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Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Tao Chen,1– 3,&ast; Yumeng Wei,1– 3,&ast; Suyu Yin,1– 3,&ast; Wen Li,1– 3 Yuxiang Wang,1– 3 Chao Pi,1– 3 Mingtang Zeng,3,4 Xiaodong Wang,5 Ligang Chen,6 Furong Liu,7 Shaozhi Fu,8 Ling Zhao2,3 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; Luzhou, Sichuan, 646000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China, Tel +86 830 2681630, Email zhaoling@swmu.edu.cnPurpose: The present study aimed to develop a lipid nanoplatform, denoted as “BAL-PTX-LN”, co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs.Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining.Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration.Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications. Keywords: baicalin derivative, paclitaxel, chemotherapy, lung cancer, lipid nano platform, combination therapy

Sujin Yin,&ast; Jingen Dai,&ast; Lingling Lu Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingling Lu, Department of General surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, No. 26 of Daoqian Street, Suzhou District, Suzhou, 215000, People’s Republic of China, Tel +86 15262410849, Fax +86 51262362015, Email Lu_linglingyy@163.comObjective: To retrieve, evaluate, and summarise the clinical evidence for non-pharmacological interventions in adult postoperative delirium (POD), encompassing the preoperative, intraoperative, and postoperative phases.Methods: The methods included conducting searches on UpToDate Clinical Consultants, the Scottish Intercollegiate Guidelines Network, the National Institute for Health and Care Excellence, the Registered Nurses’ Association of Ontario, BMJ Best Practice, the Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, VIP, and the Chinese Biomedical Literature Service System. Clinical practice guidelines, clinical decision-making, evidence summaries, evidence synthesis, expert consensus, systematic reviews, and meta-analyses on non-pharmacological interventions for adult POD were examined, and the search period spanned between the establishment of each database and 30 October 2023.Results: A total of 17 documents were included, comprising three guidelines, one expert consensus, one clinical decision-making article, four evidence summaries, three systematic reviews, and five meta-analyses. These documents primarily focused on the following three aspects: preoperative, intraoperative, and postoperative care. In total, 30 “best evidence” instances were compiled.Conclusion: Considering the complexity and potential harm of adult POD, an accurate and timely evaluation of high-risk factors, alongside effective medical nursing strategies, is vital in its prevention and treatment. Non-pharmacological interventions remain the preferred choice for preventing and treating POD. Medical institutions should establish standardised processes for non-pharmacological intervention in adult POD, based on evidence-based medicine, to enhance the level of clinical care in this field.Keywords: adult postoperative delirium, non-pharmacological intervention, evidence-based nursing, perioperative care, evidence-based medicine

Ming Tang,1,2,&ast; Siyuan Wang,1,2,&ast; Yiwen Wang,1 Fanyi Zeng,1 Mianpeng Chen,1 Xindong Chang,1 Mingfei He,1 Qingqing Fang,1 Shiwu Yin1 1Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei City, Anhui Province, People’s Republic of China; 2The Fifth Clinical College of Medicine, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiwu Yin, Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, 574 Changjiang East Road, Yaohai District, Hefei City, Anhui Province, 230011, People’s Republic of China, Email yinshiwu@126.comPurpose: Previous studies highlight paraspinal muscles’ significance in spinal stability. This study aims to assess paraspinal muscle predictiveness for postoperative recurrent lumbar disc herniation (PRLDH) after lumbar disc herniation patients undergo percutaneous endoscopic transforaminal discectomy (PETD).Patients and Methods: Retrospectively collected data from 232 patients undergoing PETD treatment at our institution between January 2020 and January 2023, randomly allocated into training (60%) and validation (40%) groups. Utilizing Lasso regression and multivariable logistic regression, independent risk factors were identified in the training set to construct a Nomogram model. Internal validation employed Enhanced Bootstrap, with Area Under the ROC Curve (AUC) assessing accuracy. Calibration was evaluated through calibration curves and the Hosmer-Lemeshow goodness-of-fit test. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed for clinical utility analysis.Results: Diabetes, Modic changes, and ipsilesional multifidus muscle skeletal muscle index (SMI) were independent predictive factors for PRLDH following PETD (P< 0.05). Developed Nomogram model based on selected predictors, uploaded to a web page. AUC for training: 0.921 (95% CI 0.872– 0.970), validation: 0.900 (95% CI 0.828– 0.972), respectively. The Hosmer-Lemeshow test yielded χ2=5.638/6.259, P=0.688/0.618, and calibration curves exhibited good fit between observed and predicted values. DCA and CIC demonstrate clinical net benefit for both models at risk thresholds of 0.02– 1.00 and 0.02– 0.80.Conclusion: The Nomogram predictive model developed based on paraspinal muscle parameters in this study demonstrates excellent predictive capability and aids in personalized risk assessment for PRLDH following PETD.Keywords: lumbar disc herniation, percutaneous endoscopic transforaminal discectomy, postoperative recurrent lumbar disc herniation, predictive model

