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Haoxiang Wen,1,2,* Ruiming Liang,3,* Xiaofei Liu,4 Yang Yu,1 Shuirong Lin,1 Zimin Song,1 Yihao Huang,1 Xi Yu,1 Shuling Chen,5 Lili Chen,6 Baifeng Qian,1 Jingxian Shen,7 Han Xiao,8 Shunli Shen1 1Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-senUniversity, Guangzhou, Guangdong Province, People’s Republic of China; 5Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 7Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 8Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunli Shen, Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhong-Shan Road2, Guangzhou, Guangdong Province, People’s Republic of China, Email Shenshli@mail.sysu.edu.cn Han Xiao, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road2, Guangzhou, Guang- Dong Province, People’s Republic of China, Email xiaoh69@mail.sysu.edu.cnPurpose: Predicting the pathological response after neoadjuvant conversion therapy for initially unresectable hepatocellular carcinoma (HCC) is essential for surgical decision-making and survival outcomes but remains a challenge. We aimed to develop a radiomics model to predict pathological responses.Methods: We included 203 patients with HCC who underwent hepatectomy after neoadjuvant conversion therapy between 2015 and 2023 and separated them into a training set (100 patients from Center A) and a validation set (103 patients from Center B). Pathological complete response (pCR)-related radiomic features were extracted from the largest tumor layer in the arterial and portal vein phases of the CT. A synthetic minority oversampling technique (SMOTE) was used to balance the minority groups in the training set. The SMOTE radiomics model was constructed using a logistic regression model in the SMOTE training set and its performance was verified in the validation set.Results: The AUC of the preoperative modified response evaluation criteria in solid tumors (mRECIST) assessment for pCR was 0.656 and 0.589 in the training and validation sets, respectively. The SMOTE radiomics model was established based on ten radiomic features and showed good pCR-predictive performance in the SMOTE training set (AUC, 0.889; accuracy, 87.7%) and the validation set (AUC: 0.843, accuracy: 86.4%). The RFS of the radiomics-predicted-pCR group was significantly better than that of the predicted-non-pCR group in the training cohort (P = 0.001, 2-year RFS: 69.5% and 30.1% respectively) and the validation cohort (P = 0.012, 2-year RFS: 65.9% and 38.0% respectively).Conclusion: The SMOTE radiomics model has great potential for predicting pathological response and evaluating RFS in patients with unresectable HCC after neoadjuvant conversion therapy.Keywords: hepatocellular carcinoma, radiomics, pathological complete response, neoadjuvant conversion therapy

Zhaobai Lao,1,* Xuliang Fang,1,* Shuchao Shen,1,* Yuliang Zhang,2,* Xin Chen,1 Helou Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Ronghua Bao,2 Taotao Xu,3 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Changfeng Hu,4 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 4College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhudianzhuifeng@163.com Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnPurpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations.Methods: The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.Results: MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.Conclusion: Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.Keywords: systemic lupus erythematosus, intervertebral disc degeneration, nucleus pulposus, pyroptosis, NRF2/KEAP1/NF-κB pathway

Xin Qiu,1,2,* Shuang Shen,1,* Donghong Lu,2 Nizhen Jiang,3 Yifei Feng,3 Jindu Li,1 Chenglei Yang,1 Bangde Xiang1,4,5 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bangde Xiang; Chenglei Yang, Email xiangbangde@gxmu.edu.cn; chenglei2017yang@163.comBackground: Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its poor prognosis and high recurrence rates post-surgery. This study examines the predictive efficacy of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the post-hepatectomy prognosis of patients with HCC.Methods: A cohort comprising 1654 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital from 2013 to 2019 was enrolled. Patients were stratified into two groups according to the median ALI level, and then subjected to propensity score matching (PSM) in a 1:1 ratio. Kaplan-Meier survival curves, the traditional Cox proportional hazards (CPH) model, and machine learning (ML) models were employed to analyze and evaluate ALI’s prognostic significance. Furthermore, ALI’s prognostic value in digestive system tumors was validated via analysis of the National Health and Nutrition Examination Survey (NHANES) database.Results: After applying PSM, a final cohort of 1284 patients, categorized into high and low ALI groups, revealed a significantly reduced survival time in the low ALI cohort. Univariate and multivariate Cox analyses identified ALI, BCLC stage, CK19, Hepatitis B virus (HBV) DNA, lymph node metastasis, and microvascular invasion (MVI) as independent predictors of prognosis. Both traditional CPH and ML models incorporating ALI demonstrated excellent predictive accuracy, validated through calibration curves, time-dependent ROC curves, and decision curve analysis. Furthermore, the prognostic value of ALI in digestive tumors was confirmed in the NHANES database.Conclusion: The ALI exhibits potential as a prognostic predictor in patients with HCC following hepatectomy, providing valuable insights into postoperative survival.Keywords: advanced lung cancer inflammatory index, ALI, hepatocellular carcinoma, HCC, prognosis, Cox regression, machine learning, ML

Shaoqi Mou,1,* Shiyu Yan,1,* Shanhong Shen,2 Yibin Shuai,2 Gang Li,3 Zhongxia Shen,2 Ping Shen2 1Department of Psychiatry, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Sleep Medical Center, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, People’s Republic of China; 3College of Engineering, Zhejiang Normal University, Jinhua, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongxia Shen; Ping Shen, Email snowszx@sina.com; 372063474@qq.comObjective: Anxiety disorder (AD) is a common disabling disease. The prolonged disease course may lead to impaired cognitive performance, brain function, and a bad prognosis. Few studies have examined the effect of disease course on brain function by electroencephalogram (EEG).Methods: Resting-state EEG analysis was performed in 34 AD patients. The 34 patients with AD were divided into two groups according to the duration of their illness: anxious state (AS) and generalized anxiety disorder (GAD). Then, EEG features, including univariate power spectral density (PSD), fuzzy entropy (FE), and multivariable functional connectivity (FC), were extracted and compared between AS and GAD. These features were evaluated by three previously validated machine learning methods to test the accuracy of classification in AS and GAD.Results: Significant decreased PSD and FE in GAD were detected compared with AS, especially in the Alpha 2 band. In addition, FC analysis indicated that GAD patients’ connection between the left and right hemispheres decreased. Based on machine learning, AS and GAD are classified on a six-month criterion with the highest classification accuracy of up to 0.99 ± 0.0015.Conclusion: The brain function of patients is more severely impaired in AD patients with longer illness duration. Resting-state EEG demonstrated to be a promising examination in the classification in GAD and AS using machine learning methods with better classification accuracy.Keywords: electroencephalogram, EEG, disease course, anxiety disorder, brain function, machine learning

Yanqing Liu,1,* Yuqing Meng,1,* Junzhe Zhang,1 Liwei Gu,1 Shengnan Shen,1 Yongping Zhu,1 Jigang Wang1,2 1State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Department of Pharmacological Sciences, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore*These authors contributed equally to this workCorrespondence: Jigang Wang; Yongping Zhu, State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Email jgwang@icmm.ac.cn; ypzhu@icmm.ac.cnAbstract: Chloroquine is a common antimalarial drug and is listed in the World Health Organization Standard List of Essential Medicines because of its safety, low cost and ease of use. Besides its antimalarial property, chloroquine also was used in anti-inflammatory and antivirus, especially in antitumor therapy. A mount of data showed that chloroquine mainly relied on autophagy inhibition to exert its antitumor effects. However, recently, more and more researches have revealed that chloroquine acts through other mechanisms that are autophagy-independent. Nevertheless, the current reviews lacked a comprehensive summary of the antitumor mechanism and combined pharmacotherapy of chloroquine. So here we focused on the antitumor properties of chloroquine, summarized the pharmacological mechanisms of antitumor progression of chloroquine dependent or independent of autophagy inhibition. Moreover, we also discussed the side effects and possible application developments of chloroquine. This review provided a more systematic and cutting-edge knowledge involved in the anti-tumor mechanisms and combined pharmacotherapy of chloroquine in hope of carrying out more in-depth exploration of chloroquine and obtaining more clinical applications.Keywords: Chloroquine, pharmacology, applications, combined pharmacotherapy

