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Li Yang,1 Jing Yang,2 Guosen Bu,3 Rui Han,1 Jiamila Rezhake,1 Xiaolin La1 1Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of China; 2Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Xiaolin La, Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushannan Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362889, Email 909232905@qq.comPurpose: Screening of pathological copy number variations (CNVs) is important for early-diagnosis of hereditary disease. This study was designed to investigate the efficiency of non-invasive prenatal testing (NIPT) in detecting fetal CNVs.Methods: This retrospective analysis included fetuses with CNVs between January 2018 and December 2020. Karyotype analysis and CNV sequencing (CNV-seq) were performed. We then analyzed the positive predictive values of the subchromosomal microdeletions and microduplications.Results: Fifty-eight subjects with aberrant CNVs were screened after NIPT, among which 44 finally underwent amniocentesis. CNV-seq confirmed the presence of CNVs in 24 cases. This indicated that false positivity rate of NIPT was 45.5%. Among 24 cases with CNVs after CNV-seq, only 4 showed consistent findings with karyotype analysis, which showed that karyotyping analysis yielded a missed diagnosis rate of 83.3% for the genome CNV. Positive predictive value (PPV) was 50.0% for CNVs with a length of < 5 Mb after NIPT screening. PPV for CNVs with a length of 5 Mb-10 Mb was 33.3%, while that for CNVs with a length of ≥ 10Mb was 60%. For CNVs duplication after NIPT, the PPV was 65.2%, while that for deletion was 36.4%.Conclusion: For CNVs detected after NIPT, it should be combined with ultrasonographic findings, karyotype analysis, CNV-seq or CMA to determine the pregnancy outcome. Expanding NIPT may increase the risk of unnecessary invasive surgery and unintended selective termination of pregnancy.Keywords: non-invasive prenatal screening, genome copy number variation, next-generation sequencing, prenatal diagnosis

Ruyu Han,1,&ast; Leijuan Gan,1,&ast; Liyu Sun,1 Mengran Lang,2 Xindi Tian,1 Kangwei Zhu,1 Lu Chen,1 Guangtao Li,1 Tianqiang Song1 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 2Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-22-23340123, Fax +86-22-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data.Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently.Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.Keywords: hepatocellular carcinoma, conversion therapy, recurrence-free survival, hepatic resection

Yang Chong,1,2 Dong Yu,1,2 Rui Han,3 Yanxu Li,2 Yali Gu,3 Zhaoyu Lu,1,2 Fengsong Nie,1,2 Lingli Wang,1 Hengmi Cui4 1Department of Traditional Chinese Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 2Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 4Institute of Epigenetics and Epigenomics and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of ChinaCorrespondence: Yang Chong, Department of Traditional Chinese Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China, Email 092016@yzu.edu.cn Hengmi Cui, Institute of Epigenetics and Epigenomics and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China, Email hmcui@yzu.edu.cnPurpose: Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing.Patients and Methods: Luvangetin nanoemulsions were prepared by high-speed shear method and characterized based on their appearance structure, average droplet size, polydispersity index (PDI), electric potential, storage stability. Optimized formulation of luvangetin nanoemulsion by Box-Behnken design (BBD). The antimicrobial activity and antimicrobial mechanism of luvangetin nanoemulsions against common hospital pathogens, ie, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were investigated using luvangetin nanoemulsions. The biosafety of luvangetin nanoemulsion was evaluated through cytotoxicity, apoptosis, and reactive oxygen species (ROS) assay experiments using human normal epidermal cells and endothelial cells. Finally, the effect of luvangetin nanoemulsion on healing of infected wounds was investigated in B6 mice.Results: Luvangetin nanoemulsion formulation consists of 2.5% sunflower seed oil, 10% emulsifier Span-20 and 7 minutes of shear time, and with good stability. Luvangetin nanoemulsion produces antibacterial activity against S. aureus and E. coli by disrupting the structure of bacterial cell membranes. Luvangetin nanoemulsion are biologically safe for HaCat and HUVEC. Luvangetin nanoemulsion showed good therapeutic effect on MRSA infected wounds in mice.Conclusion: For the first time, developed a new formulation called luvangetin nanoemulsion, which exhibited superior antibacterial effects against Gram-positive bacteria. Luvangetin nanoemulsion has a favorable effect in promoting infected wound healing. We have combined luvangetin, which has multiple activities, with nanoemulsions to provide a new topical fungicidal formulation, and have comprehensively evaluated its effectiveness and safety, opening up new possibilities for further applications of luvangetin. Keywords: luvangetin, nanoemulsion, antimicrobial mechanism, infected wound healing

Rui Han,1,2 Xiwu Rao,3 Huiling Zhou,4 Lingeng Lu5– 7 1Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Chinese Medicine, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Oncology, The First Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China; 5Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA; 6School of Medicine, Center for Biomedical Data Science, Yale University, New Haven, CT, USA; 7Yale Cancer Center, Yale University, New Haven, CT, USACorrespondence: Rui Han, Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email dianxiqiao@foxmail.comAbstract: The utilization of PD-1/PD-L1 inhibitors marks a significant advancement in cancer therapy. However, the efficacy of monotherapy is still disappointing in a substantial subset of patients, necessitating the exploration of combinational strategies. Emerging from the promising results of the KEYNOTE-942 trial, RNA-based therapies, particularly circRNAs and piRNAs, have distinguished themselves as innovative sensitizers to immune checkpoint inhibitors (ICIs). These non-coding RNAs, notable for their stability and specificity, were once underrecognized but are now known for their crucial roles in regulating PD-L1 expression and bolstering anti-cancer immunity. Our manuscript offers a comprehensive analysis of selected circRNAs and piRNAs, elucidating their immunomodulatory effects and mechanisms, thus underscoring their potential as ICIs enhancers. In conjunction with the recent Nobel Prize-awarded advancements in mRNA vaccine technology, our review highlights the transformative implications of these findings for cancer treatment. We also discuss the prospects of circRNAs and piRNAs in future therapeutic applications and research. This study pioneers the synergistic application of circRNAs and piRNAs as novel sensitizers to augment PD-1/PD-L1 inhibition therapy, demonstrating their unique roles in regulating PD-L1 expression and modulating immune responses. Our findings offer a groundbreaking approach for enhancing the efficacy of cancer immunotherapy, opening new avenues for treatment strategies. This abstract aims to encapsulate the essence of our research and the burgeoning role of these non-coding RNAs in enhancing PD-1/PD-L1 inhibition therapy, encouraging further investigation into this promising field.Keywords: CircRNA, piwi-RNA, immunotherapy, PD-1/PD-L1 blockade, immunotherapy sensitizer, combination therapy

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Ruyu Han,&ast; Leijuan Gan,&ast; Mengran Lang,&ast; Guangtao Li, Lu Chen, Xindi Tian, Kangwei Zhu, Liyu Sun, Tianqiang Song Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-022-23340123, Fax +86-022-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease.Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19– 9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients’ RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91).Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.Keywords: nomogram, Barcelona clinic Liver cancer system, recurrence-free survival, hepatic resection, radiofrequency ablation

Jinpeng Shi,1,&ast; Jiayu Li,1,&ast; Haowei Wang,1,&ast; Xuefei Li,2 Qi Wang,1 Chao Zhao,2 Lei Cheng,2 Ruoshuang Han,1 Peixin Chen,1 Haoyue Guo,1 Zhuoran Tang,1 Caicun Zhou,1 Zhemin Zhang,1 Fengying Wu1 1Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengying Wu; Zhemin Zhang, Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, No. 507, Zheng Min Road, Shanghai, 200433, People’s Republic of China, Tel +86 21 6511 5006, Email fywu@163.com; zhemindoc@163.comPurpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.Materials and Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy. Keywords: tumor-associated neutrophil, single-cell RNA-sequencing, non-small cell lung cancer, tumor microenvironment, heterogeneity

Ruixia Han1,2 1School of Media and Communication, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Institute of Cultural Innovation and Youth Development, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of ChinaCorrespondence: Ruixia Han, School of Media and Communication, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China, Tel +86-21-34202854, Fax +86-21-34202854, Email annahan08@sjtu.edu.cnIntroduction: Do more friends and more frequent interactions on social media result in more social support? The impact of variables such as interaction size and frequency on the social support individuals receive via social platforms has been studied from the perspective of social networks, and some studies have focused on the role of interaction topics from the perspective of private engagement. Little research has been done on the impact of affect control embedded in social networks. The emotion-first nature of social media and the rise of affect control theory mean that this perspective deserves attention.Methods: This study examined 634 WeChat users by means of an online survey on variables related to social media use, such as social network size, interaction frequency, users’ evaluation of network members, and personal topic involvement, and then tested the influencing mode of these variables on people’s perceived social support through chain mediation analysis using Model 80 of the process in spss.Results: (1) Interaction size influences perceived social support by affecting personal topic involvement; (2) Interaction frequency does not directly mediate the relationship between interaction size and perceived social support, but mediates the relationship in a chain by affecting personal topic involvement; and (3) Social network evaluation not only directly mediates the relationship between interaction size and perceived social support, but also further mediates the relationship by influencing personal topic involvement.Conclusion: The study confirmed the role of affective control in people’s perceived social support through social network interactions. Those people talk about personal matters with individuals who have greater evaluation, potency, and activity in social networks are more likely to get perceived social support. The study draws our attention to the role of affection control in interpersonal relationships in the era of social media mediating people’s daily interactions.Keywords: social media, social interaction, social support, interaction frequency, EPA

