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Jiping Zhang,* Xianan Sang,* Yichao Yuan, Jiawei Shen, Yuanyuan Fang, Minjing Qin, Hangsheng Zheng, Zhihong Zhu College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 311402, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hangsheng Zheng; Zhihong Zhu, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email hs-zheng@163.com; zzhjanny@163.comBackground: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy-ϵ-pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo. Keywords: 4-deoxy-ϵ-pyrromycinone, lead compound, drug safety, drug efficacy, anti-tumor drug

Ying Zhang,1,* Xinxin Wang,1,* Xiaoqiao Sang,1,* Zhou Zhou,1 Guangrong Dai,1 Xiaobao Zhang1,2 1Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaobao Zhang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, Jiangsu, People’s Republic of China, Email hotdog100@163.comPurpose: Post-induction hypotension (PIH) is a common clinical phenomenon linked to increased morbidity and mortality in various non-cardiac surgeries. Patients with surgery in the afternoon may have preoperative hypovolemia caused by prolonged fasting and dehydration, which increases the risk of hypotension during the induction period. However, studies on the fluid therapy in early morning combating PIH remain inadequate. Therefore, we aimed to investigate the influence of prophylactic high-volume fluid in the early morning of the operation day on the incidence of PIH during non-cardiac surgery after noon.Patients and Methods: We reviewed the medical records of patients who underwent non-cardiac surgery after noon between October 2021 and October 2022. The patients were divided into two groups based on whether they received a substantial volume of intravenous fluid (high-volume group) or not (low-volume group) in the early morning of the surgery day. We investigated the incidence of PIH and intraoperative hypotension (IOH) as well as the accumulated duration of PIH in the first 15 minutes. In total, 550 patients were included in the analysis.Results: After propensity score matching, the incidence of PIH was 39.7% in the high-volume group and 54.1% in the low-volume group. Multivariate logistic regression analysis showed that patients in the high-volume group had lower incidence of hypotension after induction compared with the low-volume group (odds ratio, 0.55; 95% CI, 0.34– 0.89; p = 0.016). The high-volume fluid infusion in the preoperative morning was significantly correlated with the decreased duration of PIH (p = 0.013), but no statistical difference was observed for the occurrence of IOH between the two groups (p = 0.075).Conclusion: The fluid therapy of more than or equal to 1000 mL in the early morning of the surgery day was associated with a decreased incidence of PIH compared with the low-volume group in patients undergoing non-cardiac surgery after noon.Keywords: anesthesia induction, hypotension, fluid optimization, preoperative rehydration, hemodynamic instability

ChuoChuo Yu,1,* ZhiQun Liu,2,* Mingyang Zhao,3 Yanhui Liu,2 Yuxin Zhang,1 Ai Lin,2 Xiaohan Sang,1 Huan Wan2 1Department of Nursing, Hunan Normal University School of Medicine, Changsha, 410013, People’s Republic of China; 2Department of Nursing, The First Hospital Affiliated with Hunan Normal University (Hunan Provincial People`s Hospital), Changsha, 410005, People’s Republic of China; 3Operating Room, Guangzhou Dongsheng Hospital, Guangzhou, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan Wan, Department of Nursing, The First Hospital Affiliated with Hunan Normal University (Hunan Provincial People`s Hospital), No. 61 Jiefang West Road, Changsha City, Hunan Province, 410005, People’s Republic of China, Tel +86 137 8725 7287, Fax +86 731 8227 8012, Email huanwan3013@163.comObjective: To explore the influence of negative psychology and burnout in clinical nurses, and to analyse the mediating role between self-efficacy and emotional intelligence in emotion management.Methods: From January 2022 to December 2022, 12,704 clinical nurses from 32 general hospitals in Hunan Province were selected as research participants by convenience sampling. Negative psychology, emotion management, self-efficacy, emotional intelligence and burnout in clinical nurses were measured, and structural equation models were constructed to explore their impact on burnout in clinical nurses.Results: Clinical nurses’ negative psychology had a positive effect on burnout (β=0.60, 95% CI: 0.63– 0.66), emotional intelligence (β=˗0.08, 95% CI: ˗0.10, ˗0.06) and the self-efficacy of emotion management (β=− 0.60, 95% CI: ˗0.05, ˗0.03) on burnout. Moreover, emotional intelligence and emotion management self-efficacy played a mediating role between negative psychology and burnout in nurses.Conclusion: Clinical nurses’ negative psychology had a positive impact on burnout, and emotional intelligence and the self-efficacy of emotion management could alleviate the influence of negative psychology on burnout among nurses. Nurses’ emotional intelligence and emotion management self-efficacy can be improved through practical training to help them cope with emotionally loaded situations and reduce stress responses.Keywords: clinical nurse, job burnout, negative psychology, emotional management self-efficacy, emotional intelligence