Xingyue Gao,1 Sihao Shen,1 Wenzhong Xiang,2 Xiuzu Song2 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital, Westlake Ave 38, Hangzhou, 310002, People’s Republic of China, Email xiangwenzhong@126.comPurpose: Coronavirus disease (COVID-19) may trigger the reactivation of the latent varicella-zoster virus and may be a risk factor for herpes zoster (HZ). However, the causal relationship between COVID-19 and varicella-zoster infections remains controversial. This study aimed to estimate the causal inferences between COVID-19 and HZ.Methods: This study used a two-sample Mendelian randomization (MR) design. The inverse variance-weighted method was used as the primary method and sensitivity analyses were conducted, including the MR-Egger regression, weighted median and weighted mode. We searched at https://gwas.mrcieu.ac.uk/ using the keywords “COVID-19” for exposure data and “zoster” for outcome datasets.Results: We got 26 COVID-19 datasets and five zoster datasets. We used 26 COVID-19 datasets as exposure data corresponding to each zoster dataset for the MR analysis. There were nine datasets of COVID-19 where the number of SNPs was fewer than three in the MR analysis of the risk of HZ, varicella zoster virus (VZV) glycoprotein E and I antibody levels, anti-VZV IgG seropositivity, and post-zoster neuralgia. In addition, there were 10 datasets of COVID-19 where the number of SNPs was less than three in the MR analysis of anti-VZV IgG levels. The results of the MR analysis showed that all p-values were greater than 0.05. Sensitivity analysis revealed no evidence of horizontal pleiotropy in most two sample MR analyses.Conclusion: Our results indicate that there is no causal relationship between COVID-19 and varicella-zoster infection, HZ progression, and postherpetic neuralgia.Keywords: COVID-19, herpes zoster, varicella-zoster virus, chronic pain

Yixian Wang,1,* Xin Li,2,* Yinde Huang,3,* Qingwei Gang,1 Mingyu Liu,1 Han Zhang,1 Shikai Shen,1 Yao Qi,1 Jian Zhang1 1Department of Vascular and Thyroid Surgery, The First Hospital, China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Head and Neck Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang, Email jianzhang@cmu.edu.cnBackground: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC.Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids.Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells.Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.Keywords: immunogenic cell death, LncRNA, papillary thyroid carcinoma, prognosis

Jiaxing Zhang,1,2,* Liwei Gu,3,* Yumao Jiang,4,* Yun Ma,5,* Ziyue Zhang,3 Shengnan Shen,3 Shuo Shen,3 Qing Peng,6 Wei Xiao2,7 1Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guang Dong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 3Artemisinin Research Center and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Gannan Medical University, Ganzhou, Jiang Xi, People’s Republic of China; 5Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 6Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Peng; Wei Xiao, Email pengqing85@163.com; xw7688@smu.edu.cnBackground: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy.Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored.Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1.Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI. Keywords: artesunate, liposomes, AKI, cisplatin, oxidative stress, inflammation

Yiping Lu,1,* Nan Mei,1,* Yinwei Ying,1,* Dongdong Wang,1 Xuanxuan Li,1 Yajing Zhao,1 Yuqi Zhu,1 Shun Shen,2,3 Bo Yin1 1Department of Radiology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China; 3Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Yin; Shun Shen, Email yinbo@fudan.edu.cn; nanocarries@gmail.comAbstract: Surgical removal together with chemotherapy and radiotherapy has used to be the pillars of cancer treatment. Although these traditional methods are still considered as the first-line or standard treatments, non-operative situation, systemic toxicity or resistance severely weakened the therapeutic effect. More recently, synthetic biological nanocarriers elicited substantial interest and exhibited promising potential for combating cancer. In particular, bacteria and their derivatives are omnipotent to realize intrinsic tumor targeting and inhibit tumor growth with anti-cancer agents secreted and immune response. They are frequently employed in synergistic bacteria-mediated anticancer treatments to strengthen the effectiveness of anti-cancer treatment. In this review, we elaborate on the development, mechanism and advantage of bacterial therapy against cancer and then systematically introduce the bacteria-based nanoprobes against cancer and the recent achievements in synergistic treatment strategies and clinical trials. We also discuss the advantages as well as the limitations of these bacteria-based nanoprobes, especially the questions that hinder their application in human, exhibiting this novel anti-cancer endeavor comprehensively. Keywords: bacteria-based nanoprobe, bacteria-mediated synergistic cancer therapy, nanomedicine, tumor targeting, tumor immune microenvironment, clinical trial

Shuyun Zhang,1,* Lijuan Wu,1,* Xue Li,1 Li Yang,1 Sujuan Shen,1 Hong Shen,1 Dan Zhao,2 Lin Qi2,3 1Center of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 2Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 3State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Qi, Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China, Tel +86-13962187070, Email drhuan@126.comPurpose: Karyotype analysis of villus chromosomes in spontaneous abortion by high-throughput ligation-dependent probe amplification (HLPA) was performed to explore relationship between spontaneous abortion and chromosomal abnormalities in spontaneous abortion tissues.Patients and Methods: The karyotypes of chromosomes of villus tissues from 516 patients with spontaneous abortion who were admitted to our hospital between 2014 and 2019 were analyzed. The data were grouped by the age (ie, ≤ 29, 30– 35, and ≥ 36 years old) in which embryonic chromosomal abnormality rate, and abnormal distribution of chromosome number in abortion tissue of 294 patients.Results: The examination of 516 samples of spontaneous abortion tissues showed that the chromosomes of 294 samples were abnormal, and the abnormality rate was 60.97%. Among 294 samples with chromosomal abnormalities, 136 (89.47%) samples had numerical chromosomal abnormalities, 15 (9.87%) samples had structural chromosomal abnormalities, and 1 (0.07%) sample had uniparental disomy. A total of 308 couples voluntarily underwent peripheral blood chromosome analysis. The results showed that 56 couples had abnormality in one or both spouses, and rate of embryonic chromosomal abnormality in these 26 cases with chromosomal abnormalities was 100%.Conclusion: Numerical and structural chromosomal abnormalities are among the important causes of embryonic arrest, while the increase in age could also be a high-risk factor for embryonic chromosomal abnormality. Therefore, examination of the karyotypes of embryo chorionic villus may help understand the reasons of embryonic arrest, which could provide important guidance for more genetic counseling for patients with early spontaneous abortion, as well as improving the preconception preparation.Keywords: spontaneous abortion, villus tissue, HLPA test, chromosomal abnormality

Shenghua Shen, Yuan Xiao Department of Pulmonary and Critical Care Medicine, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, People’s Republic of ChinaCorrespondence: Yuan Xiao, Department of Pulmonary and Critical Care Medicine, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, 29 Xinglong Lane, Tianning District, Changzhou, Jiangsu, 213004, People’s Republic of China, Tel +86 13775118679 ; +86 519-88125317, Email yuanyuanxiao12@outlook.comPurpose: This study was to evaluate the association between C-reactive protein (CRP) to albumin (ALB) ratio (CAR) and the risk of mortality in patients with chronic obstructive pulmonary disease (COPD).Methods: In this retrospective cohort study, clinical data were extracted from the National Institutes of Health National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2010. Cox proportional hazard regressions were performed to assess the association between CAR and 5-year mortality in COPD patients. Subgroup analyses were applied to identify the consistency of the association based on the severity of COPD, gender, body mass index (BMI), smoking status, cardiovascular disease (CVD), and chronic kidney disease (CKD), and diabetes. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive performance of CAR.Results: A total of 1210 COPD patients were included, of which 110 COPD patients (9.09%) had 5-year mortality. The mean follow-up was 57.76 (0.33) months. A higher CAR was associated with an increased risk of 5-year mortality in COPD patients [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.07 to 3.50, P =0.029)]. Subgroup analysis showed that the association between CAR and mortality was especially suitable for COPD patients with mild COPD, in COPD patients who were still smoking, in COPD patients with BMI

Sihao Shen,1 Jiangfeng Feng,1 Xiuzu Song,2 Wenzhong Xiang2 1Department of Dermatology, Hangzhou Third People’s Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital; Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Westlake Ave 38, Hangzhou, 310009, People’s Republic of China, Tel +86 13588004268, Email xiangwenzhong@126.comAbstract: Periorificial dermatitis (PD) is an inflammatory disorder of the facial skin that mainly occurs around the mouth and manifests as erythema, papules, pustules, scales and other lesions. Special attention is needed in the clinical diagnosis of PD to distinguish it from acne, seborrheic dermatitis (SD), granulomatous rosacea (GR), sarcoidosis and childhood granulomatous periorificial dermatitis (CGPD). We used reflectance confocal microscopy (RCM) images of a patient with PD to assist in the diagnosis of PD. RCM of PD showed slight oedema of the spinous layer. Numerous dendritic cells, scattered hair follicular keratotic plugging and hair follicle dilatation were observed. The dilation and congestion of superficial dermis blood vessels, an increasing vascular density and accelerated blood flow, and a greater abundance of infiltrated inflammatory cells were also detected.Keywords: periorificial dermatitis, reflectance confocal microscopy, acne, seborrheic dermatitis, granulomatous rosacea, sarcoidosis, childhood granulomatous periorificial dermatitis