Rongfeng Han, Lijun Duan, Yang Zhang, Xia Jiang Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Rongfeng Han, Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of China, Email hanmenghappy@126.comBackground: Type 2 diabetes mellitus (T2DM) patients are likely to develop kidney disease. Early diagnosis, finding predictors and controlling risk factors are of great significance for T2DM patients. This study investigated the ability of uric acid (UA), the uric acid to creatinine (CR) ratio (UA/CR) and the uric acid to high-density lipoprotein cholesterol ratio (UHR) to assess the kidney function of T2DM patients and determined the relationship between the three indicators and the estimated glomerular filtration rate (eGFR).Methods: A total of 1326 adult T2DM patients were enrolled in the current study. Patients were stratified into three groups according to their eGFRs. Spearman correlation was used to analyze the correlation between three indicators and the clinical variables. Logistic regression analysis was used to assess the association between the three indicators and diabetic kidney disease (DKD) and kidney impairment (eGFR < 60 mL/min/1.73 m2). Receiver operating characteristic (ROC) analyses and the area under the ROC curve (AUC) were then used to assess the ability of UA, UA/CR, and UHR to discriminate kidney impairment in T2DM.Results: UA and UHR demonstrated a positive association with DKD risk (P < 0.05). The odds ratios (ORs) were 1.005 (95% CI, 1.004– 1.007) and 1.057 (95% CI, 1.039– 1.076), respectively. UA/CR was negatively correlated with DKD risk (OR, 0.922 (95% CI, 0.876, 0.970), P < 0.05). Furthermore, UA and UHR demonstrated a strong positive association with kidney impairment risk, while UA/CR was negatively correlated with kidney impairment risk in T2DM patients (P < 0.05 for all) after adjusting for confounding factors. UA had the highest AUC (0.762) among the three indicators. UHR had a greater AUC (0.713) than UA/CR, which had an AUC value of 0.148 (p < 0.001).Conclusion: UA is the best indicator of renal impairment (eGFR < 60 mL/min/1.73 m2) among the three indicators, and UHR is a better indicator than UA/CR.Keywords: type 2 diabetes mellitus, T2DM, uric acid, UA, uric acid to creatinine ratio, UA/CR, uric acid to high-density lipoprotein cholesterol ratio, UHR, estimated glomerular filtration rate, eGFR

Zhaoxia Xu,1,&ast; Lei Zhang,2,&ast; Ran Han,1 Chengwei Ding,1 Haochang Shou,1 Xueguang Duan,1 Shengwei Zhang1 1Department of Clinical Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueguang Duan; Shengwei Zhang, Department of Clinical Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +86 13911179092 ; +86 13124780206, Email duanxg714@163.com; zswo6@aliyun.comBackground: Candida auris is a pathogen first found in external ear canal, becoming a major threat to global health. Here, we describe a candidemia case caused by a novel drug-resistant Candida auris strain.Case Presentation: An 80-year-old patient, with multiple serious medical conditions, was suffered from candidemia caused by Candida auris, died 9 days after admission in our hospital. Phylogenetic analysis indicates that this C. auris isolate (designated BJCA003) belongs to the South Asian clade, carries the Y132F mutation in the protein Erg11. And antibiotic susceptibility test indicated that BJCA003 is resistant to fluconazole and amphotericin B, not susceptible to caspofungin. In addition, this strain has multiple colony and cellular morphologies under different culture conditions.Conclusion: Strain BJCA003 is a novel drug resistant C. auris strain in mainland China, the Y132F mutation in Erg11 may attribute to fluconazole-resistance, alarming that we still face more challenges about C. auris.Keywords: Candida auris, candidemia, drug-resistant, mutation, morphologies

Leijuan Gan,1– 3,&ast; Mengran Lang,1– 4,&ast; Xindi Tian,1– 3 Shaohua Ren,1– 3 Guangtao Li,1– 3 Yayue Liu,1– 3 Ruyu Han,1– 3 Kangwei Zhu,1– 3 Huikai Li,1– 3 Qiang Wu,1– 3 Yunlong Cui,1– 3 Wei Zhang,1– 3 Feng Fang,1– 3 Qiang Li,1– 3 Tianqiang Song1– 3 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 4Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang, Hebei, 065001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Tel +86-022-23340123, Fax +86 022-23537796, Email songtianqiangtj@163.comPurpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC).Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2– 47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥ 3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments.Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.Keywords: lenvatinib, sintilimab, conversion therapy, unresectable hepatocellular carcinoma, TACE, HAIC

Fei Guo,1,&ast; Yuting Yan,1,&ast; Li Sun,1 Ruili Han,1 Lanlan Zheng,1 Yuan Qin,1 Shuang Wang,1 Xude Sun,1 Zhaohua Ji,2 Changjun Gao1 1Department of Anesthesiology, Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjun Gao, Department of Anesthesiology, Second Affiliated Hospital of Air Force Medical University, Xin Si Road & 569, Xi’an City, Shaanxi, 710038, People’s Republic of China, Tel/Fax +86 2984777439, Email gaocj74@163.com Zhaohua Ji, Department of Epidemiology, School of Public Health, Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, ChangLe Road & 169, Xi’an City, Shaanxi, 710032, People’s Republic of China, Tel/Fax +86 2884711316, Email hellojzh@msn.comObjective: This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for postoperative delirium (POD) in surgical patients.Methods: Based on database searches of the Wanfang, China National Knowledge Infrastructure (CNKI), VIP, Chinese Biology Medicine (CBM), PubMed, Cochrane Library, and Web of Science, relevant RCTs published before December 30, 2022, were extracted. Outcome indicators included the incidence of POD, changes in Confusion Assessment Method (CAM) scores, Visual Analogue Scale (VAS) scores, and the intraoperative consumption of anesthetics. Data were pooled and analyzed by Review Manager 5.3, and publication bias detection was conducted using Stata 17.0.Results: A meta-analysis containing 715 experimental and 717 control participants from 12 RCTs was performed. The overall results showed that TEAS had obvious superiority with a lower incidence of POD on any day during the postoperative 1 week. In subgroup analyses, the CAM scores on the third postoperative day were significantly lower in the TEAS group than in the control group (MD = − 0.52, 95% CI: − 1.02 to − 0.03, P = 0.04), the VAS scores on the first postoperative day were significantly lower in the TEAS group than in the control group (MD = − 0.19, 95% CI: − 0.36 to − 0.02, P = 0.03), the consumption of propofol and remifentanil were both significantly lower in the TEAS group compared with the control group (MD = − 23.1, 95% CI: − 37.27 to − 8.94, P = 0.001; MD = − 105.69, 95% CI: − 174.20 to − 37.19, P = 0.002). No serious adverse events of TEAS were reported in any of the referenced studies.Conclusion: TEAS has an obvious curative effect in preventing POD and pain in the earlier stage of surgical patients. It could be a promising assisted anesthesia technique in the future.Keywords: transcutaneous electrical acupoint stimulation, TEAS, postoperative delirium, POD, meta-analysis