Xuezhu Wang,1,&ast; Xu Yang,2,&ast; Jingnan Wang,1 Chengyan Dong,3 Jie Ding,1 Meiqi Wu,1 Yanyu Wang,2 Haiyan Ding,4 Hui Zhang,4 Xinting Sang,2 Haitao Zhao,2 Li Huo1 1Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3GE Healthcare China, Beijing, People’s Republic of China; 4Department of Biomedical Engineering, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Huo; Haitao Zhao, &num;1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Tel +86 13910801986; +86 13901246374, Email huoli@pumch.cn; zhaoht@pumch.cnPurpose: The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies.Patients and Methods: Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors.Results: Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥ 39.65 cm3 as the median value) was significantly associated with OS (P< 0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥ 1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P< 0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups.Conclusion: High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.Graphical Abstract: Keywords: unresectable hepatocellular carcinoma, PD-1 inhibitor, PD-L1 inhibitor, PET/CT, metabolic tumor volume, prognostic model

Jiayi Li,1,2,&ast; Qiao Chen,1,3,&ast; Lei Guo,4,&ast; Ji Li,5 Bao Jin,1 Xiangan Wu,1 Yue Shi,1 Haifeng Xu,1 Yongchang Zheng,1 Yingyi Wang,6 Shunda Du,1 Zhili Li,4 Xin Lu,1 Xinting Sang,1 Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 4Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China; 5Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 6Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Du; Zhili Li, Email dushd@pumch.cn; lizhili@ibms.pumc.edu.cnPurpose: To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification.Patients and Methods: We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student’s t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set.Results: Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4&ast;[m/z 436.2834] - 3.773&ast;[m/z 474.2626] + 3.82&ast;[m/z 661.4813] - 4.394&ast;[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985– 0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II.Conclusion: We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification.Keywords: intrahepatic cholangiocarcinoma, in situ lipids profiles, metabolomics, mass spectrometry, classification and diagnostic model

Bao Jin,1,&ast; Wenmo Hu,2,&ast; Si Su,2,&ast; Haifeng Xu,1 Xin Lu,1 Xinting Sang,1 Huayu Yang,1 Yilei Mao,1 Shunda Du1 1Department of Liver Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, People’s Republic of China; 2Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Du; Yilei MaoDepartment of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of ChinaEmail dushd@pumch.cn; pumch-liver@hotmail.comPurpose: We determined the prognostic value of the systemic inflammation response index (SIRI) in patients with cholangiocarcinoma after surgery and constructed a survival prediction model based on SIRI.Patients and Methods: We recruited 328 patients with histopathologically confirmed cholangiocarcinoma from 2003 to 2017 and performed Kaplan–Meier survival and Cox analyses to analyze the prognostic value of the SIRI and identify other significant factors. A nomogram involving SIRI and other clinicopathological factors was established based on the training cohort. The concordance index (C-index), decision curve analysis, calibration plots, and Hosmer–Lemeshow test were used to evaluate the clinical utility of the nomogram and to compare it with the traditional TNM staging system. The results were validated using a separate validation cohort.Results: The patients were randomly divided into the training (n = 232) and validation (n = 96) cohorts. In the training cohort, the independent factors derived from the Cox multivariate analysis were SIRI, platelet-to-lymphocyte ratio, jaundice, γ-glutamyl transpeptidase level, maximal tumor size, N stage, M stage, and radical surgery. Time-dependent receiver operating characteristic (ROC) curves showed higher AUC for SIRI than those for other inflammation-based biomarkers. A nomogram containing all the independent factors showed good discrimination and calibration. The C-index values for overall survival, 0.737 (95% Cl: 0.683– 0.791) and 0.738 (95% Cl: 0.679– 0.797) in the training and validation cohorts, respectively, were significantly better than those for the TNM staging system [0.576 (95% Cl: 0.515– 0.637) and 0.523 (95% Cl: 0.465– 0.581), respectively].Conclusion: SIRI was an independent prognostic factor for cholangiocarcinoma. A prognostic model based on SIRI might help clinicians to stratify patients more precisely and provide individualized treatment.Keywords: systemic inflammation response index, cholangiocarcinoma, prognosis, nomogram, survival