Huan Wang,1 Cody Abbey,1 Thomas Kennedy,1 Erik Feng,1 Robin Li,1 Finley Liu,1 Annli Zhu,1 Sharon Shen,1 Prateek Wadhavkar,1 Scott Rozelle,1 Manpreet K Singh2 1Stanford Center on China’s Economy and Institutions, Stanford University, Stanford, CA, USA; 2Stanford School of Medicine, Stanford University, Stanford, CA, USACorrespondence: Cody Abbey, Stanford Center on China’s Economy and Institutions, Stanford University, Stanford, CA, USA, Tel +1 650-723-4581, Email cjabbey@stanford.eduPurpose: We examine how adolescent free time allocation—namely, screen time and outdoor time—is associated with mental health and academic performance in rural China.Methods: This paper used a large random sample of rural junior high school students in Ningxia (n = 20,375; age=13.22), with data collected from self-reported demographic questionnaires (to assess free time allocation), the Strengths and Difficulties Questionnaire (to assess mental health), and a standardized math test (to measure academic performance). We utilized a multivariate OLS regression model to examine associations between free time allocation and adolescent outcomes, controlling for individual and family characteristics.Results: Our sample’s screen time and outdoor time both averaged around 1 hour. About 10% of the sample adolescents reported behavioral difficulties, while a similar percentage (11%) reported abnormal prosocial behaviors. Adolescents with higher levels of screen time (> 2 hours) were 3 percentage points more likely to have higher levels of behavioral difficulties (p< 0.001), indicating that excessive screen time was associated with worse mental health. Meanwhile, outdoor time was associated with better mental health, and positive correlations were observed at all levels of outdoor time (compared to no outdoor time, decreasing the likelihood of higher levels of behavioral difficulties by between 3 and 4 percentage points and of lower prosocial scores by between 6 and 8 percentage points; all p’s< 0.001). For academic performance, average daily screen times of up to 1 hour and 1– 2 hours were both positively associated with standardized math scores (0.08 SD, p< 0.001; 0.07 SD, p< 0.01, respectively), whereas there were no significant associations between outdoor time and academic performance.Conclusion: Using a large sample size, this study was the first to examine the association between adolescent free time allocation with mental health and academic performance, providing initial insights into how rural Chinese adolescents can optimize their free time.Keywords: adolescent outcome, free time allocation, correlational analysis, developing countries

Jihong Gu,1,&ast; Shucheng Shen,1,&ast; Mengyuan Xiong,1,2 Jin Zhao,1,2 Hongpan Tian,1 Xiao Xiao,1,3 Yirong Li1– 3 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Wuhan Research Center for Infectious Diseases and Tumors of the Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China; 3Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yirong Li, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430061, People’s Republic of China, Tel +8618602718052, Email liyirong838@163.comBackground: Staphylococcus aureus (S. aureus) was able to rapidly evolve and adapt under the pressure of antibiotics, host immune and environmental change. After Corona Virus Disease 2019 (COVID-19) epidemic in Wuhan, China, a large number of disinfectants were used, which might result in rapid evolution of S. aureus.Methods: A total of 619 S. aureus isolates were collected from Zhongnan Hospital, Wuhan University from 2018 to 2021, including group BEFORE (309 strains collected before COVID-19 pandemic) and group AFTER (310 strains collected after COVID-19 pandemic), for comparing the changes of molecular epidemiology. The molecular characteristics of isolates were analyzed by Multi-locus sequence typing (MLST), spa, chromosomal cassette mec (SCCmec) typing, virulence genes were screened by the PCR, antibiotic susceptibility test was carried out by the VITEK system.Results: Thirty-six sequence types (STs) belonging to 14 clone complexes (CCs) were identified. ST5 was the most prevalent clone in both groups, and ST7, ranking the sixth in group BEFORE, became the second dominant clone in group AFTER (6.5% vs 10.0%), whereas ST239 decreased from the seventh to the fourteenth (5.8% vs 1.9%). ST7 in group AFTER had a higher positive rate of virulence genes, including hlb, fnbB, seb, lukDE, sdrE and the proportion of ST7-t091 MRSA strains increased from 19.1% to 50% compared with group BEFORE. Though no significant difference of MRSA proportion was found between two groups, SCCmec type-III in group AFTER decreased (p< 0.01). Though the rate of multidrug-resistance (MDR) decreased, the virulence genes hlb, hlg, fnbB, seb and pvl carrying rates were significantly elevated in MRSA strains of group AFTER.Conclusion: After COVID-19 pandemic, ST7 becomes one of the predominant S. aureus clones in Wuhan and the carrying rate of SCCmec and virulence genes is on the rise. Therefore, it is essential to strengthen the surveillance of ST7 S. aureus clone.Keywords: Staphylococcus aureus, molecular characterization, antimicrobial resistance, virulence gene, disinfectant

Lanyao Yang1,2 &ast;, Lanlan Wu3 &ast;, Yao Liu,3 Hengying Chen,4 Yuanhuan Wei,3 Ruifang Sun,3 Siwen Shen,3 Bowen Zhan,1,2 Jianjun Yang,1,2 Guifang Deng3 1Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Deng, Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, No. 89 Taoyuan Road, Shenzhen, Guangdong, 518052, People’s Republic of China, Email misyfly@163.com Jianjun Yang, Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, No. 1160 Shengli Road, Yinchuan, Ningxia, 750004, People’s Republic of China, Email yangjj@nxmu.edu.cnObjective: This study evaluated the associations of serum ferritin (SF) concentration during pregnancy with the risk of adverse maternal and fetal pregnancy outcomes.Methods: We conducted a retrospective study of 2327 pregnant women from 2015 to 2020 in Guangdong, China. SF concentrations were measured at 16– 18th and 28– 32th week of gestation. Logistic regression models were applied to estimate the association between SF concentration and the risk of adverse pregnancy outcomes.Results: After multivariable adjustment, the odds ratio (OR) of the highest quartile of SF concentration at 16– 18th week of gestation was 1.43 (95% confidence interval [CI]: 1.09, 1.89) for gestational diabetes mellitus (GDM) and 1.79 (95% CI: 1.15, 2.79) for small for gestational age (SGA) when compared with the lowest quartile. At 28– 32th week of gestation compared with the lowest quartile, women with SF in the highest quartile had an increased risk of SGA (OR: 1.62; 95% CI: 1.01, 2.62). Moreover, the lowest quartile of SF concentration decreased risk of SGA by 90% (95% CI: 0.01, 0.80) when compared with the highest quartile among pregnancy women with GDM.Conclusion: Elevated SF concentrations increased the risk of GDM and SGA during pregnancy. Maintaining an appropriately low level of maternal SF at 28– 32th week of gestation in women with GDM could reduce the risk of SGA.Keywords: ferritin, adverse pregnancy outcomes, gestational diabetes mellitus, small for gestational age

Jin Cao,&ast; Mingxue Zheng,&ast; Zhenyan Sun, Zhiye Li, Xueyong Qi, Song Shen School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Song Shen; Xueyong Qi, School of Pharmacy, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People’s Republic of China, Tel +86-0511-88795939, Email jsda.shensong@163.com; qixyemail@163.comBackground: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.Results: When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.Keywords: sonodynamic therapy, flash nanoprecipitation, manganese dioxide, PLGA nanoparticle, GSH-depletion, hypoxia

Danmei Lv, Shanshan Shen, Xujiao Chen Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310013, People’s Republic of ChinaCorrespondence: Xujiao Chen, Department of Geriatrics, Zhejiang Hospital, Lingyin Road #12, Hangzhou, 310013, People’s Republic of China, Email lily197459@163.comBackground: In recent years, dynapenic abdominal obesity has received more and more attention. This article aimed to explore the relationship between dynapenic abdominal obesity and fall risk in older adults.Methods: In this cross-sectional study, according to waist circumference (≥ 90 cm for men and ≥ 85 cm for women) and handgrip strength (< 28 kg for men and < 18 kg for women), 551 older adults were divided into four groups: dynapenic abdominal obese (D/AO), dynapenic nonabdominal obese (D/NAO), nondynapenic abdominal obese (ND/AO) and nondynapenic nonabdominal obese (ND/NAO). Fall risk was measured by the Tinetti performance-oriented mobility assessment (POMA). Binary logistic regression was used to explore the relationship between D/AO and fall risk.Results: D/AO was related to POMA score (odds ratio [OR]=3.39; 95% confidence interval [CI]: 1.47– 7.81; P=0.004) after adjusting the confounding variables. However, D/NAO (OR=1.51; 95% CI:0.69– 3.32; P=0.302) and ND/AO (OR=1.48; 95% CI:0.74– 2.99; P=0.272) were not associated with POMA score.Conclusion: This study suggests that older adults with D/AO have a higher risk of falls. Therefore, it is necessary to strengthen the attention to D/AO and relevant interventions should be implemented.Keywords: dynapenic abdominal obesity, fall risk, older adult