Abstract Background In a previously reported Phase I trial, we observed therapy‐associated declines in circulating myeloid‐derived suppressor cells (MDSCs) with the administration of white button mushroom (WBM) tablets in prostate cancer (PCa) patients. These observations led us to hypothesise that WBM could mitigate PCa progression by suppressing MDSCs. Methods We performed bidirectional translational research to examine the immunomodulatory effects of WBM consumption in both syngeneic murine PCa models and patients with PCa participating in an ongoing randomised Phase II trial (NCT04519879). Results In murine models, WBM treatment significantly suppressed tumour growth with a reduction in both the number and function of MDSCs, which in turn promoted antitumour immune responses mediated by T cells and natural killer (NK) cells. In patients, after consumption of WBM tablets for 3 months, we observed a decline in circulating polymorphonuclear MDSCs (PMN‐MDSCs), along with an increase in cytotoxic CD8+ T and NK cells. Furthermore, single immune cell profiling of peripheral blood from WBM‐treated patients showed suppressed STAT3/IRF1 and TGFβ signalling in circulating PMN‐MDSCs. Subclusters of PMN‐MDSCs presented transcriptional profiles associated with responsiveness to fungi, neutrophil chemotaxis, leukocyte aggregation, and regulation of inflammatory response. Finally, in mouse models of PCa, we found that WBM consumption enhanced the anticancer activity of anti‐PD‐1 antibodies, indicating that WBM may be used as an adjuvant therapy with immune checkpoint inhibitors. Conclusion Our results from PCa murine models and patients provide mechanistic insights into the immunomodulatory effects of WBM and provide a scientific foundation for WBM as a nutraceutical intervention to delay or prevent PCa progression. Highlights White button mushroom (WBM) treatment resulted in a reduction in pro‐tumoural MDSCs, notably polymorphonuclear MDSCs (PMN‐MDSCs), along with activation of anti‐tumoural T and NK cells. Human single immune cell gene expression profiling shed light on the molecular alterations induced by WBM, specifically on PMN‐MDSCs. A proof‐of‐concept study combining WBM with PD‐1 blockade in murine models revealed an additive effect on tumour regression and survival outcomes, highlighting the clinical relevance of WBM in cancer management.

Ming Tang,1,2,&ast; Siyuan Wang,1,&ast; Yiwen Wang,1 Mianpeng Chen,1 Xindong Chang,1 Mingfei He,1 Qingqing Fang,1 Shiwu Yin1 1Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei City, Anhui Province, People’s Republic of China; 2The Fifth Clinical College of Medicine, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiwu Yin, Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, 574 Changjiang East Road, Yaohai District, Hefei City, Anhui Province, 230011, People’s Republic of China, Email yinshiwu@126.comPurpose: To develop an individualized predictive model for postoperative recurrent lumbar disc herniation (PRLDH) in patients undergoing percutaneous endoscopic transforaminal discectomy (PETD) by considering postoperative activity factors.Patients and Methods: Retrospectively collected data from 612 LDH patients who underwent PETD in our institution from January 2017 to June 2023. They were divided into a training group (429 cases) and a validation group (183 cases). Lasso regression (Model 1) and random forest (Model 2) were applied for variable selection in the training group. The two models were compared in terms of discrimination (the area under curve, AUC), calibration (calibration curve), and clinical utility (decision curve analysis, DCA). Akaike information criterion (AIC) was used for model comparison, and internal validation employed 1000 times Bootstrap + 10-fold cross-validation. Finally, a Nomogram was constructed to display the results and uploaded to the web version.Results: Among 612 treated LDH patients, 66 (10.78%) developed PRLDH. Model 1, superior in AUC, calibration, DCA, and AIC over Model 2, was chosen as the predictive model. Logistic regression in the training group identified BMI, smoking, activity level score, time to first ambulation, diabetes, Modic change, and Pfirrmann grade as independent predictors of PRLDH. Model 1 exhibited a training group AUC of 0.813 (95% CI 0.753– 0.872) and a validation group AUC of 0.868 (95% CI 0.773– 0.962). At a Youden index of 0.50, sensitivity was 0.73, specificity was 0.77. Internal validation (1000 times Bootstrap + 10-fold cross-validation) for the training group showed accuracy of 0.889, kappa consistency of 0.112, and AUC of 0.757. The Hosmer-Lemeshow goodness-of-fit tests indicated good discriminative ability for Model 1 in both the training (χ2=2.895, P=0.941) and validation groups (χ2=8.197, P=0.414). The DCA and Nomogram are accessible at https://sofarnomogram.shinyapps.io/PRLDHNom/.Conclusion: The Nomogram predictive model, developed based on postoperative activity factors in this study, demonstrates excellent predictive capability, facilitating risk assessment for the occurrence of PRLDH after PETD.Keywords: Lumbar disc herniation, percutaneous endoscopic transforaminal discectomy, postoperative recurrent lumbar disc herniation, predictive model