Rashid Menhas,1 Jianhui Dai,2 Muhammad Azeem Ashraf,3 Sohail M Noman,4 Sumaira Khurshid,5 Sajid Mahmood,6 Yu Weng,2 Rizwan Ahmad Laar,7 Xuehui Sang,2 Muhammad Kamran,8 Babar Shahzad,9 Waseem Iqbal9 1Research Center of Sports Social Sciences, School of Physical Education and Sports, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of China; 2School of Physical Education and Sports, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of China; 3Research Institute of Educational Science, Hunan University, Changsha, 410082, People’s Republic of China; 4Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China; 5School of Education and Science, Neijiang Normal University, Neijiang, Sichuan Province, People’s Republic of China, 641112; 6Department of Zoology, Hazara University, Mansehra, 21120, Pakistan; 7School of Sports Science and Physical Education, Nanjing Normal University, Nanjing, 210023, People’s Republic of China; 8NRSP Microfinance Bank Shorkot City Branch, Shorkot, 35050, Punjab, Pakistan; 9School of Energy, Soochow University, Suzhou, 215006, Jiangsu Province, People’s Republic of ChinaCorrespondence: Muhammad Azeem AshrafResearch Institute of Educational Science, Hunan University, Changsha, 410082, People’s Republic of ChinaEmail azeem20037@gmail.comBackground: China has the world’s largest population, going under health transition due to industrialization, urbanization, and a sedentary lifestyle. About 82% of China’s disease burden is due to the prevalence of non-communicable diseases (NCDs). Physical activity (active travel) is the best preventive measure against NCDs. The Chinese government has introduced several steps to improve national fitness and overcome NCDs among the aging population. Exercise and sports play a vital role in promoting physical activity and helpful in accomplishing the national fitness level for Healthy China under the national fitness plan (NFP).Objective: The current study aimed to explore the role of national fitness plan (NFP) in promoting physical activity and health well-being preventing NCDs under built environment intervention.Methods: The study was exploratory, and the mixed-method approach was used to analyze the primary and secondary data. Quantitative content analysis was used to analyze the collected data. A purposive sampling technique was used to collect the primary data from those individuals rich in knowledge about the National Fitness Plan (NFP) of China and its role in promoting physical activity for physical fitness.Results: The majority of the participants (32.0%) said that the national fitness plan helps promote sports environment and health. About 28.0% reported that NFP helps promote cycling and walk environments for physical activity and health promotion and preventing non-communicable diseases (NCDs).Conclusion: Participation in physical exercise and sports is the preferred approach to prevent different diseases. In the context of rising active living among the Chinese people, the facilities such as built environment and green parks under the national fitness plan (NFP) for sports play a crucial role in the mitigation of NCDs.Keywords: non-communicable diseases, physical activity, built environment, sports, national fitness