Yiwen Qiu, Shu Shen, Yi Yang, Wentao Wang Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wentao Wang, Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610041, People’s Republic of China, Tel +86 18980601895, Fax +86-028-85422871, Email wwtdoctor02@163.comIntroduction: Alveolar echinococcosis is a lethal zoonosis caused by Echinococcus multilocularis (E.m) larvae. The mechanism by which E.m evades host immune attacks and ensures long-term survival remains unexplained. The complement system is a cascade of sequentially activated complement proteins that results in opsonization-related phagocytosis or membrane lysis of invading organisms. Excretory/secretory proteins (ESPs) of parasites are the main antigens that induce the immune response and play important roles in the long-term survival.Methods: We investigated the possibility that E.m inhibits complement activation through ESPs and examined the potential related mechanism. A haemolysis assay was used to determine if and how in vitro culture medium of E.m containing ESPs can inhibit complement activation. Potential ESPs were annotated using bioinformatics methods, and one ESP was subsequently expressed as a recombinant protein with a eukaryotic expression system. The ability of this protein to inhibit complement activation was also tested by haemolysis assay.Results: These assays showed that in vitro culture medium of E.m inhibited activation of the complement classical pathway. EmuJ_000439500 encodes a protein containing seven Sushi domains, which was the only potential E.m-derived complement inhibitor (Em-CI, UniProt: A0A068Y4F2) annotated among the 653 ESPs. Recombinant Em-CI also displayed the ability to inhibit activation of the complement classical pathway.Discussion: The discovery of Em-CI sheds light on the mechanism by which E.m escapes killing by the complement system and provides potential targets for immunotherapy for parasitic diseases.Keywords: Echinococcus multilocularis, alveolar echinococcosis, complement inhibition, excretory/secretory protein

Shen Shen,1,2 Yanfang Wang3 1Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Shen ShenGene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, 450052, Henan, People’s Republic of ChinaEmail fccshenk@zzu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is a common clinical malignancy. Recent studies reported that E2F transcription factor 2 (E2F2) plays a significant role in tumor progression. However, its expression and biological function in HCC are still unclear. Therefore, we explored the relationship between E2F2 expression and tumor progression in HCC.Methods: In this study, we utilized some online tools to explore the E2F2 expression in pan-carcinoma and HCC. The association of E2F2 expression with the clinical characteristics and prognosis of HCC was further studied. In addition, we explored the co-expressed genes of E2F2 and mined the positively/negatively corrected significant genes and excavated the possible functions. Meanwhile, the hub gene set was constructed based on protein–protein interaction (PPI) network, and the relationship between E2F2 and immunity was discovered.Results: We observed that the expression level of E2F2 was generally upregulated in HCC. However, E2F2 expression was not significantly different between HCC and normal tissues in regard to the disease stage 4. Furthermore, we also observed the poor prognosis in patients with high E2F2 expression. The co-expressed genes of E2F2 were identified and further detected. Thereafter, we identified the positively/negatively corrected significant genes and constructed the hub gene network of E2F2 based on PPI network. We also found that E2F2 expression was positively correlated with the infiltration levels of CD4+ T, CD8+ T cells, macrophages, neutrophils, and dendritic cells.Conclusion: Our findings suggested that E2F2 could be a potential prognostic factor for HCC, which could provide a therapeutic target for the molecular treatment of HCC.Keywords: E2F2, hepatocellular carcinoma, prognosis, hub genes, diagnosis

Ting Sun,1 Tao Wang,1 Yiwen Qiu,1 Shu Shen,1 Xianwei Yang,1 Yi Yang,1 Bin Huang,2 Wentao Wang1 1Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wentao Wang Email wwtdoctor02@163.comBackground: Sarcopenia and visceral adiposity have been shown to be associated with postoperative complications in numerous diseases. However, their effects on the postoperative complications of end-stage hepatic alveolar echinococcosis (HAE) patients undergoing ex vivo liver resection and autotransplantation (ELRA) remain unclear.Methods: This retrospective study included 101 end-stage HAE patients who underwent ELRA from January 2014 to August 2020. We measured the skeletal muscle and adipose tissue of all patients at the level of the third lumbar vertebra on plain abdominal computed tomography (CT) images and subsequently derived an equation via least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the sarcopenia score. Univariate and multivariate regression were performed to reveal the relationship between major postoperative complications and perioperative clinical data, and the obtained nomogram was validated with the bootstrapping method.Results: The sarcopenia score was constructed as a personalized indicator to evaluate sarcopenia and visceral adiposity in each patient. Logistic regression analysis finally selected duration from primary diagnosis to obvious symptoms (OR=1.024, 95% CI, 1.007– 1.042), surgical time (OR=1.003, 95% CI, 0.999– 1.007) and sarcopenia score (OR=4.283, 95% CI, 1.739– 10.551) as independent risk factors for predicting major postoperative complications following ELRA for end-stage HAE patients. The area under the receiver operating characteristic curve (AUROC) of 0.807 (95% CI, 0.720– 0.895) and the calibration curve for this prediction model were satisfactory.Conclusion: The sarcopenia score, which systematically evaluates the skeletal muscle and adipose tissue of end-stage HAE patients, was a significant predictive factor for major postoperative complications of ELRA. Relevant interventions should be conducted for those who have a high risk of postoperative complications according to the nomogram.Keywords: hepatic alveolar echinococcosis, liver transplantation, hepatectomy, sarcopenia, postoperative complications

Yixuan Zhang,1,&ast; Haochen Su,2,&ast; Haibo Wang,3,&ast; Chenghu Xu,1 Siqi Zhou,4 Jing Zhao,1 Shanshan Shen,1 Guifang Xu,1 Lei Wang,1 Xiaoping Zou,1 Shu Zhang,1 Ying Lv1 1Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Cyttelbio Corporation, Beijing, People’s Republic of China; 4Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated of Jiangsu University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu Zhang; Ying Lv Email zhangsgastro@nju.edu.cn; lvying@njglyy.comBackground: Circulating tumor cells (CTCs) were a promising liquid biopsy for pancreatic cancer (PC) but circulate in low counts in peripheral blood. We evaluated the diagnostic and prognostic values of portal vein (PoV) CTCs in PC patients.Methods: PoV was aspirated under EUS guidance from 40 patients with suspected pancreaticobiliary cancers. Epithelial–mesenchymal-transition-related subtypes of CTCs were identified via immunofluorescence using EpCAM and Twist antibodies. The diagnostic and prognostic performance of PoV CTCs was investigated by receiver-operating characteristic (AUC) curve and Kaplan–Meier survival analysis.Results: In total, 40 patients including 31 with PC, 4 with non-pancreatic periampullary cancer and 5 with benign pancreatic diseases (BPD) were enrolled. CTCs were detected more in PoV compared with peripheral blood. PoV CTC numbers in BPD patients were lower than in PC patients. The number of PoV CTCs, especially mesenchymal-CTCs (M-CTCs), was positively correlated with the tumor burden, instead of epithelial-CTCs (E-CTCs). The combination of PoV CTC numbers and CA19-9 demonstrated better diagnostic efficiency (AUC value 0.987) than either alone in differentiating PC with BPD. Moreover, the diagnostic efficacy of PoV CTCs and M-CTCs were obviously better than that of E-CTCs and CA19-9 in distinguishing early and late stage PC. Lastly, high PoV CTC and M-CTC numbers were both associated with shorter overall survival.Conclusion: Acquisition of the PoV samples in PC patients via EUS-guided procedures has been proved safe and feasible. PoV CTCs, especially M-CTCs, have great potentials in diagnosing and predicting the prognosis of PC, especially in combination with CA19-9.Keywords: circulating tumor cell, endoscopic ultrasound, portal vein blood, diagnosis, prognosis

Yiwen Qiu, Tao Wang, Xianwei Yang, Shu Shen, Yi Yang, Wentao Wang Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Wentao WangDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610041, People’s Republic of ChinaTel +86 18980601895Fax +86 28-85422871Email wwtdoctor02@163.comBackground: Spontaneous rupture bleeding is a fatal hepatocellular carcinoma (HCC) complication and a significant determinant of survival outcomes. This study aimed to develop and validate a novel artificial neural network (ANN)-based survival prediction model for patients with spontaneous HCC rupture after transcatheter arterial embolization (TAE).Methods: Patients with spontaneous HCC rupture bleeding who underwent TAE at our hospital between January 2010 and December 2018 were included in our study. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to screen clinical variables related to prognosis. We incorporated the above clinical variables identified by LASSO Cox regression into the ANNs model. Multilayer perceptron ANNs were used to develop the 1-year overall survival (OS) prediction model for patients with spontaneous HCC ruptured bleeding in the training set. The area under the receiver operating characteristic curve and decision curve analysis were used to compare the predictive capability of the ANNs model with that of existing conventional prediction models.Results: The median survival time for the whole set was 11.8 months, and the 1-year OS rate was 47.5%. LASSO Cox regression revealed that sex, extrahepatic metastasis, macroscopic vascular invasion, tumor number, hepatitis B surface antigen, hepatitis B e antigen, tumor size, alpha-fetoprotein, fibrinogen, direct bilirubin, red blood cell, and γ-glutamyltransferase were risk factors for OS. An ANNs model with 12 input nodes, seven hidden nodes, and two corresponding prognostic outcomes was constructed. In the training set and the validation set, AUCs for the ability of the ANNs model to predict the 1-year OS of patients with spontaneous HCC rupture bleeding were 0.923 (95% CI, 0.890– 0.956) and 0.930 (95% CI, 0.875– 0.985), respectively, which were higher than that of the existing conventional models (all P < 0.0001).Conclusion: The ANNs model that we established has better survival prediction performance.Keywords: hepatocellular carcinoma spontaneous rupture bleeding, HCC spontaneous rupture bleeding, least absolute shrinkage and selection operator regression, LASSO regression, artificial neural networks, ANNs, survival, prognosis