Ruiqi Han,1 Wenjuan Zhang,2 Lina Zhang,3 Jinghua Zou,1 Yanran Yang,1 Hongkun Li,1 Jun Zhang1 1Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Orthodontics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Orthodontics, Faculty of Stomatology, Liaocheng People’s Hospital, Liaocheng, People’s Republic of ChinaCorrespondence: Jun Zhang, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, 250012, Tel +86 13953109816, Email zhangj@sdu.edu.cnPurpose: To investigate the roles of Notoginsenoside R1 (NG-R1) on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and explore its possible mechanism.Methods: hPDLSCs were isolated and, then characterized by flow cytometry. Cell-counting kit-8 (CCK-8) and colony assays were used to validate the effect of different NG-R1 concentrations on hPDLSCs proliferation and the optimal concentration was determined. Quantitative detection of alkaline phosphatase (ALP) activity at optimal concentration and the mineralization of the cells was investigated by Alizarin Red S staining. qRT-PCR and Western blot were utilized to examine the factors expression levels of ALP, Runx Family Transcription Factor 2 (RUNX2), Collagen I (Col-1) and catenin beta 1 (CTNNB1; β-catenin). In addition, the tankyrase inhibitor XAV-939 was used to explore NG-R1’s role in canonical Wnt signaling.Results: hPDLSCs were positive for surface antigens CD90 while negative for CD34 and CD45, which indicated that we have successfully isolated the hPDLSCs. Furthermore, a concentration of 20μmol NG-R1 dramatically enhanced hPDLSCs proliferation, ALP activity, and mineral deposition. ALP, RUNX2, COL-1, and β-catenin expression were all rised in comparison to control group. After XAV-939 was added to disrupt the canonical Wnt signaling, the impact of NG-R1 appeared to be reversed.Conclusion: These findings suggest that NG-R1 can stimulate osteogenic differentiation of hPDLSCs, which is probably attributable to canonical Wnt signaling activation.Keywords: notoginsenoside R1, NG-R1, human periodontal ligament stem cells, hPDLSCs, osteogenesis, β-catenin

Hongkun Li, Yilin Li, Jinghua Zou, Yanran Yang, Ruiqi Han, Jun Zhang Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Jun Zhang, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, 250012, People’s Republic of China, Tel +86 139 5310 9816, Email zhangj@sdu.edu.cnPurpose: To investigate the effects of sinomenine on orthodontic tooth movement and root resorption in rats, as well as the effect of sinomenine on the osteogenesis of periodontal ligament stem cells (PDLSCs).Methods: Fifty-four male Wistar rats were randomly divided into 3 groups: control group, 20 mg/kg sinomenine group and 40 mg/kg sinomenine group. Fifty-gram orthodontic force was applied to all groups. Each group was injected intraperitoneally with corresponding concentration of sinomenine every day. After 14 days, all rats were sacrificed. Micro-computed tomography (micro-CT) scan was used to analyze tooth movement, root resorption and alveolar bone changes. The effect on periodontal tissue was analyzed by Masson, tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining. In vitro, PDLSCs were extracted and identified. The effect of sinomenine on proliferation was determined by cell-counting kit-8. The effect of sinomenine on osteogenesis was investigated by alkaline phosphatase (ALP) activity and alizarin red staining. qPCR and Western blotting were performed to explore the effects of sinomenine on the expression levels of ALP, runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG).Results: The tooth movement and root resorption of sinomenine groups were reduced. Sinomenine decreased trabecular spacing on compression side and increased alveolar bone volume and trabecular thickness on tension side. TRAP-positive cells in sinomenine groups decreased significantly. The expressions of TNF-α and RANKL were decreased, while the expressions of OPG, RUNX2 and osteocalcin were up-regulated. In vitro, 0.1 M and 0.5 M sinomenine enhanced ALP activity, mineral deposition and the expression of ALP, RUNX2 and OPG, and reduced the expression of RANKL.Conclusion: Sinomenine could inhibit tooth movement, reduce root resorption, and exert a positive effect on bone formation in rats. Moreover, sinomenine promoted the osteogenesis of PDLSCs.Graphical Abstract: Keywords: sinomenine, tooth movement, root resorption, osteoclast, osteogenesis

Yuan Zhang,1,&ast; Hongli Yue,1,&ast; Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,&ast; 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Leijuan Gan,&ast; Shaohua Ren,&ast; Mengran Lang,&ast; Guangtao Li, Feng Fang, Lu Chen, Yayue Liu, Ruyu Han, Kangwei Zhu, Tianqiang Song Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China, Email songtianqiangtj@163.comPurpose: This study aimed to explore the relationship between the tumor marker score (TMS) and the postoperative recurrence of single small hepatocellular carcinoma (HCC).Patients and Methods: A total of 409 patients with one resectable HCC with a diameter of 3 cm or less who visited Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2014 were included in this study. Their alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) levels were classified into low and high groups using X-tile software. Each patients’ TMS was calculated as the sum of each tumor marker (low = 0; high = 1).Results: A total of 142 patients were classified as TMS0, 171 as TMS1, and 96 as TMS2. Kaplan–Meier analysis illustrated that TMS could divide the patients into groups with remarkably different prognoses, and the patients with high TMS had worse recurrence-free survival (RFS) than those with low TMS. Multivariate analysis showed that TMS, age, and HBeAg positive were the independent predictors of RFS rate. Subgroup analysis revealed that high TMS was a stable risk factor relative to TMS0. Receiver operating curves showed that the 1-, 3-, and 5-year area under curve (AUC) values of TMS were 0.698, 0.662, and 0.673, respectively. The AUC of TMS was higher than that of other common prognostic models in time-dependent receiver operating curve.Conclusion: TMS was an independent prognostic factor for the postoperative recurrence of a single small HCC and can provide a well-discriminated risk stratification, thus contributing to prognostic prediction and adjuvant therapeutic development.Keywords: hepatocellular carcinoma, recurrence-free survival, tumor marker score, alpha-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9

Ruixia Han,1,2 Jian Xu1– 3 1School of Media and Communication, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Institute of Cultural Innovation and Youth Development, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 3Institute for Urban Governance, Shanghai Jiao Tong University, Shanghai, 200052, People’s Republic of ChinaCorrespondence: Ruixia Han; Jian Xu, School of Media and Communication, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China, Tel/Fax +86 21-34202854, Email annahan08@sjtu.edu.cn; xujian@sjtu.edu.cnIntroduction: Based on the cognitive-affective model, this paper examines how social media affects the public cognitive and affective factors, further influence their attitudes towards COVID-19 governance policy.Methods: Through an online survey, we measured individual COVID-19 policy attitude, social media use and other related factors of 1222 respondents from 12 countries, and based on this, we carried out regression and mediation analysis on the data to obtain the research results.Results: From the perspective of cognitive factors, the public perception of the severity of the COVID-19 itself does not significantly affect their attitudes towards governance policy. On the contrary, the evaluation on government governance performance, risks and governance anticipations have more significant impacts. Among the affective factors, personal anxiety and patriotism significantly affect the formation of public attitudes, personal anxiety is positively correlated, and patriotism is negatively correlated. It is important to note that nationalism has no significant influence on public attitudes to COVID-19 policy on a global scale.Conclusion: (1) Social media influences the public COVID-19 policy attitudes through their moderating effect on affective and cognitive factors. (2) The impact of social media on affective pathways is more significant than that on cognitive pathways. (3) The positive moderating effect of social media on patriotism obscures the tendency of strict governance of COVID-19 caused by aggravating people’s anxiety.Keywords: Covid-19, public attitude, social media, cognition, affection, patriotism

Yanran Yang,1 Daiyun Chen,2 Yilin Li,1 Jinghua Zou,1 Ruiqi Han,1 Hongkun Li,1 Jun Zhang1 1Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Orthodontics, School of Stomatology, Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Jun Zhang, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cnPurpose: Puerarin (C21H20O10) is a phytoestrogen that possesses various pharmacological effect, and several researches have revealed the relationship between puerarin and bone metabolism. This study was aimed to evaluate the potential influence of puerarin on the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) as well as on new bone formation following rapid maxillary expansion (RME) model in rats.Methods: Rat BMSCs were adopted, and the cell proliferation was detected by cell-counting kit-8 (CCK-8) assay in vitro experiments. Alkaline phosphatase (ALP) activity and alizarin red staining were analyzed quantitatively to show extracellular matrix mineralization. The mRNA and protein expression levels were used to detect osteogenic differentiation of BMSCs. In vivo bone regeneration was analyzed in a rat RME model. Eighteen 6-week-old male Wistar rats were divided into 3 groups: group 1 without any treatment, group 2 received RME and saline solution (15mg/kg), group 3 received RME and puerarin solution (15mg/kg). After 2 weeks, micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) staining, and Masson staining were used to detect the new bone formation and morphological changes. Besides, ALP and bone morphogenetic protein 2 (BMP2) expression levels in mid-palatal suture were evaluated by immunohistochemical staining.Results: The results showed that puerarin upregulates cell proliferation dose-dependently. ALP activity and mineralized matrix generation were clearly enhanced at certain specific concentrations (10− 5 and 10− 6 mol/L); the expression levels of the osteoblast-related genes and proteins were increased. The measurement of micro-CT imaging revealed that puerarin significantly promoted new bone formation. Concomitantly, the histological examinations showed that puerarin solution enhanced osteogenesis in mid-palatal suture.Conclusion: Those works indicated that puerarin regulates osteogenesis in vitro and exerts a beneficial impact on bone regeneration in vivo, revealing that puerarin treatment may become one of the potential keys for improving the stability and preventing relapse of RME.Keywords: bone marrow-derived mesenchymal stem cells, bone regeneration, micro-CT, rapid maxillary expansion