Sheng Yin,1 YingRui Lin,1 Bingqi Wang,1 Yizhi Peng,2 Zeyou Wang,1 Xiaolin Zhu,1 Hao Liang,1 Xianping Li,1 Min Wang1 1Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410031, People’s Republic of ChinaCorrespondence: Min Wang, Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 13298697558, Email wangmin0000@csu.edu.cnPurpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy.Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR.Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P= 0.0182), PCT (P= 0.0029), and CRP (P= 0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P= 0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA< 7 was lower than that of the SOFA≥ 7 (P= 0.0334). ddPCR (OR: 1.789, P= 0.035) monitoring combined with PCT (OR: 1.787, P= 0.035) holded predictive value for SOFA progression (AUC=0.7913, P= 0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P= 0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P= 0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P= 0.0003).Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.Keywords: bloodstream infection, droplet digital polymerase chain reaction, interleukin-6, procalcitonin, prognosis

Liu J, Kang Y, Yin S, et al. Int J Nanomedicine. 2017;12:8085–8099. The authors have advised the control images for Figure 4A and B were the same to represent the one and the same control group. To alleviate any potential confusion this may have created, the authors have provided a corrected Figure 4. This correction does not change the scientific conclusions of the article in any way. Figure 4 Confocal microscopy investigation of the cellular distribution of lysosomes and zinc ions in SH-SY5Y cells after the two types of ZnO NP treatments.Abbreviation: NP, nanoparticle.Notes: After the SH-SY5Y cells were untreated (the Control group) or treated with the ZnOa NPs and ZnOb NPs (50 µg/mL) for 1 h, 3 h, or 5 h, the cells were loaded with FluoZin3 (green), LysoTracker (red) and Hoechst 33342 (blue). We observed almost no zinc ion fluorescence in the Control group, but significant zinc ions (green) were observed within 1 h after the ZnO NP treatment, and a slight increase in the zinc fluorescence (green) was observed in a time-dependent manner. Treatment with ZnOb NPs exhibited more potent fluorescence values than treatment with ZnOa NPs at 1 h. Moreover, significant overlaps (yellow) between cellular zinc ions and lysosomes were observed at all timepoints. Scale bar = 50µm. Magnification x600.

Sumei Yin,1 Xiangli Guan,1 Yaqi Zhang,1 Yang Li,1 Mary C Jobe,2 Md Zahir Ahmed3 1School of Teacher Education, Yuxi Normal University, Yuxi, 653100, People’s Republic of China; 2Department of Psychological and Brain Sciences, The George Washington University, Washington, DC, 20052, USA; 3School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of ChinaCorrespondence: Xiangli Guan, School of Teacher Education, Yuxi Normal University, Yuxi, 653100, People’s Republic of China, Tel +86-15758018670, Email guanxiangli@yxnu.edu.cn Md Zahir Ahmed, School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China, Tel +86-13919740494, Email ahmedzahirdu@gmail.comPurpose: This present study aims to explore the effects of work meaningfulness on primary school teachers’ self-reflection, self-efficacy and organizational commitment and their mechanisms of action.Methods: This study used a meaningfulness, self-reflection, self-efficacy, and organizational commitment measures. A total of 417 teachers from urban, rural, and mountainous elementary schools were recruited to complete the survey including the measures of work meaningfulness, self-reflection, self-efficacy, and organizational commitment. In this study, descriptive statistics were run using SPSS 26.0 and the relationship model between variables was tested with the SPSS macro program PROCESS.Results: The study found that work meaningfulness and self-efficacy independently predicted primary school teachers’ organizational commitment, but self-reflection did not significantly predict organizational commitment. It was found that there was a significant positive correlation between the four studied variables of work meaningfulness, self-efficacy, self-reflection, and organizational commitment with correlation coefficients ranging from 0.24 to 0.57. The study also found that work meaningfulness can directly predict elementary school teachers’ organizational commitment, and work meaningfulness can also indirectly predict elementary school teachers’ organizational commitment through self-efficacy and self-reflection.Conclusion: The results of this study are useful for understanding the value of enhancing the organizational commitment of primary school teachers from a social cognitive perspective, and have implications for how to build a stable, high-quality and dynamic primary school teaching force.Keywords: work meaningfulness, organizational commitment, self-reflection, self-efficacy, primary school teachers