Ting Sun,1 Ruicen Li,2 Yiwen Qiu,1 Shu Shen,1 Wentao Wang1 1Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Health Management Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wentao WangDepartment of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610041, People’s Republic of ChinaTel +86 18980601895Email wwtdoctor02@163.comBackground: The thresholds of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (PIVKA-II) when detecting hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with antiviral nucleoside analog (NA) remain controversial. A relevant integrated nomogram needs to be developed.Methods: We enrolled a consecutive series of 5666 cases diagnosed with CHB either with or without antiviral agents and randomly allocated them to the training set (n=3966, 70.00%) and the validation set (n=1700, 30.00%).Results: In the training set, the levels of AFP and PIVKA-II of NA-treated patients were significantly lower than those of untreated patients. The most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL (a sensitivity of 39.77% and a specificity of 92.17%) and 35.50 mAU/mL (a sensitivity of 84.85% and a specificity of 69.43%) for NA-treated patients. As for BCLC-0/A HCC, the most appropriate cut-off values of AFP and PIVKA-II were 151.40 ng/mL and 32.50 mAU/mL for NA-treated patients, respectively. A logistic regression model composed of AFP, PIVKA-II and other clinical parameters to predict the risk of HBV-related HCC for NA-treated patients was established and verified to have an AUROC of 0.868 (95% CI, 0.827– 0.909) for all-stage HCC and an AUROC of 0.856 (95% CI, 0.809– 0.903) for BCLC-0/A HCC.Conclusion: The new detection thresholds of AFP and PIVKA-II might lead to the ability to perform early detection for hepatoma in NA-treated patients and the innovative risk prediction model is a valuable tool for identifying high-risk CHB patients.Keywords: hepatitis B virus, hepatocellular carcinoma, alpha-fetoprotein, des-gamma-carboxy prothrombin, antiviral agents, nomogram

Haizhou Qiu, Chang Liu, Min Huang, Shu Shen, Wentao Wang Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaCorrespondence: Wentao WangDepartment of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail wwtdoctor02@163.comPurpose: The prognosis of intrahepatic cholangiocarcinoma (ICC) patients after surgical resection remains poor. Effective prognostic biomarkers are expected to stratify ICC patients and optimize their treatment strategies. To investigate the prognostic value of carbohydrate antigen 19-9 (CA19-9), aspartate aminotransferase to lymphocyte ratio index (ALRI), and their combination (CAC) in predicting long-term outcomes in ICC patients after hepatectomy.Patients and Methods: ICC patients underwent initial hepatectomy for curative purpose from January 2009 to September 2017 were reviewed retrospectively. Area under the receiver operating characteristics curve (AUC) was used to distinguish the identification effectiveness of three different measures. Kaplan–Meier curves and Cox proportional hazards regression were used to assess the value of preoperative CAC grade in predicting overall survival (OS) and disease-free survival (DFS).Results: A total of 530 patients were included and randomly divided into two groups (derivation cohort and validation cohort). During a median follow-up of 18 months (1– 115.4 months), 317 patients (59.8%) died and 381 patients (71.9%) developed tumor recurrence. Lower ALRI, decreased serum CA19-9 level and CAC grade were found to be associated with better OS and DFS (both P< 0.001). Importantly, the AUC for CAC grade was significantly greater than ALRI and CA19-9. In addition, results from Cox proportional hazards regression from both cohorts suggest that tumor number, node invasion, and CAC grade as independent prognostic factors for both OS and DFS.Conclusion: This study demonstrated that CAC grade is a valuable biomarker for the prognosis of ICC patients. Specifically, patients with elevated CAC grades were correlated to worse long-term outcome after the hepatectomy. Our data suggest that increased CAC grades can be used to stratify patients and help to decide their treatment strategies.Keywords: intrahepatic cholangiocarcinoma, carbohydrate antigen 19-9, aspartate aminotransferase to lymphocyte ratio, hepatectomy, prognostic predictor, long-term outcomes

Jihui Yue,1,2,&ast; Shuming Zhong,1,&ast; Aimin Luo,3 Shunkai Lai,1 Tingting He,4 Yuchong Luo,2 Ying Wang,5 Yiliang Zhang,1 Shiyi Shen,4 Hui Huang,4 Shenglin Wen,2 Yanbin Jia1 1Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 3Department of Psychology, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, People’s Republic of China; 4School of Management, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China; 5Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanbin JiaDepartment of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of ChinaTel +86 13392489168Fax +86 020-38688888Email Yanbinjia2006@163.comPurpose: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS).Patients and Methods: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10.Results: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC.Conclusion: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.Keywords: obsessive compulsive disorder, prefrontal cortex, working memory, neurometabolites, proton magnetic resonance spectroscopy

Min Li,1,* Kun Fan,1,* Bohao Zheng,1,* David Zekria,2 Tao Suo,1 Han Liu,1 Sheng Shen,1 Houbao Liu,1 Xiaoling Ni1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK*These authors contributed equally to this workCorrespondence: Xiaoling Ni; Houbao LiuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 64041998; +86 21 64041997Email ni.xiaoling@zs-hospital.sh.cn; liu.houbao@zs-hospital.sh.cnPurpose: Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies.Materials and Methods: Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo.Results: Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC.Conclusion: SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.Keywords: gallbladder cancer, SLC39A4 (ZIP4), proliferation, migration, potential therapeutic target

Xin Zhou,1 Shou-Gen Cao,1 Xiao-Jie Tan,1 Xiao-Dong Liu,1 Ze-Qun Li,1 Ling-Xin Kong,2 Yu-Long Tian,1 Dan Liu,1 Shuai Shen,1 Yu-Qi Sun,1 Hai-Tao Jiang,1 Yan-Bing Zhou1 1Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Yan-Bing ZhouDepartment of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao City, Shandong Province, People’s Republic of ChinaTel +86-13708971773Email zhouyanbing999@aliyun.comPurpose: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy.Patients and Methods: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1– 3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms.Results: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1– 5 (average: 2.55± 0.21 vs 3.10± 0.42, P< 0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63± 16.74 vs 72.60± 20.92, P< 0.001) and defecation (72.20± 16.24 vs 95.78± 17.75, P< 0.001) were shorter; the frequency of nausea were fewer (1.88± 1.09 vs 2.58± 0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63± 0.63 vs 6.93± 0.69, P< 0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported.Conclusion: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.Keywords: stomach neoplasms, acupuncture therapy, enhanced recovery after surgery, pain management, gastrointestinal function

Tao Wang,1,* Jinfu Zhang,1,* Wanxiang Wang,2 Xianwei Yang,1 Junjie Kong,3 Shu Shen,1 Wentao Wang1 1Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Hepatobiliary, Pancreatic, and Splenic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 3Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wentao WangDepartment of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaTel +86 18980601895Fax +86-28-85422871Email wwtdoctor02@163.comBackground: There are few studies on the prognosis of elderly intrahepatic cholangiocarcinoma (iCCA) patients after liver resection. The aims of this study were to assess the cumulative incidences of cancer-specific mortality in elderly iCCA patients and to construct a corresponding competing risk nomogram for elderly iCCA patients.Methods: We performed a retrospective analysis of elderly patients with iCCA who underwent liver resection between January 2006 and December 2019. Eligible elderly iCCA patients were randomly divided into training and validation sets at a ratio of 7:3. Based on the results of multivariate analysis using the Fine-Gray competing risk model, we developed a competing risk nomogram using data from the training set to predict the cumulative probabilities of iCCA-specific mortality. The performance of the nomogram was measured by the concordance index (C-index) and calibration curves. To evaluate the clinical usefulness of the nomogram, the clinical benefit was measured by using decision curve analysis (DCA). Furthermore, the patients were categorized into two groups according to the dichotomy values of the nomogram-based scores, and their survival differences were assessed using Kaplan–Meier and cumulative incidence function (CIF) curves.Results: The 1-year, 3-year and 5-year cumulative iCCA-specific mortalities were 19.7%, 48.3% and 56.1%, respectively, for elderly iCCA patients. The multivariate Fine-Gray analysis indicated that microvascular invasion, macroscopic vascular invasion and lymph node metastasis were related to a significantly higher likelihood of iCCA specific mortality. The established nomogram was well calibrated and had a good discriminative ability, with a concordance index (C-index) of 0.742 (95% CI, 0.708– 0.748). Furthermore, the DCA indicated that the nomogram had positive net benefits compared with the conventional staging systems. In the training set and validation sets, the high-risk group had the higher probabilities of iCCA cancer-specific mortality than the low-risk group; meanwhile, the patients in the high-risk the group had significantly poorer overall survival (OS) than those in the low-risk group.Conclusion: Elderly iCCA patients had comparable long-term outcomes with non-elderly iCCA patients. In addition, we constructed a prognostic nomogram for predicting survival in elderly iCCA patients based on the competing risk analysis. The competing risk nomogram displayed excellent discrimination and calibration.Keywords: intrahepatic cholangiocarcinoma, iCCA, liver resection, elderly patients, competing risk analysis, nomogram