Zulkaif Ahmed Saqib,1 Jianhui Dai,2 Rashid Menhas,3 Shahid Mahmood,4 Maria Karim,5 Xuehui Sang,2 Yu Weng2 1Research Institute of Business Analytics & Supply Chain Management, College of Management, Shenzhen University, Shenzhen, Guangdong Province 518060, People’s Republic of China; 2School of Physical Education and Sports, Soochow University, Suzhou 215006, Jiangsu Province, People’s Republic of China; 3Research Center of Sports Social Sciences, School of Physical Education and Sports, Soochow University, Suzhou 215006, Jiangsu Province, People’s Republic of China; 4College of Management, Shenzhen University, Shenzhen, Guangdong Province 518060, People’s Republic of China; 5International Institute of Islamic Economics (IIIE), International Islamic University (IIU), Islamabad, 44000, Islamic Republic of PakistanCorrespondence: Jianhui DaiSchool of Physical Education and Sports, Soochow University, No. 50 Donghuan Road, Suzhou 215006 Jiangsu Province, People’s Republic of ChinaEmail sddjh@suda.edu.cnRashid MenhasResearch Center of Sports Social Sciences, School of Physical Education and Sports, Soochow University, No. 50 Donghuan Road, Suzhou 215006 Jiangsu Province, People’s Republic of ChinaEmail menhas.r@yahoo.comBackground: A modifiable risk factor for many diseases is physical inactivity. In this modern era, physical activity is acknowledged as a vital strategy to promote good health. According to the WHO, regular physical activity has various benefits for psycho-physical health. Decreased physical inactivity is happening in China due to the increased participation of the Chinese population in physical activity. The human body needs a specific level of physical activity to maintain good health.Objective: The main aim of the present study was to assess the Chinese people’s understanding of physical activity and participation in physical activity as a preventive measure against different diseases.Methods: The present study was exploratory and conducted in the Kunshan county-level city in Jiangsu Province, China. A well-designed questionnaire was used to collect the data from the survey participants. A total of 3390 residents were selected from 1300 households through a simple random sampling technique. The collected data were analyzed through SPSS software. Both univariate and bivariate analysis were performed.Results: The survey results showed that the majority of women are participating in physical activity. Most of the Kunshan people participate in physical activity one time or more than one time per week. They perform 30– 60 minutes of moderate-intensity physical activity to improve physical fitness, recreation, and disease prevention. Fitness walking is the most common type of physical activity among Kunshan people, and most of them participate in physical activity at night. Wilcoxon signed-rank test indicated that post-test ranks are statistically higher than pre-test ranks (P< 0.0039, 0.0039, 0.0039, 0.0020, 0.0001, 0.0156, 0.0313).Conclusion: The study results showed that physical activity plays a catalyst role in improving human health on a natural path. It reduces the risk factor of non-communicable diseases and promotes general wellbeing. These findings show that physical activity level increases in Chinese society as more people participate in physical activity for health-being.Keywords: physical activity, health, diseases, understanding, participation, wellbeing

Lejia Sun,1,* Dongyue Wang,2,* Mengyuan Zhang,2,* Yukai Jin,1 Bao Jin,1 Haifeng Xu,1 Shunda Du,1 Yiyao Xu,1 Haitao Zhao,1 Xin Lu,1 Xinting Sang,1 Shouxian Zhong,1 Huayu Yang,1 Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China; 2Peking Union Medical College (PUMC), PUMC & Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yilei Mao; Huayu YangDepartment of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing 100730, People’s Republic of ChinaTel +86-10-69156042Email pumch-liver@hotmail.com; dolphinyahy@hotmail.comPurpose: The immune prognostic index (IPI) has been used as a prognostic biomarker in various cancers. However, the prognostic value of the IPI in gallbladder cancer remains to be determined.Patients and Methods: This study included 139 patients who were diagnosed with gallbladder cancer after surgical resection from 2003 to 2017. We used a Kaplan–Meier curve analysis to evaluate the overall survival (OS). Cox proportional hazards regression methodology was used to identify significant independent prognostic factors. Prognostic nomograms for predicting OS were established to achieve superior discriminatory abilities. The prognostic nomograms were verified according to the concordance index, calibration curves, and decision curve analyses in the training cohort and validation cohort.Results: Of all 139 patients, 87 (62.6%) patients accepted R0 resection, 32% and 68% were stratified into the good and poor IPI group, respectively. The median OS was 55.9 (range, 5.93– 182.7) months in the good IPI group and 15.47 (range, 0.29– 190.37) months in the poor IPI group (P < 0.001). In the multivariate Cox model, the IPI was an independent predictor of OS along with the CA19-9, curative resection, and postoperative chemoradiotherapy. A nomogram based on these factors was efficient in predicting 1-, 3-, and 5-year survival probabilities. The nomogram showed higher sensitivity and specificity than the current cancer TNM staging system in the training cohort and validation cohort.Conclusion: The IPI is an independent prognostic factor in gallbladder cancer. Our IPI-based nomogram can serve as a useful and convenient prognostic tool for gallbladder cancer.Keywords: the immune prognostic index, gallbladder cancer, prognostic value, nomogram, overall survival