Hongli Yang,1,&ast; Fajuan Rui,2,&ast; Rui Li,3,&ast; Shengxia Yin,4 Qi Xue,1 Xinyu Hu,5 Yayun Xu,5 Chao Wu,4 Junping Shi,6 Jie Li2,4 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji’nan, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing, People’s Republic of China; 3Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 5Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji’nan, People’s Republic of China; 6Department of Infectious Disease, The Affiliated Hospital of Hangzhou Normal University, Wenzhou Road, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China, Email lijier@sina.com Junping Shi, Department of Infectious Disease, The Affiliated Hospital of Hangzhou Normal University, Wenzhou Road, Hangzhou, Zhejiang, People’s Republic of China, Email 20131004@hznu.edu.cnAbstract: Background and Aims: Changes in living standards and diet structure, non-alcoholic fatty liver disease (NAFLD) is prevalent globally, including in Asia, where chronic hepatitis B (CHB) is endemic. As such, cooccurrence of NAFLD with CHB is common in Asia. However, the pathogenesis underlying the onset of fatty liver in CHB prognosis has not been fully elucidated. Therefore, we aimed to investigate the effects and mechanisms of lipotoxicity on hepatitis B virus (HBV) DNA replication.Methods: The expression of adenosine deaminase acting on RNA-1 (ADAR1) and miR-122 was evaluated in liver tissues from patients with CHB concurrent NAFLD. Palmitic acid-treated HepG2.2.15 cells were used as the cell model. The effect of lipotoxicity on HBV DNA replication was evaluated in vitro by transfecting the ADAR1 overexpression or knockdown lentiviral vector into HepG2.2.15 cells, respectively. qRT-PCR, western blotting and immunofluorescence were performed to determine ADAR1 expression.Results: The expression of ADAR1 in the liver tissues of CHB patients with concurrent NAFLD was significantly down-regulated compared with that in CHB patients. Enforced expression of ADAR1 inhibited the HBV DNA replication, whereas ADAR1 knockdown resulted in increased HBV DNA expression in palmitic acid - treated HepG2.2.15 cells. Additionally, ADAR1 inhibited the HBV DNA replication by upregulating miR-122, which is most abundant in the liver and mainly inhibits HBV DNA replication.Conclusions: ADAR1 may act as a suppressor of HBV replication in palmitic acid -treated HepG2.2.15 cells by increasing miR-122 levels. Thus, ADAR1 may serve as a potential biomarker and therapeutic target for CHB with concurrent NAFLD.Graphical Abstract: Keywords: chronic hepatitis B, non-alcoholic fatty liver disease, ADAR1, miR-122, HBV DNA

Yin S, Lin X. Int J Gen Med. 2021;14:27–39. We, the Editors and Publisher of International Journal of General Medicine, have retracted the following article. Following publication of the article, concerns were raised about the duplication of an image from Figures 4 with images from another unrelated article. Specifically, The image for Figure 4H, HSC-1, TIMP3 si, has been duplicated with the image for Figure 7H, HL-60, miR-206 inh+NC, from Wang N, Feng Y, Xie J, Han H, Dong Q, Wang W. Long Non-Coding RNA ZNF667-AS1 Knockdown Curbs Liver Metastasis in Acute Myeloid Leukemia by Regulating the microRNA-206/AKAP13 Axis. Cancer Manag Res. 2020;12:13285-13300. https://doi.org/10.2147/CMAR.S269258. In addition, the images for Figure 2D, 0h and 24h, HSC-1, miR-21 inhibitor have been duplicated with images for Figure 2D, 0h, A431, miR-21 control and 24h, A431, miR-21 inhibitor, respectively. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Shuying Yin,1,2 Min Hu,1 Wen Chen1 1Department of Health Economics, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Department I, Shenzhen Health Development Research and Data Management Center, Shenzhen, People’s Republic of ChinaCorrespondence: Wen Chen; Min Hu, The Department of Health Economics, School of Public Health, Fudan University, No. 187 Box, 138 Yixueyuan Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13818325486 ; +86 17717031079, Email wenchen@fudan.edu.cn; humin@fudan.edu.cnPurpose: Outpatients have choices of providers in the hierarchical health service delivery system of China. Understanding how quality perceptions and outpatient experience affect the choice of health facility would help inform decisions about priorities for action aimed at guiding the use of primary care. This study examines how quality perceptions of outpatient service affect the facility level choice in rural China.Methods: Household surveys were conducted in 2011, 2012 and 2015 in Ningxia Hui Autonomous Region, China. We selected 968 respondents as the study sample, who had at least two outpatient visits to the public health facilities during each survey period. Prior quality perceptions of the outpatient service at the village clinics, township centers, and county hospitals were reported on an 8-item Quality Indicator questionnaire. Experienced quality perception from the first outpatient visit was also reported. The outcome of interest was outpatients’ facility level choices. We used regression and mediation analysis to explore whether and how outpatient experience at a specific health facility would mediate the relationship between prior quality perceptions and the facility level choice.Results: Overall, the quality perception was positively and significantly associated with outpatients’ staying at the same or lower levels of care (β=0.265, P=0.007). This effect was fully mediated by experienced quality perception (z=2.985, P=0.003). The indirect effect was significant for three particular dimensions, including quality perceptions of the environment (β=0.075, P=0.025), doctor-patient communication (β=0.065, P=0.022), and physician ability (β=0.062, P=0.021).Conclusion: Outpatient quality perceptions—especially positive perceptions regarding environment, doctor-patient communication, and physician ability—could contribute to minimizing upward referral via improvement in outpatient experience. Policymakers and health care providers may need to therefore optimize outpatient experience as they push to develop a more locally responsive primary care system.Keywords: perceived quality, choice of provider, outpatient care, questionnaire, China