Ling Lu,1,* Qiaoyan Liang,2,* Shiyue Shen,3 Lei Feng,3 Longtao Jin,1 Zhao feng Liang3 1Women and Children Health Hospital of Zhenjiang, Zhenjiang, Jiangsu 212001, People’s Republic of China; 2People’s Liberation Army Navy No. 971 Hospital, Qingdao, Shandong 266000, People’s Republic of China; 3Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Longtao JinWomen and Children Health Hospital of Zhenjiang, 20 Zhengdong Road, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaEmail 13862451566@163.comZhao feng LiangJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, People’s Republic of ChinaEmail liangzhaofeng@ujs.edu.cnAbstract: Lung cancer is one of the most common causes of cancer-related deaths worldwide. Tobacco smoke is the single greatest risk factor of lung cancer. Although enormous progress in understanding the molecular mechanisms by which tobacco smoke leading to lung cancer has been made, the molecular pathogenesis remains largely unclear. Cancer stem cells have been implicated in cancer initiation, development, and drug resistance. In this review, we reviewed the relationship between tobacco smoke and lung cancer, the key role of cancer stem cells in lung cancer and other tumors. More importantly, we elucidate the mechanism of tobacco smoke promoting lung cancer from the perspective of the characteristics of cancer stem cells induced by tobacco smoke.Keywords: lung cancer, tobacco smoke, cancer stem cells, mechanism

Peng Gao,1,2 Shuo Shen,1,2 Xiaodong Li,3 Dandan Liu,1,2 Yuqing Meng,1,2 Yanqing Liu,1,2 Yongping Zhu,1,2 Junzhe Zhang,1,2 Piao Luo,1,2 Liwei Gu1,2 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 2Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3Institute of Chinese Materia Medica, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, People’s Republic of ChinaCorrespondence: Liwei Gu Email lwgu@icmm.ac.cnBackground: Leukemia threatens so many lives around the world. Dihydroartemisinin (DHA), as a typical derivative of artemisinin (ART), can efficiently inhibit leukemia, but the controversial mechanisms are still controversial. Many reports showed that tumor cells acquire energy through the glycolysis pathway, pyruvate kinase M2 (PKM2) plays a crucial role in regulating glycolysis. However, it is unclear whether PKM2 or other key molecules are involved in DHA induced cytotoxicity in leukemia cells. Thus, this paper systematically investigated the anticancer effect and mechanism of DHA on human chronic myeloid leukemia K562 cells.Methods: In vitro, cytotoxicity was detected with CCK-8. Glucose uptake, lactate production and pyruvate kinase activity were investigated to evaluate the effect of DHA on K562 cells. To elucidate the cellular metabolism alterations induced by DHA, the extracellular acidification rate was assessed using Seahorse XF96 extracellular flux analyzer. Immunofluorescence, real-time PCR, and Western blotting were used to investigate the molecular mechanism.Results: We found that DHA prevented cell proliferation in K562 cells through inhibiting aerobic glycolysis. Lactate product and glucose uptake were inhibited after DHA treatment. Results showed that DHA modulates glucose uptake through downregulating glucose transporter 1 (GLUT1) in both gene and protein levels. The cytotoxicity of DHA on K562 cells was significantly reversed by PKM2 agonist DASA-58. Pyruvate kinase activity was significantly reduced after DHA treatment, decreased expression of PKM2 was confirmed in situ.Conclusion: The present study implicated that DHA inhibits leukemia cell proliferation by regulating glycolysis and metabolism, which mediated by downregulating PKM2 and GLUT1 expression. Our finding might enrich the artemisinins’ antitumor mechanisms.Keywords: tumor, leukemia, glycolysis, DHA, PKM2, GLUT1

Liyu Xu,1 Jie Zhang,2 Shanshan Shen,1 Xiufang Hong,1 Xingkun Zeng,1 Yinghong Yang,1 Zixia Liu,1 Lingyan Chen,1 Xujiao Chen1 1Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, People’s Republic of China; 2Department of Dentistry, Zhejiang Hospital, Hangzhou 310013, People’s Republic of ChinaCorrespondence: Xujiao ChenDepartment of Geriatrics, Zhejiang Hospital, Lingyin Road #12, Hangzhou 310013, People’s Republic of ChinaTel +86 18069897567Fax +86 0571 87985100Email lily197459@163.comPurpose: The study aimed to investigate the association between body composition and frailty in elder inpatients.Patients and Methods: This is a cross-sectional study including 656 elder inpatients (275 females and 381 males) aged ≥ 65 years, from department of geriatrics of Zhejiang Hospital between January 2018 and March 2019. Sociodemographic, health-related data and anthropometric measurements were evaluated. Body composition was assessed by bioimpedance analysis (BIA), mainly including skeletal muscle mass, body fat mass, total body water, fat-free mass,percent body fat, basal metabolic rate. Frailty was assessed by Clinical Frailty Scale (CFS). Univariate logistic regression was used to analyze the association between body composition and frailty.Results: Frailty was present in 43.9% of the participants. Frail inpatients showed higher waist circumference, body fat mass and percent body fat, non-frail inpatients showed greater upper arm circumference, calf circumference, skeletal muscle mass, total body water, fat-free mass and basal metabolic rate. Subjects with underweight (body mass index (BMI)< 18.5 kg/m2; odds ratio (OR), 95% confidence interval (CI)=4.146 (1.286– 13.368) P=0.017) and those with high waist circumference (OR 95% CI=1.428 (0.584– 3.491) P< 0.001), body fat mass (OR, 95% CI=1.143 (0.892– 1.315) P< 0.001) presented a higher risk of frailty compared to normal subjects. Skeletal muscle mass (OR; 95% CI=0.159 (0.064– 0.396) P< 0.001) was a protective factor for frailty.Conclusion: Frailty in elder Chinese inpatients was characterized by a body composition phenotype with underweight, high waist circumference, low skeletal muscle mass and high body fat mass. Underweight, abdominal obesity and sarcopenic obesity may, therefore, be targets for intervention of frailty.Keywords: frailty, elderly, skeletal muscle mass, body fat mass

Jian Cao,1,2,* Zhixu Liu,1,* Dongyang Ma,2 Shunyao Shen,1 Xudong Wang1 1Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai JiaoTong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, The 940th Hospital of People’s Liberation Army, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong WangDepartment of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai JiaoTong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel +86 21 53315159Email xudongwang70@hotmail.comPurpose: Although negative pressure wound therapy (NPWT) has been widely used in complicated wound care, there are still some obstacles regarding its use in the treatment of severe deep fascial space infections in the head and neck. The purpose of this study is to describe a new modified usage of NPWT and investigate the clinical efficacy of this system in a consecutive case series of severe deep fascial space infections.Methods: The investigators implemented a new modification of NPWT for the management of severe deep fascial space infections. In this new system, the half-plugged bar-shaped foam material was arranged along with the through-and-through side-holed latex drainage tube, which could maintain negative pressure in the distal part of the spaces, and the tube was easy to remove 5– 7 days after surgery. Twelve patients had severe deep fascial space infections in the head and neck with a direct threat to the airway. The median time of removal of the NPWT device, the median amount of drainage fluid and the median healing time were investigated.Results: A total of 7 male and 5 female patients with an average age of 63.2 years old were included in this study. The median time of removal of the NPWT device was 6 days (ranging from 4 to 7 days). The median amount of drainage fluid within 3 days after surgery was 420 mL (ranging from 280– 760 mL), and the median time for complete wound healing was 12 days (ranging from 10 to 21 days).Conclusion: The results of this study suggest that the modification of NPWT provides various advantages and leads to excellent clinical outcomes in the treatment of severe deep fascial space infections. Future studies will focus on the safety verification of portable usage and the cost effectiveness analysis of NPWT.Keywords: negative pressure wound therapy, severe deep fascial space infections, modified usage, head and neck