Qiao Chen,1,* Jiayi Li,1,2,* Bao Jin,1 Xiangan Wu,1 Yue Shi,1 Haifeng Xu,1 Yongchang Zheng,1 Yingyi Wang,3 Shunda Du,1 Xin Lu,1 Xinting Sang,1 Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this work.Correspondence: Shunda DuDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaEmail dushd@pumch.cnPurpose: We aimed to develop a nomogram for predicting the prognosis of patients with distal cholangiocarcinoma (DCC) and to compare its performance with that of the American Joint Committee on Cancer (AJCC) TNM system.Patients and Methods: To develop a nomogram, we collected the clinical data of 147 patients diagnosed with DCC who underwent pancreatoduodenectomy. Predictive accuracy and discriminative ability were determined using a concordance index and a calibration curve. Predictive performance was compared with that of a current staging systems for DCC.Results: Multivariate analysis revealed that jaundice, alcohol consumption, high fibrinogen, poorly differentiated tumor cells, positive lymph nodes, and positive margins were significantly associated with overall survival. These variables were incorporated into the nomogram. The concordance index of the nomogram for predicting overall survival was 0.737 (P< 0.001), which is significantly higher than the concordance index values (concordance index = 0.586) acquired using the AJCC TNM system (eighth edition). The calibration curve agreed well with predicted prediction and observed overall survival.Conclusion: We developed a nomogram for predicting the prognoses of patients with distal cholangiocarcinoma, which had superior practical clinical value compared with that of the AJCC TNM system.Keywords: distal cholangiocarcinoma, prognostic factors, nomograms, pancreatoduodenectomy, survival analysis

Weiyu Xu,1,* Xiaoqian Wu,2,* Xuezhu Wang,2,* Si Yu,2 Gang Xu,2 Jianping Xiong,3 Junwei Zhang,2 Xinting Sang,2 Yongchang Zheng,2 Wei Liu1 1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 2Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, People’s Republic of China; 3Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongchang ZhengDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), 1 Shuaifuyuan, Wangfujing, Beijing 100730, People’s Republic of ChinaEmail zhengyc_pumch@163.comWei LiuDepartment of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, 9 Dongdan Santiao, Dongcheng District, Beijing 100005, People’s Republic of ChinaEmail liuwei@ibms.cams.cnBackground: This study was designed to investigate the prognostic value of the lymphocyte to monocyte ratio (LMR) in patients with gallbladder carcinoma (GBC).Patients and Methods: We retrospectively enrolled 154 consecutive GBC patients from 2005 to 2017 in this study. The LMR of preoperative blood samples was calculated by dividing the lymphocyte count by the monocyte count. A receiver operating characteristic (ROC) curve was employed to identify the optimal cut-off value of the LMR in the determination of overall survival (OS). The Kaplan–Meier method was utilized to assess OS, and the Log rank test was employed to compare survival differences. Univariate and multivariate Cox regression analyses were conducted to detect independent prognostic indicators.Results: The optimal cut-off point for the LMR was 4.76 according to the ROC curve. Patients ≤ 60 years old with an LMR ≤ 4.76 experienced significantly worse OS than those with an LMR > 4.76 (hazard ratio (HR): 0.399, 95% confidence interval (CI): 0.265– 0.602, P< 0.001); however, the prognostic value of the LMR was not determined in patients > 60 years old or among the entire study cohort (both P> 0.05). Significantly poorer OS was observed in patients > 60 years with an LMR ≤ 4.21 compared to those with an LMR > 4.21 (HR: 1.830, 95% CI: 1.129– 2.967, P=0.014). Multivariate Cox regression analysis indicated that both the high and low LMR cut-off values were independent risk factors for OS (HR: 0.272, 95% CI: 0.105– 0.704, P=0.007; HR: 0.544, 95% CI: 0.330– 0.895, P=0.017).Conclusion: The LMR is an independent prognostic indicator for GBC patients, the cut-off value of which is age dependent.Keywords: gallbladder cancer, lymphocyte to monocyte ratio, LMR, survival, prognosis, biomarker