Ruhan Liu,1,2,&ast; Chenyang Li,1,&ast; Huajun Xu,1 Kejia Wu,1 Xinyi Li,1 Yupu Liu,1 Jie Yuan,1 Lili Meng,1 Jianyin Zou,1 Weijun Huang,1 Hongliang Yi,1 Bin Sheng,2 Jian Guan,1 Shankai Yin1 1Department of Otolaryngology Head and Neck Surgery and Shanghai Key Laboratory of Sleep Disordered Breathing & Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Sheng; Jian Guan, Tel +86 13124853285, Email shengbin@sjtu.edu.cn; guanjian0606@sina.comPurpose: Misdiagnosis and missed diagnosis of sleep-disordered breathing (SDB) is common because polysomnography (PSG) is time-consuming, expensive, and uncomfortable. The use of recording methods based on the oxygen saturation (SpO2) signals detected by wearable devices is impractical and inaccurate for extracting signal features and detecting apnoeic events. We propose a method to automatically detect the apnoea-based SpO2 signal segments and compute the apnoea–hypopnea index (AHI) for SDB screening and grading.Patients and Methods: First, apnoea-related desaturation segments in raw SpO2 signals were detected; global features were extracted from whole night signals. Then, the SpO2 signal segments and global features were fed into a bi-directional long short-term memory convolutional neural network model to identify apnoea-related and non-apnoea-related events. The apnoea-related segments were used to assess the AHI.Results: The model was trained on 500 individuals and tested on 8131 individuals from two public hospitals and one private centre. In the testing data, the classification accuracy for apnoea-related segments was 84.3%. Individuals with SDB (AHI 15) were identified with a mean accuracy of 88.95%.Conclusion: Using automatic SDB detection based on SpO2 signals can accurately screen for SDB.Keywords: sleep apnea hypopnea syndrome, AHI, SDB severity classification, Bi-LSTM-CNN, desaturation events

Shuai Yin,1,&ast; Zhen-Hua Zhang,1,&ast; Yi-Niu Chang,2,&ast; Jin Huang,2 Ming-Li Wu,1 Qi Li,1 Jin-Qi Qiu,1 Xiao-Dong Feng,1,2 Nan Wu2 1Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China; 2School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Dong Feng, Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, No. 19, Renmin Road, Zhengzhou, 450000, People’s Republic of China, Tel +8615303828605, Email fxd0502@163.com Nan Wu, School of Rehabilitation Medicine, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, People’s Republic of China, Tel +8613540484550, Email wunanwy@126.comPurpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA.Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data.Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA.Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.Keywords: knee osteoarthritis, acupuncture, cognitive control network, randomized controlled trial