Zhiwei Chen,1,* Shengping Shen,1,* Wenbo Shi,1,* Gening Jiang,2 Xin Wang,3 Hong Jian,1 Zhen Zhou,1 Zhengping Ding,1 Shun Lu11Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, People’s Republic of China; 3Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workObjective: This multicenter, open-label, single-arm, phase II trial evaluated the efficacy and safety of an intercalated combination of erlotinib and gemcitabine/cisplatin or carboplatin in patients with stage IIIA non-small-cell lung cancer (NSCLC).Registration: This trial is registered with ClinicalTrials.gov, number NCT01297101.Methods: The primary endpoint was the objective response rate (ORR), which includes complete response (CR) and partial response (PR), assessed using RECIST version 1.0 in the intention-to-treat population. Adverse events (AEs) were graded by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Secondary endpoints included the disease control rate, disease-free survival (DFS), overall survival (OS), and safety. Between April 1, 2011, and July 31, 2014, 39 patients with stage IIIA NSCLC received two cycles of intercalated use of erlotinib with gemcitabine/cisplatin or carboplatin.Results: Eighteen patients (46.15%) achieved a PR and no patient achieved a pathologic CR, resulting in an ORR of 46.15% (95% CI 30–63%). Median DFS was 20 months (95% CI 5.26–50.61) and median OS was 25 months (95% CI 15.57–33.39). Patients with EGFR mutations (n=7) had a higher ORR than those with wild-type EGFR (n=9) (85.71% vs 55.56%, P=0.00). Most AEs were CTCAE grade 1 or 2; there were no cases of increased hematologic toxicity or erlotinib-emergent interstitial lung disease observed.Conclusion: Two cycles of intercalated neoadjuvant therapy with erlotinib and gemcitabine/cisplatin or carboplatin were effective and safe for patients with stage IIIA NSCLC. This approach should be further explored in larger randomized controlled trials given the lack of a consensus about the best treatment for stage IIIA NSCLC.Keywords: non-small-cell lung cancer, NSCLC, neoadjuvant, erlotinib, gemcitabine, platinum, objective response rate, progression-free survival, overall survival

Yue Hu,1,2,* Jingsi Mei,1,2,* Xiaofang Jiang,1,2 Ran Gu,1,2 Fengtao Liu,1,2 Yaping Yang,1,2 Hongli Wang,1,2 Shiyu Shen,1,2 Haixia Jia,3 Qiang Liu,1,2 Chang Gong1,21Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation; 2Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; 3Department of Breast Surgery, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workPurpose: To assess whether radiologist needs to rescan the breast lesion to validate the final American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) ultrasonography (US) assessment made on the static images in the diagnostic setting.Patients and methods: Image data on 1,070 patients with 1,070 category 3–5 breast lesions with a pathological diagnosis scanned between January and June 2016 were included. Both real-time and static image assessments were acquired for each lesion. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curves. The positive predictive values (PPVs) of each category in the two groups were calculated according to the ACR BI-RADS manual and compared. Kappas were determined for agreement on two assessment approaches.Results: The sensitivity, specificity, PPV, and negative predictive value for real-time US were 98.9%, 58.2%, 44.8% and 99.4%, and for static images were 98.9%, 57.1%, 44.1% and 99.3%, respectively. The performance of the two groups was not significantly different (areas under ROCs: 0.786 vs 0.780, P=0.566) if the final assessment was only dichotomized as negative (category 3) and positive (categories 4 and 5). All PPVs of each category for each assessment were within the reference range provided by the ACR in 2013 except subcategory 4B (reference range: >10% and ≤50%) of static image evaluation, which was also significantly higher than that of real-time assessment (54.8% vs 40.7%, P=0.037). The overall agreement of the two approaches was moderate (κ=0.43–0.56 according to different detailed assessment).Conclusion: Both static image and real-time assessment had similar diagnostic performance if only the treatment recommendations were considered, that is, follow-up or biopsy. However, as for subcategory 4B lesions without obviously benign or malignant US features, real-time scanning by the interpreter is recommended to obtain a more accurate BI-RADS assessment after assessing static images.Keywords: Breast Imaging Reporting and Data System, ultrasonography, diagnosis, real-time scanning

Xiufang Hong,1,2 Jing Yan,1 Liyu Xu,1 Shanshan Shen,1 Xingkun Zeng,1 Lingyan Chen1 1Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, People’s Republic of China; 2The Second School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, People’s Republic of China Objective: The definition of frailty still lacks quantitative biomarkers. This study aimed to investigate the relationship between nutrition-related biomarkers and frailty in hospitalized older patients.Materials and methods: This is a cross-sectional study including 380 hospitalized older patients. The patients were categorized as nonfrail (n=140), prefrail (n=81), and frail (n=159) by the criteria of frailty phenotype. The nutritional status was assessed using the mini nutritional assessment-short form (MNA-SF), levels of serum transferrin (TNF), prealbumin (PA), total protein (TP), albumin (ALB), retinol-binding protein (RBP), and hemoglobin (Hb).Results: The grip strength, levels of serum TFN, TP, ALB, Hb, and MNA-SF scores all decreased significantly in the order of nonfrail, prefrail, and frail groups (P

Jie Wang,1,* Xiaobo Bo,1,* Pinxiang Lu,2,* Tao Suo,1 Xiaoling Ni,1 Han Liu,1 Hongtao Pan,1 Sheng Shen,1 Min Li,1 Dexiang Zhang,2 Yueqi Wang,1 Houbao Liu1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of General Surgery, Xuhui Central Hospital, Shanghai, China *These authors contributed equally to this work Objective: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. Patients and methods: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan–Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. Results: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0–22.0 vs 8.0, 95% CI: 5.0–11.0 for median OS; 22.0, 95% CI: 13.0–33.0 vs 9.0, 95% CI: 5.0–11.0 for median CSS; both log-rank P

Huihua Qiu,1 Wenwei Ren,1 Yanjie Yang,2 Xiongzhao Zhu,3 Guangyun Mao,4 Shanping Mao,5 Yan Lin,6 Shanshan Shen,7 Changjin Li,8 Hongying Shi,4 Suo Jiang,8 Jingjing He,9 Ke Zhao,8 Ye Fu,10 Xiaoqu Hu,11 Yingying Gu,1 Kai Wang,12 Xiuchan Guo,13 Jincai He1,8 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Medical Psychology, Public Health Institute of Harbin Medical University, Harbin, People’s Republic of China; 3Medical Psychological Institute, Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Neurology, RenMin Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 7Department of Geriatrics, Zhejiang Hospital, Hangzhou, People’s Republic of China; 8Department of Psychology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 9Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 10Yinzhou Hospital Affiliated To Medical School of Ningbo University, Ningbo, People’s Republic of China; 11Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 12Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 13Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of China Purpose: Cognitive behavioral therapy (CBT) for depression had been found to be effective in reducing depressive and anxiety symptoms in breast cancer survivors. It is not known whether CBT for depression would also improve insomnia and quality of life (QOL). The aim of this study was to investigate whether CBT for depression would improve insomnia and QOL in a randomized controlled multicenter trial. Patients and methods: In this study, breast cancer survivors (n=392) were randomly allocated to the following three groups: CBT (n=98), self-care management (SCM, n=98), and usual care (UC, n=196) in a ratio of 1:1:2. CBT and SCM received a series of nine sessions for 12 weeks, whereas UC received UC only. Insomnia and QOL were evaluated using Athens Insomnia Scale (AIS) and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire at baseline, 4, 12, and 24 weeks. Results: There was a significant intergroup difference in AIS and FACT-B scores (both P

We provide several examples of Bayesian semiparametric regression analysis via the Infer.NET package for approximate deterministic inference in Bayesian models. The examples are chosen to encompass a wide range of semiparametric regression situations. Infer.NET is shown to produce accurate inference in comparison with Markov chain Monte Carlo via the BUGS package, but to be considerably faster. Potentially, this contribution represents the start of a new era for semiparametric regression, where large and complex analyses are performed via fast Bayesian inference methodology and software, mainly being developed within Machine Learning.