Pulin Li,1,&ast; Xiaojuan Chen,2,&ast; Sijing Zhou,3,&ast; Xingyuan Xia,1 Enze Wang,1 Rui Han,1 Daxiong Zeng,4,5 Guanghe Fei,1 Ran Wang1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, Hefei Second People’s Hospital, Hefei, People’s Republic of China; 3Department of Occupational Medicine, Hefei Third Clinical College of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, Suzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghe Fei; Ran Wang, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China, Tel/Fax +86 -551-62922913, Email guanghefei@hotmail.com; wangran@ahmu.edu.cnIntroduction: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DEP domain-containing 1 B (DEPDC1B) is involved in the development of several cancers; however, its role in LUAD is unknown. Therefore, we aimed to determine the biological function and prognostic value of DEPDC1B in LUAD.Material and Methods: We analyzed the correlation between DEPDC1B expression and the clinical features of LUAD and lung squamous cell carcinoma (LUSC). Survival was evaluated by generating Kaplan–Meier curves, which were used to analyze the relationship between DEPDC1B expression and prognosis in LUAD and LUSC. DEPDC1B expression in tumor and normal tissues from patients with LUAD and LUSC was determined using immunohistochemistry, and its clinical significance was analyzed. Finally, the correlation between the expression and biological function of DEPDC1B in LUAD was examined.Results: Our findings revealed that DEPDC1B expression was higher in tumor tissues than that in normal tissues from patients with LUAD and LUSC (P < 0.001). These results were confirmed in clinical samples from patients using immunohistochemistry. Analysis of a dataset from The Cancer Genome Atlas (TCGA) showed that high DEPDC1B expression was associated with poor prognosis only in patients with LUAD (P < 0.001). Similarly, high DEPDC1B expression was related to shorter overall survival (OS) and progression-free interval (PFI) in patients with LUAD. These associations were not observed in LUSC. Functional enrichment analysis suggested that DEPDC1B promoted tumor development in LUAD by regulating the cell cycle.Conclusion: High DEPDC1B expression predicts poor prognosis in patients with LUAD. Thus, DEPDC1B has potential as a therapeutic target for LUAD.Graphical Abstract: Keywords: DEP domain-containing 1B, lung adenocarcinoma, prognosis, immunohistochemistry, bioinformatics

Rongfeng Han, Yang Zhang, Xia Jiang Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Rongfeng Han, Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of China, Email hanmenghappy@126.comAim: The aim of this study was to investigate the association between serum uric acid (SUA) levels and four insulin resistance surrogates in patients with type 2 diabetes (T2DM). The four non-insulin-based indexes of insulin resistance (IR) include the glucose and triglycerides index (TyG), TyG index with body mass index (TyG-BMI), ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-c) and metabolic score for insulin resistance (METS-IR).Methods: A total of 687 patients with T2DM were enrolled in the current study. Patients were stratified into three groups according to their levels of SUA. Spearman correlation was used to analyze the correlation between SUA and clinical variables. Multiple linear regression analysis was used to assess the association between SUA and the four insulin resistance surrogates. Receiver operating characteristic (ROC) analyses and the area under the ROC curve (AUC) were then used to assess the ability of TyG, TyG-BMI, TG/HDL-c, and METS-IR to discriminate hyperuricemia (HUA) in T2DM.Results: SUA in T2DM was significantly positively correlated with TyG (r 0.406 P < 0.01), TyG-BMI (r 0.272 P < 0.01), TG/HDL-c (r 0.493 P < 0.01), and METS-IR (r 0.238 P < 0.01). Furthermore, higher values of the four insulin resistance surrogates were independently correlated with higher SUA levels in T2DM patients (P < 0.01 for all) after adjusting for confounding factors. TyG, TyG-BMI, TG/HDL-c, and METS-IR all had a significant discriminative ability for HUA in patients with T2DM. The AUC values were 0.693 (95% CI 0.645– 0.741), 0.649 (95% CI 0.599– 0.699), 0.768 (95% CI 0.726– 0.811), and 0.660 (95% CI 0.609– 0.710), respectively.Conclusion: The present study suggests that TyG, TyG-BMI, TG/HDL-c and METS-IR had a significant correlation with SUA in T2DM. TG/HDL-c was the best marker among the four insulin resistance surrogates for the identification of HUA in T2DM.Keywords: type 2 diabetes, serum uric acid, insulin resistance, TyG, TyG-BMI, TG/HDL-c, METS-IR

Fei Guo,1,&ast; Ruili Han,1,&ast; Ting Luo,2,&ast; Shengyang Jin,3 Yuting Yan,1 Jun Wang,4 Xude Sun,1 Changjun Gao1 1Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Anesthesiology, Shaanxi Provincial Armed Police Hospital, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjun Gao; Xude Sun, Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, People’s Republic of China, Tel +86-13379227869 ; +86-13891905550, Fax +86-029-84777439, Email gaocj74@163.com; sunxude@fmmu.edu.cnPurpose: This study aims to evaluate the psychological status and the attitudes toward the novel coronavirus disease 2019 (COVID-19) vaccine among anesthesiologists. We expected to analyze related factors and offer them some strategies to prevent and manage psychological issues under the post COVID-19 era.Methods: Based on the Checklist for Reporting Results of Internet E-Surveys (CHERRIES), an online survey was designed and conducted among anesthesiologists in Shaanxi, China. Participants were asked to complete a validated questionnaire voluntarily. The following tests were performed: Depression, Anxiety and Stress Scale (DASS-21), Primary Care Post-traumatic Stress Disorder Screen (PC-PTSD), and the attitudes toward COVID-19 vaccine.Results: A total of 795 anesthesiologists completed the survey, the majority of them were female, young and middle-aged, well educated, and married. The prevalence of depression, anxiety, and stress in this sample were 26.5%, 35.5%, and 19.9%, respectively. Longer daily working time, concomitant basic chronic disease, and COVID-19 exposure were extracted as risk factors for the psychological symptoms, while vaccination, elder age, and married status were negatively associated with them. An unsatisfied vaccination rate (71.9%) which might be linked with inadequate awareness and perception of the COVID-19 vaccine was also detected in this study.Conclusion: Anesthesiologists are still under rising pressure of psychological symptoms in the post COVID-19 era. It is imperative to afford continuous psychological support to them and ensure their mental health and professional performance.Keywords: COVID-19, anesthesiologist, depression, anxiety, stress

Yajing Fu,1 Dan Ma,2 Fengyan Fan,3 Tongke Sun,1 Ruiqi Han,1 Yanran Yang,1 Jun Zhang1 1Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Orthodontics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Orthodontics, Hangzhou Stomatological Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, People’s Republic of China, Tel +86 139 5310 9816, Email zhangj@sdu.edu.cnPurpose: Stem cells from the apical papilla (SCAPs) are promising seed cells for tissue regeneration medicine and possess the osteogenic differentiation potential. Wnt5a, a typical ligand of the noncanonical Wnt pathway, exhibits diverse roles in the regulation of osteogenesis. The transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1) is a core regulator in the Hippo pathway and regulates stem behavior including osteogenic differentiation. This study aims to examine how Wnt5a regulates SCAPs osteogenesis and explore the precise mechanistic relationship between Wnt5a and TAZ.Methods: SCAPs were isolated from developing apical papilla tissue of extracted human immature third molars in vitro. ALP staining, ALP activity and Alizarin red staining were used to evaluate osteogenic capacity. Osteogenic-related factors were assessed by qRT-PCR or Western blotting. Additionally, the receptor tyrosine kinase-like orphan receptor 2 (ROR2) was detected by immunocytofluorescence staining and silenced by small interfering RNA to verify the function of Wnt5a/ROR2 in TAZ-mediated osteogenesis. And we constructed TAZ-overexpression and β-catenin-overexpression SCAPs generated by lentivirus to explore the precise mechanistic relationship between Wnt5a and TAZ.Results: Wnt5a (100ng/mL) significantly suppressed ALP activity, mineralization nodules formation, expression of osteogenic-related factors. Meanwhile, it decreased the expression of TAZ mRNA and protein. TAZ overexpression promoted osteogenesis of SCAPs while Wnt5a could block TAZ-mediated osteogenesis. Furthermore, ROR2 siRNA (siROR2) was found to upregulate TAZ and canonical Wnt pathway signaling related molecules such as β-catenin, GSK3β and p-GSK3β. The suppression of Wnt5a/ROR2 on osteogenesis was significantly reversed by β-catenin overexpression through Wnt5a/ROR2/β-catenin/TAZ pathway.Conclusion: Taken together, the present study demonstrates that Wnt5a suppresses TAZ-mediated osteogenesis of SCAPs and there may be a Wnt5a/ROR2/β-catenin/TAZ pathway regulating osteogenesis of SCAPs. Moreover, Wnt5a could be a candidate for regulators in tissue regeneration.Graphical Abstarct: Keywords: Wnt5a, TAZ, stem cells from the apical papilla, osteogenesis, β-catenin