Jiayi Li, 1,* Qiao Chen, 1,* Bao Jin, 1 Yue Shi, 1 Xiangan Wu, 1 Haifeng Xu, 1 Yongchang Zheng, 1 Yingyi Wang, 2 Shunda Du, 1 Xin Lu, 1 Yilei Mao, 1 Xinting Sang 1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunda DuDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai-Fu-Yuan, Wang-Fu-Jing, Beijing 100730, People’s Republic of ChinaTel +86-139 1183 2900Fax +86-10-69156043Email dushd@pumch.cnPurpose: The aims of our study were to investigate the prognostic impact of the rate of preoperative serum carbohydrate antigen 19-9/bilirubin (CA19-9/BR) on patients with extrahepatic bile duct cancer.Patients and Methods: We collected clinical data from 89 patients who underwent surgery for extrahepatic cholangiocarcinoma (ECC) at Peking Union Medical College Hospital between January 2012 and December 2017. The Kaplan–Meier analysis for univariate analysis and the Cox proportional hazards models for multivariate analysis were used to determine possible independent prognostic factors.Results: CA19-9/BR was classified as elevated compared with normal based on the upper serum normal values of CA19-9 (37 U/mL) and bilirubin (1.5 mg/dL), which gives a cut-off at 25 U/mL/mg/dL. Univariate analysis showed that the overall survival of patients with a high CA19-9/BR ratio was significantly worse compared with patients with a low CA19-9/BR ratio (Hazard Ratio [HR] 2.149; 95% Confidence Interval [95% CI] 1.027– 4.495; P=0.042). Multivariate analysis revealed that a high CA19-9/BR ratio (HR 3.250; 95% CI 1.165– 9.067; P=0.024), low differentiation (HR 3.551; 95% CI 1.231– 10.244; P=0.019), and positive margin (HR 2.555; 95% CI 1.111– 5.875; P=0.027) remained independent prognostic factors after adjusting for age at diagnosis, maximal diameters, and other possible factors.Conclusion: The preoperative CA19-9/BR ratio is a good prognostic factor in predicting survival in ECC patients and closer follow-up is recommended in patients with a higher CA19-9/BR ratio before surgery.Keywords: prognosis, preoperative bilirubin-adjusted carbohydrate antigen 19-9, extrahepatic cholangiocarcinoma

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

Speckle simulation is a powerful protocol to investigate the properties of speckle and evaluate image processing method. However, only static speckle images can be simulated by available methods without considering time-integrated effect of CCD. A time–integrated dynamic speckle simulation method basedon coherent imaging was developed. Through the new simulation method, the effect of speckle size on LSCI was investigated. The smaller the speckle size is, the higher the spatial resolution become.But the one-dimensional speckle size should exceed two pixels to sample the speckle pattern. The characteristics of existing speckle contrast imaging methods were studied based on spatial statistics, and optimal parameters are given to obtain accurate and less noisy image. In general, the new simulation method for laser speckle imaging is a powerful tool to monitor blood flow in vivo and lay a solid foundation for the study of hemodynamics.

A novel auto-stereoscopic three-dimensional (3D) projection display system based on the frontal projection lenticular screen is demonstrated. It can provide high real 3D experiences and the freedom of interaction. In the demonstrated system, the content can be changed and the dense of viewing points can be freely adjusted according to the viewers’ demand. The high dense viewing points can provide smooth motion parallax and larger image depth without blurry. The basic principle of stereoscopic display is described firstly. Then, design architectures including hardware and software are demonstrated. The system consists of a frontal projection lenticular screen, an optimally designed projector-array and a set of multi-channel image processors. The parameters of the frontal projection lenticular screen are based on the demand of viewing such as the viewing distance and the width of view zones. Each projector is arranged on an adjustable platform. The set of multi-channel image processors are made up of six PCs. One of them is used as the main controller, the other five client PCs can process 30 channel signals and transmit them to the projector-array. Then a natural 3D scene will be perceived based on the frontal projection lenticular screen with more than 1.5 m image depth in real time. The control section is presented in detail, including parallax adjustment, system synchronization, distortion correction, etc. Experimental results demonstrate the effectiveness of this novel controllable 3D display system.

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones’ generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs. [ABSTRACT FROM AUTHOR]

Aimed at the problem that water droplets are easy to break up during the acceleration process in icing wind tunnel experiment, which makes it difficult for the particle size distribution of water droplets in the test section to conform to the icing weather conditions, the deformation and breakup regime of water droplets with a diameter of 100, 200, 400, 600, 800, 1 000 and 1 200 μm under the action of different air velocities(20, 50, and 80 m/s) are simulated by using the volume of fluid (VOF) method. The results show that under the action of 20 m/s air flow, the water droplet with a diameter of 600 μm does not break. Under the action of 50 m/s air flow, the water droplet with a diameter of 100 μm does not break. With the increase of Weber number, the wavelength of the most destructive wave also increases, and the breakup regime of water droplets changes from bag breakup to bag-plume breakup, to plume-shear breakup, and to shear breakup successively. The droplet breakup regime, including the bag breakup, bag/plume breakup, the plume/sheet-thinning breakup, and the shear breakup, has a significant effect on the ratio of the area of the largest droplet to the initial droplet. Under the condition that the initial drop diameter is the same, as the inlet velocity increases, the area ratio after breakup increases.