Xiang Zhu,* Yuxi Liu,* Hongfang Huang, Yonghua Zhang, Saisai Huang, Weiwei Zhou, Xiaocui Bian, Shiren Shen, Su Cao Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of China *These authors contributed equally to this work Purpose: Postoperative pain is a common clinical problem. In this study, we aimed to investigate the role of protein kinase C bII (PKCβII) in the progression of postoperative pain following skin/muscle incision and retraction (SMIR) surgery. Materials and methods: SMIR postoperative pain model was established in rats, akin to a clinical procedure. The expression level and location of p-PKCβII were observed in dorsal root ganglion (DRG) or spinal cord from SMIR-operated rats by Western blotting and immunofluorescence. In addition, the effects of PKCβII on the expression of protein gene product 9.5 (PGP9.5) or vascular endothelial growth factor (VEGF) were assessed by using pharmacological activator and inhibitor of PKCβII. Moreover, mechanical withdrawal threshold (MWT) was assessed before or after SMIR-operated rats were treated with inhibitor or activator of PKCβII. Results: The expression of PKCβII in DRG and spinal cord was significantly increased after SMIR surgery (P < 0.001, P < 0.01) and expression of PKCβII was located in the neurons of the spinal cord, and magnocellular neurons, non-peptide neurons, and peptide neurons in DRG. Besides, compared with skin/muscle incision group, retraction caused a marked increase in the expression of PKCβII and a significant decrease of MWT (P < 0.001, P < 0.05). The activator of PKCβII greatly increased the expression of PGP9.5 and VEGF (P < 0.05, P < 0.01) and enhanced MWT (P < 0.001), while inhibitor of PKCβII decreased the expression of PGP9.5 and VEGF and attenuated MWT (P < 0.05, P < 0.01, P < 0.001). Conclusion: Activation of PKCβII signaling pathways might be an important mechanism in the progression of postoperative pain. Keywords: postoperative persistent pain, neurons, PKCβII, PGP9.5, VEGF

Yanqiu Yu,1 Cheng Fang,2 Chunyan Peng,3,4 Shanshan Shen,4 Guifang Xu,4 Qi Sun,5 Lin Li,5 Chuan Su,6 Xiaoping Zou3,4 1Department of Gastroenterology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Gastroenterology, The Affiliated Drum Tower Clinical Medical School, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 5Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 6Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, People’s Republic of China Background: Gastric carcinoma (GC) is the third most frequent malignancy and the second most common cancer-related cause of death cause worldwide. Gastric intraepithelial neoplasia (GIN) is a well-documented precancerous lesion of GC. In this case–control study, we comprehensively explored the clinical and pathological characteristics of GIN, with the aim to identify its potential risk factors. Patients and methods: A total of 630 consecutive patients who underwent endoscopic submucosal dissection or mucosal resection for GIN were initially included. The detailed characteristics of all eligible patients and well-matched healthy controls were recorded and analyzed. Both univariate and multivariate logistic regression analyses were performed and presented with odds ratio (OR) and 95% confidential interval (CI), with additional subgroup analyses based on lesion location. Results: A total of 485 GIN-eligible patients were selected, among which 156 had proximal GIN. After follow-up, 434 patients with GIN and 310 age- and gender-matched healthy controls were included in the comparative analyses. Family cancer history (FCH); alcohol abuse; tobacco abuse; intake of high sodium, preserved food, spicy food, and less fruit; Helicobacter pylori (Hp) infection; and atrophic gastritis with intestinal metaplasia were more frequent in GIN patients. Thus, FCH (OR =3.485, 95% CI: 2.031–5.981), high sodium intake (OR =2.830, 95% CI: 1.645–4.868), less fruit intake (OR =4.082, 95% CI: 2.515–6.625), Hp infection (OR =2.307, 95% CI: 1.417–3.755), and atrophic gastritis with intestinal metaplasia (OR =15.070, 95% CI: 8.999–25.237) were independent risk factors for GIN. Further subgroup analyses demonstrated that the specific independent risk factor for proximal GIN was age (OR =2.001, 95% CI: 1.003–3.994), whereas that for distal GIN was intake of high sodium (OR =3.467, 95% CI: 1.896–6.338). Conclusion: This study reported a comprehensive overview of the clinical and pathological characteristics of GIN. FCH, high sodium intake, less fruit intake, Hp infection, and atrophic gastritis were identified as the independent risk factors for GIN. Keywords: gastric intraepithelial neoplasia, risk factor, case–control study, subgroup analysis

Antonio R Anzueto,1,2 Claus F Vogelmeier,3 Konstantinos Kostikas,4 Karen Mezzi,4 Sebastian Fucile,5 Giovanni Bader,4 Steven Shen,5 Donald Banerji,5 Robert Fogel5 1University of Texas Health Science Center, 2South Texas Veterans Healthcare System, University of Texas, San Antonio, TX, United States; 3Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.Methods: Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.Results: Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P

Yingchun Zhang,1,2,* Yunke Wang,1,* Chanchan Shen,1,2 Yingying Ye,1 Si Shen,1 Bingren Zhang,1,2 Jiawei Wang,1,2 Wei Chen,2 Wei Wang1,2 1Department of Clinical Psychology and Psychiatry, School of Public Health, 2Department of Mental Health, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Background: The relationship between normal personality and hypnotic susceptibility is important for understanding mental processing and mental disorders, but it is less consistent in normal people or in patients with a psychiatric disorder. We have hypothesized that the correlation exists but varies in individuals with different levels of hypnotizability. Participants and methods: We invited 72 individuals with high (HIGH group) and 47 individuals with low (LOW group) hypnotic susceptibilities to undertake tests of NEO-PI-R and the Stanford Hypnotic Susceptibility Scale, Form C (SHSSC). Results: The HIGH group scored significantly higher than the LOW group did on openness to experience and its facet openness to feelings. In the LOW group, SHSSC total was positively predicted by openness to ideas; age regression was positively predicted by openness to experience and negatively predicted by extraversion; anosmia to ammonia was negatively predicted by agreeableness; and negative visual hallucination was positively predicted by openness to experience. In the HIGH group, hallucinated voice was positively predicted by openness to experience and negatively predicted by agreeableness, and posthypnotic amnesia was positively predicted by extraversion and negatively predicted by openness to experience. Conclusion: The associations between normal personality traits and hypnotic susceptibility items were weak and different in the two groups, which imply that managing mental or somatoform disorders might be through adjusting hypnotizability and mobilizing personality functions. Keywords: hypnotic susceptibility, NEO-PI-R, normal personality trait, the Stanford Hypnotic Susceptibility Scale, Form C

Yingjia Sun, Xinghao Ai, Shengping Shen, Linping Gu, Shun Lu Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: To detect and analyze 13 cytokines that may be related to bone metastasis in the serum of non-small-cell lung cancer (NSCLC) patients with bone metastases and NSCLC patients with non-bone metastases.Patients and methods: The Luminex LiquiChip system was used to detect the concentration of 13 cytokines that may be related to bone metastasis in the serum of 30 NSCLC patients with bone metastases and 30 with non-bone metastases.Results: The concentration of insulin-like growth factor binding protein-3 (IGFBP-3) in the serum of NSCLC patients with bone metastases was obviously higher than in non-bone metastasis patients (P=0.014). The serum concentration of other cytokines showed no significant difference (P>0.05) between the two groups. The concentration of IGFBP-3 in the serum of the bone metastasis group was positively correlated to VEGF concentration (r=0.804, P=0.009) and monocyte chemotactic protein 1 (MCP-1) concentration (r=0.785, P=0.012), but had no correlation to other factors (P>0.05). No correlation was found between serum concentrations of cytokines in bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to the presence or absence of pain at diagnosis (r=0.701, P=0.036) and performance status (PS) score (r=0.670, P=0.048), and correlated with the number of bone metastases, sex, age, pathological characteristics, T stage, and N stage (P>0.05).Conclusion: The findings of this study suggest important clinical implications to detect the concentration of IGFBP-3 in the serum of lung cancer patients so as to evaluate the diagnosis and degree of bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to concentration of VEGF and MCP-1, which may be highly relevant for the development of new treatments for bone metastasis of lung cancer. Keywords: metastatic lung cancer, cytokine, liquichip

Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic. Keywords: ethosomes, transdermal drug-delivery systems, artesunate, febrifugine

Xi Wu,1 Zhinong Wang,2 Bo Hong,1 Shengjuan Shen,3 Yan Guo,4 Qinghai Huang,1 Jianmin Liu1 1Department of Neurosurgery, Changhai Hospital, Shanghai, People’s Republic of China; 2Department of Surgical Education, Changhai Hospital, Changzheng Hospital, Shanghai, People’s Republic of China; 3Department of Medical Education, The Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Internal Medicine, Changhai Hospital, Shanghai, People’s Republic of China Abstract: Disease treatments have been significantly influenced by the communications between patients, their families, and doctors the lack of which may lead to malpractice allegations and complaints. In particular, inadequate communication may delay diagnosis and treatment. Therefore, for doctors communication and interpersonal skills, are as important as clinical skills and medical knowledge. In this study we intended to develop two detailed communication content checklists and a modified interpersonal skills inventory, aiming to evaluate their integrity in the midst of communication skills assessments, to provide feedback for some participants, and to observe their communication competence in both aspects Keywords: standardized patient, communication skill, training, medical education, neurosurgeon