Chao Jiang,1,2,&ast; Si Yin,1,&ast; Jianmin Wei,3,&ast; Weigong Zhao,1 Xiaohui Wang,1,2 Yongyuan Zhang,1,2 Dingjun Hao,2 Heng Du1 1Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Spine Surgery, Baoji City Hospital of Traditional Chinese Medicine, Baoji, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heng DuDepartment of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaEmail drdu18@126.comObjective: The purpose of this study was to introduce and evaluate the early clinical outcomes of the full-endoscopic posterior lumbar interbody fusion (Endo-PLIF) technique with epidural anesthesia (EA) for single-segment lumbar degenerative diseases.Methods: In this retrospective case series study, we explored the feasibility and effectiveness of the Endo-PLIF with EA for single-segment lumbar degenerative diseases. Between March 2018 and January 2019, a series of 24 patients with single-segment lumbar degenerative diseases underwent Endo-PLIF surgery and were followed up for a minimum of 12 months (15.21± 2.27 months). Clinical outcomes including visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) were evaluated preoperatively, and postoperatively at 3 days and at 3, 6, and 12-months.Results: All patients underwent successful single-segment Endo-PLIF surgery. The mean operation time was 209.17± 39.49 min, and average amount of bleeding was 43.33± 14.87 mL. The VAS for lower extremity pain and back pain significantly improved at 3 days, and at 3, 6, 12 months compared with preoperative, respectively. The ODI scores decreased from 42.04± 3.96 to 12.75± 2.71 (P< 0.001) at preoperative and 12 months postoperatively, respectively. The SF-36 Physical Component Scores (PCS) improved from 34.96± 4.63 preoperatively to 52.08± 6.05 (P< 0.001) at 12 months postoperatively. Additionally, the SF-36 Mental Component Scores (MCS) improved from 39.38± 5.70 at preoperative to 53.13± 5.97 (P< 0.001) at 12 months postoperatively. Two patients experienced dysesthesia, and one patient had a wound infection.Conclusion: Endo-PLIF with EA is a feasible and valuable technique for the treatment of single-segment lumbar degenerative diseases in selected patients.Keywords: full-endoscopic posterior lumbar interbody fusion, lumbar degenerative disease, lumbar fusion, clinical outcome

Wu P, Wang PL, Ma B, et al. Cancer Manag Res. 2018;10:4759–4771 The Editor and Publisher of Cancer Management and Research are issuing an Expression of Concern for the published article. Following publication concerns have been raised over the integrity of the articles content. As we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern.

Yuanyuan Liu,1,2 Songmei He,2 Sichun Yin,2 Qingyang Zhong,2 Jianbo Zhong,2 Xiaoyong Zhang,1 Rong Fan,1 Jinlin Hou1,3 1Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Infectious Diseases, Dongguan People’s Hospital, Dongguan, Guangdong, People’s Republic of China; 3Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Jinlin HouDepartment of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20 61641941Fax +86 20 62786530Email jlhousmu@163.comObjective: The detection of dual-positivity for both hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) is not typically performed for patients with hepatitis B virus (HBV). This cross-sectional study was designed to figure out the prevalence of dual-positivity for both HBeAg and anti-HBe (DEP) among hospitalized patients with chronic hepatitis B virus infection (C-HBVI).Patients and Methods: Data from 2820 cases with C-HBVI from two centers in China were retrospectively analyzed. Univariate and multivariate logistic regression analyses were undertaken to identify the risk factors for liver fibrosis (LF) and acute-on-chronic liver failure (ACLF).Results: There were 165 (5.9%), 688, and 1903 patients in DEP, HBeAg+/anti-HBe-, and HBeAg-/anti-HBe+ groups, respectively. The DEP patients’ median age was 43.6 years old and 71.5% of them were male. They had higher levels of alanine transaminase, total bilirubin, and international normalized ratio. Furthermore, DEP cases had a higher proportion of liver cirrhosis, and it was associated with non-invasive testing of LF, including aspartate transaminase (AST)-to-platelet ratio index (APRI) > 1.5 (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.27– 3.03, P = 0.002) and fibrosis-4 (FIB-4) score > 1.45 (OR = 2.07, 95% CI: 1.28– 3.34, P = 0.003). DEP also contributed to the elevated risk of ACLF (OR = 4.80, 95% CI: 2.02– 11.39, P < 0.001).Conclusion: DEP cases are at higher risks of LF and ACLF than other patients with HBV infection. A fast diagnosis and an active monitoring of liver diseases for DEP patients are extremely vital.Keywords: hepatitis B e antigen, hepatitis B e antibody

Sheng Yin,1,&ast; Wen Gao,2,&ast; Peipei Shi,1 Meili Xi,1 Wenbin Tang,1 Jiarong Zhang1 1Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Gynaecologic Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiarong ZhangDepartment of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Fenglin Road, 180#, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel +86 21-64041990Email zhang.jiarong@zs-hospital.sh.cnPurpose: Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC.Patients and Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan–Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test.Results: Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients’ characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups.Conclusion: Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.Keywords: laparoscopic surgery, early-stage ovarian clear cell cancer, prognosis

Xiaolong Zhao,1– 3,&ast; Huajun Xu,1,3,&ast; Chuan Dong,2,&ast; Jiangang Fan,2 Gang He,2 Jianyin Zou,1,3 Lili Meng,1,3 Huaming Zhu,1,3 Kaiming Su,1,3 Mingpo Yang,4 Hongliang Yi,1,3 Jian Wang,5 Shankai Yin,1,3 Jian Guan1,3 1Department of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, People’s Republic of China; 4Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5School of Communication Science and Disorders/Physiol & Biophysics, Dalhousie University, Halifax, NS, Canada&ast;These authors contributed equally to this workCorrespondence: Shankai Yin; Jian Guan Email skyin@sjtu.edu.cn; guanjian0606@sina.comBackground: Cardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood.Methods: In total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose–response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA.Results: The RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function.Conclusion: These results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.Keywords: obstructive sleep apnea, autonomic nervous system, cardiac autonomic neuropathy, metabolism, heart rate variability