Binbin Zhang,1,&ast; Aiqun Xu,2,&ast; Dong Wu,1,&ast; Wanli Xia,3,&ast; Pulin Li,1 Enze Wang,1 Rui Han,1 Peng Sun,1 Sijing Zhou,4,5 Ran Wang1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of General Medicine, Hefei Second People’s Hospital, Hefei, Anhui Province, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 4Hefei Third Clinical College of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sijing ZhouHefei Prevention and Treatment Center for Occupational Diseases, Hefei, 230022, People’s Republic of ChinaTel/Fax +86 551-63672040Email zhousijing@yeah.netRan WangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Tel/Fax +86-551-6292-2914Email ranwangtjmu@hotmail.comPurpose: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The mechanisms underlying NSCLC initiation and progression require further investigation. The purpose of this study was to investigate the role of ADP ribosylation factor-like GTPase 14 (ARL14) related to the progression of NSCLC.Patients and Methods: We analyzed the correlation between clinical characteristics and ARL14 expression using data from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis was conducted to evaluate the prognostic value of ARL14 in NSCLC. Functions of ARL14 were identified by enrichment analysis. The relationship between ARL14 expression and immune cell infiltration was also studied. Furthermore, ARL14 expression was examined using immunohistochemistry, and its clinical significance was analyzed in 120 patients with NSCLC.Results: Our study revealed that the expression level of ARL14 in patients with NSCLC was higher than that in normal tissues. Using TCGA data, higher ARL14 expression in lung adenocarcinoma was associated with residual tumor (P = 0.017), while it was associated with age (P = 0.003) and N stage (P = 0.009) in lung squamous cell carcinoma. Similar results were obtained from 120 patients with NSCLC. High ARL14 expression was associated with poor overall survival and progression-free survival in NSCLC. Multivariate analysis revealed that ARL14 was an independent risk factor for patients with NSCLC. Functional enrichment analysis indicated that ARL14 was related to the occurrence and development of tumors.Conclusion: Increased ARL14 expression was considerably correlated with poor survival in NSCLC, and it might be a promising prognostic biomarker for NSCLC.Keywords: ADP ribosylation factor-like GTPase 14, non-small cell lung cancer, prognosis, immunohistochemistry, bioinformatics

Yue Sun,1,2 Renru Han,1,2 Li Ding,1,2 Yang Yang,1,2 Yan Guo,1,2 Shi Wu,1,2 Fupin Hu,1,2 Dandan Yin1,2 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of ChinaCorrespondence: Fupin Hu; Dandan Yin Tel/Fax +86 21 52888186; +86 21 52888196Email hufupin@fudan.edu.cn; yindandan@fudan.edu.cnPurpose: OXA-10-type class D β-lactamases have shown their evolutionary potential of enhancing carbapenem resistance. This study aimed to elucidate the role of OXA-10 variants in clinical isolated multidrug resistant (MDR) Pseudomonas aeruginosa and characterize the first appearance of OXA-677 in China.Methods: Six blaOXA-10-like-positive strains were screened by PCR from 41 P. aeruginosa strains, which were resistant to both carbapenems and ceftazidime-avibactam, collected across China in 2018. The minimum inhibitory concentrations (MIC) were determined with the broth microdilution method. The resistance-associated genes and genetic environment were investigated by whole-genome sequencing (WGS). The function and mechanism of OXA-677 β-lactamase were identified by molecular cloning and protein structure modeling.Results: All the blaOXA-10-like-positive Pseudomonas aeruginosa were MDR strains. They also had outer membrane porin defects and produced β-lactam resistance gene blaPER-1, fluoroquinolone-resistant gene crpP, aminoglycoside-resistance gene aph(3ʹ)-IIb, aph(6)-Id, aacA and aadA, fosfomycin-resistance gene fosA, sulfamethoxazole-resistance gene sul1, and chloramphenicol-resistance gene catB7. All blaOXA-10 variants were located in a Tn1403-related transposon, containing aacA4-12-blaOXA-677-aadA1, aacA4-12-blaOXA-101-aadA5, and blaOXA-246-aacA3-aadA13 gene cassette arrays, respectively. Notably, the blaOXA-677 producer showed a high MIC level of meropenem (MIC> 64 mg/L). Compared to blaOXA-10, blaOXA-677 was found a G-to-T transversion at position 350, leading to a phenylalanine-for-valine substitution in position 117, which is closer to leucine155 in the omega loop of the active site. MIC of meropenem for E. coli DH5α with the recombinant plasmid pHSG398 carrying blaOXA-677 was elevated by 8 times.Conclusion: We speculate that the OXA-10-like enzymes and the decrease of membrane permeability confer carbapenem resistance, and the V117 substitution in OXA-677 might lead to a higher resistance level of meropenem.Keywords: Pseudomonas aeruginosa, blaOXA-677, blaOXA-10-like gene, CHDL

Zhen Wang,&ast; Huilin Yan,&ast; Dingcai Cheng, Lei Xu, Tianming Shen, Yi Chen, Rongbo Han, Yanshi Xue Department of Urology, Taixing People’s Hospital, Taixing City, 225400, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanshi Xue; Rongbo HanDepartment of Urology, Taixing People’s Hospital, No. 1 Changzheng Road, Taixing City, 225400, Jiangsu Province, People’s Republic of ChinaTel +86 523-87656001Email yanshi_xue@163.com; hanrongbo1020@163.comBackground: LncRNA plays a vital role in tumorigenesis and development. This study aimed to explore the novel lncRNA affecting bladder cancer progression.Methods: The open-access data of bladder cancer patients, including transcriptome profiles and corresponding clinical information were all obtained from The Cancer Genome Atlas database. All the statistical analysis were performed using R software, SPSS and GraphPad Prism 8. CCK8, colony formation, apoptosis detection and tumorigenicity assay were used to assess cell proliferation ability. Transwell assay and wound-healing assay were used to evaluate cell metastasis potential.Results: Our result showed that the lncRNA LINC01614 was highly expressed in bladder cancer tissue and cell lines. Meanwhile, patients with high LINC01614 expression level tend to have poor clinical features and shorter survival time. Further experiments demonstrated that the inhibition of LINC01614 could significantly hamper the proliferation and invasion of bladder cancer cells. Then, we found that the LINC01614 could regulate RUNX2 expression through miR-137. GSEA analysis indicated that the Wnt/β-catenin signaling pathway might be the downstream pathway of LINC01614. Further experiments showed that the LINC01614 act as an oncogene in bladder cancer partly depending on the RUNX2/Wnt/β-catenin axis, making it an underlying therapeutic target.Conclusion: In all, LINC01614 facilitates bladder cancer cells proliferation, migration and invasion through the miR-217/RUNX2/Wnt/β-catenin axis.Keywords: LINC01614, bladder cancer, lncRNA, Wnt/β-catenin

Leilei Wang,1,2 Yuancheng Chen,1– 3 Renru Han,1,2 Zhiwei Huang,1– 3 Xuefei Zhang,1,2 Fupin Hu,1,2 Fan Yang1,2 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of China; 3Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Fan Yang; Fupin HuInstitute of Antibiotics, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai, 200040, People’s Republic of ChinaTel +86 21 52888193Email fanyang9@fudan.edu.cn; hufupin@fudan.edu.cnPurpose: To evaluate in vitro activities of β-lactam antibiotics alone and in combination with sulbactam at different ratios against Acinetobacter baumannii clinical strains from China.Methods: A total of 300 clinical isolates of A. baumannii were collected from 29 hospitals across China in 2018. Susceptibility to common antibiotics was assessed, and β-lactamase genes were detected. In vitro activity of ampicillin, cefoperazone and imipenem was tested alone and in combination with sulbactam at the ratios of 2:1, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3.Results: High resistant rates for common antibiotics were observed except tigecycline and polymyxin B. Among carbapenem-resistant A. baumannii, 97.3% isolates harbored blaOXA-23. MIC50 and MIC90 values for sulbactam were 32 mg/L and 64 mg/L, respectively. High resistant rates for ampicillin, cefoperazone and imipenem were observed (92.3%, 93% and 85.3%, respectively). A stepwise increase in the ratio of sulbactam to partner β-lactam antibiotics led to a stepwise decrease in the MICs and a stepwise increase in the susceptible rates. The susceptible rates for imipenem-sulbactam 1:3, ampicillin-sulbactam 1:3 and cefoperazone-sulbactam 1:3 reached 16.3%, 58.3% and 91%, respectively.Conclusion: The increasing proportion of sulbactam could enhance antimicrobial activities of imipenem-sulbactam, ampicillin-sulbactam and cefoperazone-sulbactam combinations against A. baumannii clinical strains in China, with cefoperazone-sulbactam as the most potent compound.Keywords: sulbactam, ampicillin, cefoperazone, imipenem, Acinetobacter baumannii