Mei-Yu Lv,1,2 Ling-Ling Jin,2,3 Xi-Qiao Sang,2 Wen-Chao Shi,2 Li-Xia Qiang,2 Qing-Yan Lin,4 Shou-De Jin2 1Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, 150001, People’s Republic of China; 2Department of Respiratory Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 3Department of Critical Care medicine, the Second Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an, Shaanxi, China; 4Department of Respiratory Medicine, Heilongjiang Provincial Hospital, Harbin, 150001, People’s Republic of ChinaCorrespondence: Shou-De Jin, Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 Yiyuan Street, Nangang District, Harbin, 150001, People’s Republic of China, Tel/Fax +86 0451-85939123, Email jinshoude@163.comPurpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-β regulation.Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-β, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers.Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-β was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-β, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon.Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-β. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.Keywords: alpha/beta hydrolase 2, COPD, TGF-β, airway remodeling, EMT

【Objective】 The fruit radish is a cash crop commonly cultivated in greenhouses in central and northern China. This study aims to determine the most effective drip irrigation schedule to enhance its yield while simultaneously increasing water use efficiency. 【Method】 The cultivar “Ice Cream” was used as the model plant. The irrigation was based on soil matric potential measured at the depth of 20 cm in that whenever it dropped to -10 (T1), -20 (T2), -30 (T3), -40 (T4) or -50 kPa (T5), we irrigated the crops by 10 mm of water. In each treatment, we measured the growth, yield and quality, as well as irrigation water use efficiency (IWUE) of the crop. 【Result】 The total irrigation amount for T1-T5 decreased from 120 to 70 mm. Reducing the soil matric potential threshold for irrigation resulted in reductions in area and fresh weight of leaves, root diameter and length, and weight of the radish, albeit the reduction in root length was not significant. Compared with T1, T2—T5 increased the yield by 2.2% to 44.0%, T2 increased IWUE by 17.3%, and T3—T5 reduced IWUE by 4.1% to 6.6%. With the decrease in the soil matric potential threshold, the soluble solid content and electrical conductivity of the radish both increased first followed by a decline, the soluble solid content peaked in T2 and Vc content increased monotonically. 【Conclusion】 Setting soil matric potential at depth of 20 cm at -20 kPa as the threshold and the irrigating 10 mm of water each time is optimal for improving the yield and IWUE of greenhouse fruit radish.

Sea cucumber, an important marine food and medicinal resource, contains polysaccharides, which are one of the most important active substances in it. Sulfate groups play an important role in the biological activity of polysaccharides, and sea cucumber sulfated polysaccharides may specifically affect the growth of certain intestinal microorganisms and the production of related metabolites due to their different chemical structures, which contribute to the variable health promoting effects. As a complex ecosystem of the human body, the intestinal flora plays an irreplaceable role in life activities such as nutritional metabolism. Sea cucumber sulfated polysaccharides can be used as prebiotics to alleviate diseases caused by intestinal flora disorder by regulating its composition. This review article summarizes the structures of sea cucumber sulfated polysaccharides, with a focus on the latest progress in research on their influence on glycolipid metabolism through the gut microbiota. These studies will contribute to a better understanding of the health promoting mechanism of sea cucumber sulfated polysaccharides and provide a scientific basis for their application in functional foods.

Back electromotive force (EMF)-based sliding mode observer (SMO) is increasingly employed for interior permanent magnet synchronous machine (IPMSM) sensorless drives due to its high robustness to external disturbance and low sensitivity to system parameter variations. However, its control performance is severely weakened by the inherent chattering and speed iteration operation. In order to effectively resolve these problems, a strategy to design a dual-SMO is proposed in this paper. With the proposed strategy, the combination of the stator-voltage transformation matrix (SVTM) and the low-pass filter is developed to obtain the rotor position information, which greatly alleviates the chattering without any deviations. Meanwhile, three independent equations are constructed and extracted by placing two SVTMs in different locations. By solving these three equations, the rotor position can be calculated directly with zero phase shift, which eliminates the speed iteration operation and improves the system’s dynamic performance. Furthermore, by analyzing the influences of machine parameters’ variations, the suitable virtual q-axis inductance can be selected to quickly achieve the optimal-efficiency sensorless control of the IPMSM. Finally, the experimental results on an IPMSM demonstrate that the rotor position with good steady-state and dynamic performance can be obtained accurately by using the proposed sensorless control strategy.