Xiang Li,1,* Guodong Wang,2,* Kun Yan,1 Shanshan Yin,1 Hongzhi Wang,2 Yanjie Wang,1 Xiumei Bai,1 Yanfen Shen2 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), ICU, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun YanKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100042, People’s Republic of ChinaTel + 86 13611176073Fax +86 10-88196195Email ydbz@vip.sina.comHongzhi WangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), ICU, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of ChinaTel/Fax +86 10-88196112Email doctorwhz@163.comPurpose: A peripherally inserted central catheter (PICC) is associated with venous thromboembolism (VTE) especially in patients suffering from cancer. We analyzed the incidence, risk factors, and patterns of PICC-related VTE in cancer patients.Patients and Methods: Patients with cancer who underwent PICC placement were evaluated retrospectively. Routine, prospective ultrasound post-PICC placement was used for asymptomatic and symptomatic patients to identify VTE. Multivariable logistic regression models with odds ratios (ORs) were used to examine VTE risk factors.Results: Of 2353 PICCs placed, 165 patients (7.01%) developed PICC-related VTE with a median thrombosis time of 12 days. After adjustment of multivariable analysis, patients with PICC-related VTE were more likely to have a ratio of PICC diameter:vein diameter > 0.35 (adjusted OR, 1.689; 95% CI, 1.023– 2.789) and high level of triglycerides (1.561; 1.096– 2.223). The prevalence of A (adjusted OR, 1.680; 95% CI, 1.009– 2.798), B (1.835; 1.137– 2.961), and AB (3.275; 1.840– 5.829) blood group was significantly higher than that of the O blood group in VTE patients. Venous recanalization was observed in 44.8% (74/165) patients after anticoagulation therapy, and more often in patients with combined deep VTE than in patients with isolated superficial VTE (OR, 17.942; 95% CI, 5.427– 59.316). The recanalization time was 20± 5 (range, 10– 31) days.Conclusion: The non-O blood group, larger ratio of PICC diameter:vein diameter, and high level of triglycerides were significantly associated with PICC-related VTE. Almost half of cases of PICC-related deep VTE could be reversed by anticoagulation treatment.Keywords: recanalization, ultrasound, venous thromboembolism

Junhong Li, Xingwang Zhou, Yufan Xiang, Shuxin Zhang, Wentao Feng, Yunbo Yuan, Yanhui Liu, Senlin Yin Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of ChinaCorrespondence: Senlin Yin Email enforest@gmail.comObjective: To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics.Patients and Methods: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan–Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models.Results: A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤ 80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC.Conclusion: FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.Keywords: fibrinogen to albumin ratio, FAR, fibrinogen, albumin, glioblastoma, prognosis

Jianchang Qian,1,* Sihui Yin,1,* Lin Ye,1 Zhe Wang,2 Sheng Shu,1,3 Zhenxin Mou,1,3 Mingjiang Xu,1 Nipon Chattipakorn,4 Zhiguo Liu,1 Guang Liang1,3,5 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 4Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang Liang; Zhiguo LiuChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of ChinaTel/Fax +86-577-86699396Email wzmcliangguang@163.com; lzgcnu@163.comAim: Elevated inflammatory signaling has been shown to play an important role in diabetic kidney disease (DKD). We previously developed a new anti-inflammatory compound LG4. In the present study, we have tested the hypothesis that LG4 could prevent DKD by suppressing inflammation and identified the underlying mechanism.Methods: Streptozotocin-induced type 1 diabetic mice were used to develop DKD and evaluate the effects of LG4 against DKD. To identify the potential targets of LG4, biotin-linked LG4 was synthesized and subjected to proteome microarray screening. The cellular mechanism of LG4 was investigated in HG-challenged SV40MES13 cells.Results: Although LG4 treatment had no effect on the body weight and blood glucose levels, it remarkably reversed the hyperglycemia-induced pathological changes and fibrosis in the kidneys of T1DM mice. Importantly, hyperglycemia-induced renal inflammation evidenced by NF-κB activation and TNFα and IL-6 overexpression was greatly ameliorated with LG4 treatment. Proteosome microarray screening revealed that JNK and ERK were the direct binding proteins of LG4. LG4 significantly reduced HG-induced JNK and ERK phosphorylation and subsequent NF-κB activation in vivo and in vitro. In addition, LG4 did not show further anti-inflammatory effect in HG-challenged mesangial cells with the presence of JNK or ERK inhibitor.Conclusion: LG4 showed renoprotective activity through inhibiting ERK/JNK-mediated inflammation in diabetic mice, indicating that LG4 may be a therapeutic agent for DKD.Keywords: indole-2-carboxamide derivative, diabetic kidney disease, inflammation, MAPK, NF-κB