Yubo Wang,1,* Rui Han,1,* Qiushi Wang,2 Jie Zheng,1 Caiyu Lin,1 Conghua Lu,1 Li Li,1 Hengyi Chen,1 Rongbing Jin,3 Yong He1 1Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong HeDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, 10# Changjiangzhilu Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel +86-2368757791Fax +86-2368700970Email heyong@tmmu.edu.cnRongbing JinDepartment of Nuclear Medicine, Daping Hospital, Army Medical University, 10# Changjiangzhilu Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel +86-2368757641Email jinrb99@126.comPurpose: To investigate the potential of maximum standardized uptake value (SUVmax) in predicting epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients.Methods: Clinical data of 311 NSCLC patients who had undergone both EGFR mutation test and 18F-FDG PET/CT scans between January 2013 and December 2017 at our hospital were retrospectively analyzed. Patients were sub-grouped by their origin of SUVmax. Univariate and multivariate analyses were performed to investigate the association between clinical factors and EGFR mutations. Receiver operating characteristic curve (ROC) analysis was performed to confirm the predictive value of clinical factors. In vitro experiments were performed to confirm the correlation between EGFR mutations and glycolysis.Results: EGFR-mutant patients had higher SUVmax than the wild-type patients in both primary tumors and metastases. In the multivariate analysis, SUVmax, gender and histopathologic type were determined as independent predictors of EGFR mutation status for patients whose SUVmax were obtained from the primary tumors; while for patients whose SUVmax were obtained from the metastases, SUVmax, smoking status and histopathologic type were regarded as independent predictors. ROC analysis showed that SUVmax of the primary tumors (cut off > 10.92), not of the metastases, has better predictive value than other clinical factors in predicting EGFR mutation status. The predict performance was improved after combined SUVmax with other independent predictors. In addition, our in vitro experiments demonstrated that lung cancer cells with EGFR mutations have higher aerobic glycolysis level than wild-type cells.Conclusion: SUVmax of the primary tumors has the potential to serve as a biomarker to predict EGFR mutation status in NSCLC patients.Keywords: non-small cell lung cancer, epidermal growth factor receptor, SUVmax, receiver operating characteristic curve

Wen-Chao Ji,1 Guang-Jian Bao,1 Fang-Wu Yang,2 Lei Sun,1 Rui Han1 1Department of Hepatobiliary Surgery, Zaozhuang Municipal Hospital, Zaozhuang, 277100 Shandong Province, People’s Republic of China; 2General Surgery Department, Zaozhuang Mining Group Central Hospital, Zaozhuang, 277100 Shandong Province, People’s Republic of ChinaCorrespondence: Rui HanDepartment of Hepatobiliary Surgery, Zaozhuang Municipal Hospital, NO. 41 Longtou Road, Shizhong District, Zaozhuang, 277100, Shandong Province, People’s Republic of ChinaTel + 86-18369221166Email hanruihenry@126.comObjective: This research was designed to probe into the expression and related mechanism of lncRNA NR2F1-AS1 and H19 in hepatocellular carcinoma (HCC).Methods: Forty-two HCC patients who came to our hospital from February 2018 to August 2019 were included into a research group (RG). Meanwhile, 46 healthy controls were regarded as a control group (CG). BEL-7402, Huh-7 human hepatoma cells and HL-7702 human normal liver cells were purchased, and the NR2F1-AS1 and H19 levels in serum and tissues of HCC patients were detected. PcDNA3.1-NR2F1-AS1, si-NR2F1-AS1, NC, pcDNA3.1-H19 and si-H19 were transfected into BEL-7402 and Huh-7 cells. The NR2F1-AS1 and H19 levels in samples were detected via qRT-PCR, and the expression of apoptosis-related proteins in cells was tested through WB. Cell proliferation, invasion, or apoptosis was detected by CCK8, Transwell or flow cytometry, respectively.Results: The NR2F1-AS1 and H19 levels were high in human hepatoma cells, and AUCs of lncRNA NR2F1-AS1 and lncRNA H19 were both > 0.8. The lncRNA NR2F1-AS1 and lncRNA H19 were associated with HCC staging. After transfection of pcDNA3.1-NR2F1-AS1, si-NR2F1-AS1, NC, pcDNA3.1-H19, si-H19 BEL-7402 and Huh-7 cells, silencing NR2F1-AS1 and H19 expression can promote apoptosis and inhibit cell growth, while silencing their over-expression can inhibit the EMT process of Huh-7 cells.Conclusion: lncRNA NR2F1-AS1 and lncRNA H19 genes are abnormally expressed in HCC. Furthermore, the two can suppress the EMT process of Huh-7 cells and promote apoptosis effectively.Keywords: lncRNA H19, lncRNA NR2F1-AS1, hepatocellular carcinoma, HCC, trophoblast cells, invasion, apoptosis

Mingjia Peng,1,2 Renru Han,1,2 Yan Guo,1,2 Yonggui Zheng,1,2 Feifei Yang,1,2 Xiaogang Xu,1,2 Fupin Hu1,2 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of China; 3National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Fupin Hu; Xiaogang Xu Email hufupin@fudan.edu.cn; xuxiaogang@fudan.edu.cnBackground: The spread of KPC-producing Enterobacteriaceae has triggered a global public health concern, with KPC-2-positive strains being the most prevalent in China. We hereby studied the in vitro combined inhibitory activities of three kinds of β-lactam antibiotics and clavulanic acid at different concentrations against blaKPC-2-positive Klebsiella pneumoniae to explore the antimicrobial characteristics of these combinations and alternative therapeutic regimens for infections caused by blaKPC-2-positive K. pneumoniae strains.Materials and Methods: In this study, 153 clinically isolated blaKPC-2-positive K. pneumoniae strains from 19 provinces in China were collected from 2016 to 2018. Antimicrobial susceptibility testing of imipenem/clavulanic acid, meropenem/clavulanic acid, ceftazidime/clavulanic acid, and each antimicrobial agent alone was performed by broth microdilution technique according to the CLSI guidelines. The concentration ratios of β-lactam antibiotics to clavulanic acid were as follows: 1:1, 1:2, 1:4, 1:8, 1:16, 1:32. The antimicrobial susceptibility of the combinations was determined according to the breakpoints of Imipenem, meropenem, and ceftazidime established by the CLSI directives for Enterobacteriaceae.Results: The MICs of all three combinations gradually declined with increments in the proportion of clavulanic acid in the regimens, and the most significant decline in the MIC50 and MIC90 was seen in combinations at the concentration ratio of 1:1 (also 1:2 for meropenem/clavulanic acid). When the concentration of clavulanic acid was restricted to 4 mg/L, the susceptibility of more than 70% of the isolates to the regimens could be restored with imipenem MIC 2– 4 mg/L, meropenem MIC 2– 8 mg/L or ceftazidime MIC 8mg/L. However, the percentage decreased to 30 to 40% when the initial MIC level was higher.Conclusion: The highest combined inhibitory activity of β-lactam antibiotics/clavulanic acid at low concentration ratios against blaKPC-2-positive K. pneumoniae may offer a new way to optimize the effects of these antimicrobial regimens.Keywords: KPC, Enterobacteriaceae, combined inhibitory activity, clavulanic acid, β-lactam antibiotic

