunyan Zheng,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Geriatric Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain. Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.Methods: In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery. All participants underwent pulmonary function test (PFT). The diagnosis of COPD was based on GOLD criteria. Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT. The HRs were estimated by Cox regression analysis.Results: Among 2,222 lung cancer patients, 32.6% coexisted with COPD. After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05–1.57). With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08–1.39). But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37–0.56; HR 0.96, 95% CI 0.94–0.99). Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49–4.30). No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.Conclusion: These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. Keywords: lung cancer, COPD, prognosis, histology, disease heterogeneity

Meng-meng Lu,1,2 Jing Bai,3 Dan Shao,4,5 Jing Qiu,1,2 Ming Li,1,2 Xiao Zheng,5 Yun Xiao,6 Zheng Wang,4 Zhi-min Chang,4 Li Chen,5 Wen-fei Dong,4 Chun-bo Tang1,2 1Department of Oral Implantology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China; 2Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; 3School of Materials Science and Engineering, Southeast University, Jiangsu Key Laboratory for Advanced Metallic Materials, Jiangning, Nanjing 211189, Jiangsu, China; 4CAS Key Laboratory of Bio Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; 5Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China; 6National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China Background: Although various organic tissue adhesives designed to facilitate would healing are gaining popularity in diverse clinical applications, they present significant inherent limitations, such as rejection, infections, toxicity and/or excessive swelling. It is highly desirable to develop efficient, biocompatible and anti-bacterial tissue adhesives for skin wound healing. Purpose: Inspired by the fact that inorganic nanoparticles can directly glue tissues through the “nanobridging effect”, herein disulfide bond-bridged nanosilver-decorated mesoporous silica nanoparticles (Ag-MSNs) was constructed as an effective and safe tissue adhesive with antibacterial and degradable properties for wound closure and healing. Materials and methods: Ag-MSNs was fabricated by controlled reduce of ultrasmall nanosilvers onto the both surface and large pore of biodegradable MSNs. The obtained MSNs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and measurement of size distribution, zeta potential, and mesopore properties. Furthermore, adhesion strength test, anti-bacterial assessment, mouse skin wound model, and MTT assays were used to investigate the tissue adhesive property, anti-bacterial effect, biodegradability and biocompatibility of the Ag-MSNs. Results: Ag-MSNs exhibited not only strong adhesive properties but also excellent antibacterial activities than that of MSNs. Importantly, this antibacterial nano-adhesive achieved rapid and efficient closure and healing of wounds in comparison to sutures or MSNs in a mouse skin wound model. Furthermore, Ag-MSNs with fast degradable behavior caused little cellular toxicity and even less systemic toxicity during wound healing. Conclusion: Our findings suggest that biodegradable Ag-MSNs can be employed as the next generation of nano-adhesives for rapid wound closure and aesthetic wound healing. Keywords: nanosilver-decorated mesoporous silica nanoparticles, nano-adhesive, wound healing, antibacterial, biodegradable

Zhenhong Fu,1,* Xia Yang,1,* Mingzhi Shen,2,* Hao Xue,1,* Geng Qian,1 Feng Cao,1 Jun Guo,1 Wei Dong,1 Yundai Chen1 1Department of Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, China; 2Department of Cardiology, Hainan Branch of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, China *These authors contributed equally to this work Background and aims: This study sought to evaluate the prognostic powers of combined use of cystatin C (Cys C) and homocysteine (Hcy) at predicting adverse events of patients >80 years old with acute myocardial infarction (AMI).Patients and methods: The analysis involved 753 patients >80 years old undergoing coronary angiography for chest pain in China from January 2006 to December 2012. Kaplan–Meier method was used for survival and major adverse cardiac events (MACE) rates. Multivariate Cox regression was performed to identify mortality predictors. Receiver operating characteristic curve analysis was performed to predict the cutoff values of Cys C and Hcy for all-cause mortality.Results: The duration of follow-up was 40–116 months (median, 63 months; interquartile range, 51–74 months). The long-term survival and event-free survival rates of AMI patients were significantly lower than those of unstable angina pectoris patients (P

Xiao-dan Zhu, Xiao-ping Lei, Wen-bin Dong Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China Abstract: Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful to relieve pulmonary function in the general population. Meanwhile, growing evidence indicates that resveratrol plays a protective role in respiratory system diseases. This review aimed to summarize the main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities. We found that resveratrol plays a protective role in the respiratory system through a variety of mechanisms, and so it may become a new drug for the treatment of respiratory system diseases. Keywords: respiratory system diseases, resveratrol, inflammation, apoptosis, oxidation