Jin Man,1 Jiajia Dong,2 Yilin Wang,1 Leiliang He,1 Songcheng Yu,1 Fei Yu,1 Jia Wang,1 Yongmei Tian,1 Lie Liu,1 Runping Han,2 Hongchao Guo,1 Yongjun Wu,1,3 Lingbo Qu2,4 1College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, People’s Republic of China; 2College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, People’s Republic of China; 3The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou, Henan 450001, People’s Republic of China; 4Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou, Henan 450001, People’s Republic of ChinaCorrespondence: Yongjun WuCollege of Public Health, Zhengzhou University, No.100 Science Avenue, Zhengzhou City 450001, People’s Republic of ChinaTel/Fax +86-371-67781450Email wuyongjun135@126.comLingbo QuCollege of Chemistry, Zhengzhou University, No. 100 Science Avenue, Zhengzhou City 450001, People’s Republic of ChinaTel/Fax +86-371-67781450Email qulingbo@zzu.edu.cnBackground: As two important tumor markers, vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) have a great value for clinical application in the early diagnosis of cancer. Due to the complex composition of biological samples, the results from combined detection of CEA and VEGF are often taken as a comprehensive indicator in order to make an accurate judgment on a disease. However, most of the current methods can only be used to detect the content of one biomarker. Therefore, it is necessary to explore a simple, rapid, low-cost, and highly sensitive method for the simultaneous detection of CEA and VEGF.Methods: Based on specific aptamers and magnetic separation, a time-resolved chemiluminescence enzyme-linked aptamer assay was developed for the simultaneous detections of CEA and VEGF in serum samples.Results: Under the optimal conditions, the linear range of the calibration curve for VEGF was from 0.5 to 80 ng mL− 1, and the limit of detection was 0.1 ng mL− 1. The linear range of the calibration curve for CEA was 0.5 to 160 ng mL− 1, and the limit of detection was 0.1 ng mL− 1. The established method was applied to detect VEGF and CEA in serum samples. The results were consistent with those of commercial kits.Conclusion: The method has high sensitivity and can quickly obtain accurate results, which could greatly improve the measurement efficiency, reduce the cost, and also reduce the volume of sample consumed. It can be seen that the method established in this study has important application value and broad application prospect in clinical diagnosis.Keywords: chemiluminescence assay, simultaneous detection, vascular endothelial growth factor, time-resolved, carcinoembryonic antigen

Qingyu Shi,1,2 Renru Han,1,2 Yan Guo,1,2 Yonggui Zheng,1,2 Yang Yang,1,2 Dandan Yin,1,2 Rong Zhang,3 Fupin Hu1,2 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Fupin Hu Email hufupin@fudan.edu.cnBackground: RmtF, as 16S rRNA methyltransferase, leads to high-level resistance to aminoglycoside and is now barely reported.Methods and Results: Three rmtF-positive Klebsiella pneumoniae isolates, belonging to the pandemic clone sequence type 15, were isolated from children and coproduced blaOXA-232 and blaCTX-M-15. The rmtF gene was located on an IncFIB transformable plasmid of 128,536-bp and blaOXA-232 was on a 6141-bp ColKP3 plasmid, respectively.Conclusion: Plasmids with rmtF found worldwide, shared relatively low similarity, and merely matched partly in their multidrug resistance region. Notably, clinical isolates coproducing rmtF and blaOXA-232 are gradually increasing in China.Keywords: Klebsiella pneumoniae, RmtF, blaOXA-232, ST15, aminoglycoside

Yuzhu Dong,1,* Ying Li,2,* Ying Zhang,1 Dan Sun,1 Qian Du,1 Tao Zhang,1 Mengmeng Teng,1 Ruiying Han,1 Yan Wang,3 Li Zhu,4 Jin’e Lei,5 Yalin Dong,1 Taotao Wang1 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 2Department of Pharmacy, Xi’an NO.3 Hospital, Xi’an 710082, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 4Department of Infections, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 5Department of Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yalin DongDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaTel/Fax +86-29-85323240Email dongyalin@mail.xjtu.edu.cnTaotao WangDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaTel/Fax +86-29-85323243Email wangtaotao1989@mail.xjtu.edu.cnBackground: Gram-negative bacteria bloodstream infection (GNB-BSI) results in considerable mortality and hospitality costs in cirrhotic patients. β-lactam/β-lactamase inhibitor combinations (BLBLIs) and carbapenems (CARs) are widely recommended for treating GNB-BSI in cirrhotic patients, while the efficacy and cost-effectiveness of two strategies have never been evaluated. Therefore, we conducted a retrospective cohort study to evaluate the efficacy and the cost-effectiveness of BLBLIs and CARs.Patients and Methods: Cirrhotic patients with GNB-BSI treated by BLBLIs or CARs were included. A propensity score-matching analysis was performed to compare the efficacy between BLBLIs and CARs. A decision tree was used to estimate the clinical outcomes and direct costs of treating BSI using two strategies from the patients’ perspective.Results: No statistically significant difference was found between the BLBLIs (n = 41) group and the CARs (n = 43) group regarding the time to defervescence (2.4 ± 0.2 vs 2.5 ± 0.3, P = 0.94). Thirty-seven patients from each group were matched in propensity-score-matched cohort, and there was no significant difference between two groups in terms of the time to defervescence (2.4 ± 0.3 vs 2.4 ± 0.3, P = 0.75) and success rate (86.5% vs 78.4%; OR = 0.57; P = 0.36). Based on the drug and hospital costs in China, cefoperazone/sulbactam was cost-effective in the present analysis under the willingness-to-pay threshold (¥ 64,644).Conclusion: The efficacy of BLBLIs is similar to CARs. Cefoperazone/sulbactam could be a cost-effective therapy in cirrhotic patients with GNB-BSI. Carbapenems-sparing regimens should be encouraged in regions with a low prevalence of MDR bacteria.Keywords: liver cirrhosis, gram-negative bacteria, bloodstream infection, efficacy, cost-effectiveness

Qingbin Wu,1,* Xiaochen Yuan,1,* Bingwei Li,1,* Ruiqin Han,2 Honggang Zhang,1 Ruijuan Xiu1 1Institute of Microcirculation, Chinese Academy Medical Sciences & Pecking Union Medical College; 2Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaochen Yuan; Honggang ZhangInstitute of Microcirculation, Chinese Academy Medical Sciences & Pecking Union Medical College, 5, Dong Dan San Tiao, Beijing 100005, People’s Republic of ChinaTel +0086-10-65126407Fax +0086-10-65251957Email yuanxc@imc.pumc.edu.cn; zhanghg1966126@163.comObjective: To investigate the effect of salvianolic acid A (SA) on the permeability of blood–brain barrier (BBB) and brain microvascular pericyte apoptosis in spontaneously hypertensive rats (SHR).Methods: Evans Blue was used to determine the BBB permeability in control rats and SHR. Western blotting was used to evaluate the expression levels of relevant proteins in the pericytes isolated from the differentially treated animals. An in vitro model of hypertension was established by stimulating pericytes with angiopoietin-2 (Ang2). MTT assay was used to assess cell viability, and apoptosis and cell cycle distribution were analyzed by flow cytometry.Results: SA attenuated BBB permeability in SHR in a dose-dependent manner. It downregulated pro-apoptotic proteins including p53, p21, Fas, FasL, cleaved-caspase 3/caspase 3 and Bax in the pericytes of SHR and upregulated CDK6, cyclin D1, CDK2, cyclin E and Bcl2. In addition, SA activated the Ras/Raf/MEK/ERK pathway in a dose-dependent manner by increasing the levels of Ras, Raf, p-MEK1, p-MEK2, p-ERK1 and p-ERK2. Finally, SA reduced Ang2-induced apoptosis of cerebral microvessels pericytes and decreased the proportion of cells in the G0/G1 phase of the cell cycle by inhibiting the p53 pathway and activating the Ras/Raf/MEK/ERK pathway.Conclusion: SA reduced BBB permeability in spontaneously hypertensive rats, possibly by inhibiting Ang2-induced apoptosis of pericytes by activating the Ras/Raf/MEK/ERK pathway.Keywords: salvianolic acid A, blood–brain barrier, hypertension, pericytes, apoptosis

Wang Z, Yan H, Cheng D, et al. Cancer Manag Res. 2021;13:8387–8397. At the authors request, the Editor and Publisher of Cancer Management and Research wish to retract the published article. The authors have informed the journal that they have concerns regarding the reliability of the published results. In addition, they are unable to provide adequate original data for their study. The authors requested to retract the article and the Editor has agreed with this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Jing Tian,1 Jingjing Yan,2 Qing Zhang,1 Hong Yang,2 Xinlong Chen,1 Qiang Han,2 Rui Han,1 Jia Ren,1 Yanbo Zhang,2,3 Qinghua Han1 1Department of Cardiology, The 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province 030001, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province 030001, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi Province 030001, People’s Republic of ChinaCorrespondence: Qinghua HanDepartment of Cardiology, The 1st Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, Shanxi Province 030001, People’s Republic of ChinaTel +86 3100113031Fax +86 351 4867146Email syhqn@sohu.com Yanbo ZhangDepartment of Health Statistics, School of Public Health, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Shanxi Medical University, 56 South XinJian Road, Taiyuan, Shanxi Province 030001, People’s Republic of ChinaTel/fax +86 3543985051Email sxmuzyb@126.comBackground: The re-hospitalization rate of patients with heart failure remains at a high level, and studies of the subject have focused mainly on event-time outcomes. In addition to using re-hospitalization data with the outcomes of the event-time-count, this study introduces the conditional frailty model, which could help obtain more reasonable results.Materials and methods: This prospective observational cohort study enrolled 1484 patients with heart failure caused by coronary heart disease. The outcomes of heart failure readmissions and the case report form data were collected. Based on the traditional Cox model with event-time outcomes, the mixed effects of a conditional frailty model were added to analyze the event-time-count longitudinal data.Results: The Cox regression model showed that non-manual work, diastolic dysfunction, and better medical compensation increased the risk of heart failure readmission, whereas treatment with beta-blockers decreased the risk. The conditional frailty model further revealed that age, female sex, non-manual work, better medical compensation, longer QRS duration, and treatment with percutaneous coronary intervention increased the risk of heart failure readmission.Conclusion: This study obtained more reliable, reasonable results based on longitudinal data and a mixed model. The results could provide more clinical epidemiological evidence for the management of heart failure.Keywords: heart failure, coronary heart disease, re-hospitalization, conditional frailty model

Rui Han,1,2 Xinyi Chen,1 Ya Li,1,2 Shunjia Zhang,2 Ruibai Li,1 Lingeng Lu3,41Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700 People’s Republic of China; 2Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA; 3Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, 06520-8034, USA; 4Center for Biomedical Data Science, Yale Cancer Center, Yale University, New Haven, CT, USABackground: Accumulating evidence suggests an antineoplastic role of MicroRNA-34a (miR-34a) in human cancer. However, its precise biological functions stay largely elusive.Purpose: Our study was aimed to investigate the impact of miR-34a on hepatocellular carcinoma (HCC) and its underlying apoptosis related mechanisms in vitro, as well as the association of miR-34a, E2F1 and E2F3 expression with patient survival of HCC using publicly accessed datasets.Methods: The HBV-expressing Hep3B and SNU-449 cell lines with or without enforced expression of miR-34a were in vitro cultured for cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation. Quantitative reverse transcription PCR (RT-qPCR) was performed for E2F1, E2F3 expression. Caspase-3 (CASP3) activity was determined using a CaspACETM, Assay System. Kaplan–Meier survival curves were used to analyze the associations of miR-34a, E2F1 and E2F3 expression and overall survival in HCC. Meta-analysis was performed to examine the differential expression of E2F1 and E2F3 between primary HCC vs normal tissues.Results: The results in vitro showed that enforced miR-34a expression significantly inhibited cell proliferation, migration, and invasion of both Hep3B and SNU-449. RT-qPCR results demonstrated that miR-34a could significantly suppress E2F1 and E2F3 expression, particularly in SNU-449. CASP3 activity in both Hep3B and SNU-449 increased in miR-34a treatment group. Overexpressed E2F1 and E2F3 were observed in primary HCC vs normal tissues. Survival analyses showed that HCC patients with either high miR-34a, or low E2F1, or low E2F3 expression had better survival than their opposite counterparts, respectively.Conclusion: Our study suggested thatmiR-34a can modulate the expression of E2F1, E2F3, and CASP3 activity, thereby repressing tumor aggressiveness and expediting apoptosis in liver cancer cellsKeywords: hepatocellular carcinoma, microRNA-34a, E2Fs, Caspase-3, prognosis

Jingsun Wei,* Yiqi Xue,* Xinying Huo, Rongbo Han, Xinyu Su, Yan Jin, Wenjing Zhao, Yuetong Chen, Honghong Zhang, Jiali Dai, Jinfei Chen Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Purpose: Gastric hepatoid adenocarcinoma is a rare subtype of primary gastric cancer and is a high-grade form of malignancy. However, the pathogenesis and molecular biology of gastric hepatoid adenocarcinoma remain poorly understood. The aim of this study was to establish and characterize a new human gastric hepatoid adenocarcinoma cell line, GC-030-35.Materials and methods: The GC-030-35 cell line was established from tumor cells from a 58-year-old Chinese man with gastric hepatoid adenocarcinoma. The cultured cells underwent immunocytochemistry and flow cytometry to confirm the tumor cell phenotype. RNA sequencing was performed to analyze the differences in gene expression between GC-030-35 cells compared with normal gastric epithelial cells. A zebrafish assay was performed. Gene enrichment analysis and interrogation of the bioinformatics databases, the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, were used for pathway analysis.Results: Flow cytometry analysis of the GC-030-35 cells showed a positive expression rate for CD44+ of 10.7%, high cell clonality, an average plating efficiency of 32%, cell-doubling time of 29.2 hours, and cell proliferation for >15 generations in serial culture. The zebrafish assay showed the ability of the GC-030-35 cells to proliferate, promote angiogenesis, and metastasize. RNA sequencing identified the functional clustering of 6,601 differentially expressed genes of GC-030-35, which were significantly different when compared with nonneoplastic gastric epithelial cells. Pathway enrichment analysis and interrogation of the GO and KEGG bioinformatics databases identified genes for microbial metabolism in diverse environments (63 genes), metabolism of xenobiotics by cytochrome P450 (CYP450; 25 genes), and the drug metabolism cytochrome P450 (28 genes).Conclusion: A human gastric hepatoid adenocarcinoma cell line, GC-030-35, was developed and characterized by comparison with normal gastric epithelial cells. Bioinformatics and gene analysis data showed that the CYP450 gene was significantly differentially expressed by GC-030-35 cells. Keywords: gastric hepatoid adenocarcinoma, cell line, differentially expressed genes, bioinformatics, carcinogenesis, cytochrome P450

Pengfei Zhang,1 Meng Zhang,1 Renfang Han,2 Kaiping Zhang,3 Huayang Ding,1 Chaozhao Liang,1 Li Zhang1 1Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, China; 2Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China; 3Department of Urology, Anhui Provincial Children’s Hospital, Hefei, China Background: Although miR-221/222 cluster plays an important role in many human malignancies, the correlation between miR-221/222 cluster overexpression and tumor prognosis remains controversial. Therefore, an updated meta-analysis was conducted to clarify its prognostic value in malignancy.Methods: We conducted a search of literature in English electronic databases of PubMed, Embase, and Cochrane Library, and Chinese electronic databases of China Biology Medicine disc and China National Knowledge Infrastructure to obtain appropriate studies. Besides, we extracted hazard ratios (HRs) and 95% CIs to evaluate the strength of the correlations. In addition, the results of different subgroups analyses and publication bias test were also shown in this article.Results: 32 publications, including 15 tumor types and 2,693 patients were embraced in this meta-analysis. The results of univariate (HR =1.69, 95% CI: 1.18–2.44, P

Rongbo Han,1–3 Jingsun Wei,1 Honghong Zhang,1 Xinyu Su,1 Xia Chu,4 Yuetong Chen,1 Yang Gong,1 Xiujuan Wang,2 Junfeng Shi,1 Jinfei Chen1,5 1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Oncology, Taixing People’s Hospital, Taixing, Jiangsu,People’s Republic of China; 3Clinical Research Center, Xuyi People’s Hospital, Xuyi, Jiangsu, People’s Republic of China; 4School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 5Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China Background: This study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC).Patients and methods: Samples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy. Results: TS (rs34743033) variant genotypes significantly prolonged the median overall survival (OS) time compared to the patients who only received adjuvant chemotherapy (HR 1.604, 95% CI 1.068–2.410, p=0.021). Moreover, 3R/3R variant genotypes were demonstrated to have a positive effect on the OS of patients who received chemotherapy based on cisplatin (HR 1.754, 95% CI 1.041–2.954, p=0.031) compared to oxaliplatin. A stratification analysis indicated that 2R/3R and 2R/2R variant genotypes were associated with inferior survival in GC patients with intestinal-type tumors, tumor less than 5 cm in size, and poorly differentiated tumors (p

Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.

In order to make benchmark validation of the nuclear data for gallium (Ga), tungsten (W) and beryllium (Be) in existing modern evaluated nuclear data files, neutron leakage spectra in the range from 0.8 to 15 MeV from slab samples were measured by time-of-flight technique with a BC501 scintillation detector. The measurements were performed at China Institute of Atomic Energy (CIAE) using a D-T neutron source. The thicknesses of the slabs were 0.5 to 2.5 mean free path for 14.8 MeV neutrons, and the measured angles were chosen to be 60∘ and 120∘. The measured spectra were compared with those calculated by the continuous energy Monte-Carlo transport code MCNP, using the data from the CENDL-3.1, ENDF/B-VII.1 and JENDL-4.0 nuclear data files, the comparison between the experimental and calculated results show that: The results from all three libraries significantly underestimate the cross section in energy range of 10–13 MeV for Ga; For W, the calculated spectra using data from CENDL-3.1 and JENDL-4.0 libraries show larger discrepancies with the measured ones, especially around 8.5–13.5 MeV; and for Be, all the libraries led to underestimation below 3 MeV at 120∘.