Meng-meng Lu,1 Qiu-jing Wang,2 Zhi-min Chang,3 Zheng Wang,3 Xiao Zheng,4 Dan Shao,3,4 Wen-fei Dong,3 Yan-min Zhou1 1Department of Dental Implantology, Jilin Province Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, 2Experimental Center of Functional Sciences, College of Basic Medical Sciences, Jilin University, Changchun, 3Chinese Academy of Sciences Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 4Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, People’s Republic of China Abstract: Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections. Keywords: mesoporous silica nanoparticles, silver nanoparticles, chlorhexidine, pH-responsive release, synergistic bactericidal activity, good biocompatibility

Toxigenic Vibrio cholerae strains arise upon infection and integration of the lysogenic cholera toxin phage, the CTX phage, into bacterial chromosomes. The V. cholerae serogroup O1 strains identified to date can be broadly categorized into three main groups: the classical biotype strains, which harbor CTX-cla; the prototype El Tor strains (Wave 1 strains), which harbor CTX-1; and the atypical El Tor strains, which harbor CTX-2 (Wave 2 strains) or CTX-3~6 (Wave 3 strains). The efficiencies of replication and transmission of CTX phages are similar, suggesting the possibility of existence of more diverse bacterial strains harboring various CTX phages and their arrays in nature. In this study, a set of V. cholerae strains was constructed by the chromosomal integration of CTX phages into strains that already harbored CTX phages or those that did not harbor any CTX phage or RS1 element. Strains containing repeats of the same kind of CTX phage, strains containing the same kind of CTX phage in each chromosome, strains containing alternative CTX phages in one chromosome, or containing different CTX phages in each chromosome have been constructed. Thus, strains with any CTX array can be designed and constructed. Moreover, the strains described in this study contained the toxT-139F allele, which enhances the expression of TcpA and cholera toxin. These characteristics are considered to be important for cholera vaccine development. Once their capacity to provoke immunity in human against V. cholerae infection is evaluated, some of the generated strains could be developed further to yield cholera vaccine strains.

Zhenhong Fu,1,* Geng Qian,1,* Hao Xue,1,* Jun Guo,1 Lian Chen,1 Xia Yang,1 Mingzhi Shen,2 Wei Dong,1 Yundai Chen11Department of Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Hainai Branch of Chinese People’s Liberation Army General Hospital, Sanya, Hainan, People’s Republic of China*These authors contributed equally to this workObjective: To evaluate the prognostic value of homocysteine (Hcy) in Chinese acute coronary syndrome (ACS) octogenarians.Methods: The study cohort comprised 660 consecutive ACS octogenarians who underwent coronary angiography. We classified the patients into three groups according to Hcy tertiles. Kaplan–Meier method was performed for survival and major adverse cardiac events (MACE) rates. Multivariate Cox regression was performed to identify mortality predictors. Receiver operating characteristic curve analysis was performed to predict the cutoff value of Hcy for all-cause mortality.Results: The follow-up period was 28 (inter-quartile range: 16–38) months. Diastolic blood pressure, ratios of male, renal failure and old myocardial infarction in high plasma level Hcy (H-Hcy) group were higher than those in low (L-Hcy) and middle (M-Hcy) plasma level of Hcy groups (P

Yu Pan,1,2,* Wenpeng Cai,1,* Qi Cheng,3,* Wei Dong,1 Ting An,4 Jin Yan1 1Department of Psychology and Mental Health, Second Military Medical University, Shanghai, 2Department of Psychology, Peoples Liberation Army General Hospital, Beijing, 3Department of Child and Adolescent Behavioral Medicine, The 102 Hospital of PLA, Changzhou, 4Department of Internal Medicine, The PLA Second Artillery Force General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Epidemiological studies have repeatedly investigated the association between anxiety and hypertension. However, the results have been inconsistent. This study aimed to summarize the current evidence from cross-sectional and prospective studies that evaluated this association. Methods: Seven common databases were searched for articles published up to November 2014. Cross-sectional and prospective studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratios or hazard ratios, and 95% confidence intervals (CIs) were extracted or calculated by the authors. The pooled odds ratio was calculated separately for cross-sectional and prospective studies using random-effects models. The Q test and I2 statistic was used to assess heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Results: The search yielded 13 cross-sectional studies (n=151,389), and the final pooled odds ratio was 1.18 (95% CI 1.02–1.37; PQ