Shuyang Sun,1,2 Ziqiang Ding,1 Xiaomei Yang,1,3 Xinyue Zhao,1,3 Minlong Zhao,1,2 Li Gao,1,3 Qu Chen,1,2 Shenxia Xie,1,4 Aiqun Liu,1 Shihua Yin,1 Zhiping Xu,5 Xiaoling Lu1,2 1International Nanobody Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2School of Stomatology, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 5Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD, 4072, AustraliaCorrespondence: Xiaoling LuNanobody Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaTel/Fax +86 771-2387 518Email luxiaoling@gxmu.edu.cnZhiping XuAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD, 4072, AustraliaEmail gordonxu@uq.edu.auAbstract: The development of monoclonal antibody treatments for successful tumor-targeted therapies took several decades. However, the efficacy of antibody-based therapy is still confined and desperately needs further improvement. Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size (∼ 15kDa), excellent solubility, superior stability, ease of manufacture, quick clearance from blood, and deep tissue penetration, which gain increasing acceptance as therapeutical tools and are considered also as building blocks for chimeric antigen receptors as well as for targeted drug delivery. Thus, one of the promising novel developments that may address the deficiency of monoclonal antibody-based therapies is the utilization of nanobodies. This article provides readers the significant factors that the structural and biochemical properties of nanobodies and the research progress on nanobodies in the fields of tumor treatment, as well as their application prospect.Keywords: nanobody, drug delivery, immunotherapy, CAR-T, tumor treatment

Shuhong Yin, Xiuying Lin Department of Dermatology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People’s Republic of ChinaCorrespondence: Xiuying Lin Tel/Fax +86-452-2697320Email xiuyinglin011602@163.comBackground: Though the therapeutic potentials of microRNAs (miRNAs) are extensively explored in cutaneous squamous cell carcinoma (CSCC), the concrete function of miR-21 in this disorder has not been thoroughly comprehended. Therein, this work is launched to clarify the miR-21-pivoted mechanism in CSCC from the perspective of tissue inhibitor of metalloproteinases-3 (TIMP3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.Methods: Microarray-based analysis was utilized to screen out miR-21 with the most up-regulated expression in CSCC tissues. The relation between miR-21 and TIMP3 expression in tissues, and the overall survival of CSCC patients was evaluated. Loss-of-function assays were performed in cells to explore the independent and combined functions of miR-21 and TIMP3 in CSCC cell progression. Mice were injected with miR-21 inhibitor or TIMP3 si for identifying their roles in tumor formation and liver metastasis. The mechanism among miR-21, TIMP3 and PI3K/AKT pathway was interpreted.Results: MiR-21 was up-regulated while TIMP3 was down-regulated in CSCC tissues, which were connected with unsatisfactory survival of patients. Down-regulating miR-21 inhibited CSCC cell progression and retarded CSCC tumor formation and metastasis in mice. Silencing of TIMP3 reversed the effects of miR-21 down-regulation on CSCC progression. Besides, down-regulating miR-21 inhibited PI3K/AKT pathway activation in CSCC cells via mediating TIMP3.Conclusion: It is elucidated that miR-21 depletion impedes CSCC cell invasion and metastasis via enhancing TIMP3 and suppressing PI3K/AKT pathway activation.Keywords: cutaneous squamous cell carcinoma, microRNA-21, tissue inhibitor of metalloproteinases-3, phosphatidylinositol 3-kinase/protein kinase B pathway, metastasis

Dumping or disposal of fly ash causes environmental pollution and huge waste of valuable metals. In this work, carbothermic reduction of fly ash under normal pressure to produce Al-Si-Fe alloy, and thermal reduction of magnesia to produce magnesium in vacuum with Al-Si-Fe alloy were investigated. In addition, the surface morphology and composition of Al-Si-Fe alloy and magnesium were studied by means of SEM-EDS and XRD. Based on the thermodynamic analysis, it was found that AlN and SiO2 lowered down the reduction temperature of SiC and Al4C3, respectively. Increase of temperature and decrease of vacuum degree promotes the thermal reduction of magnesia. Results showed that the recovery rate ranked Fe, Si, and Al in a descending order. The evaporation loss of gaseous SiO and Al2O reduced the recovery of Si and Al. Al-Si-Fe alloy containing 33.12% Al, 48.73% Si, and 6.41% Fe is obtained under the optimal conditions. Magnesium with the content of 94.87% is prepared using the obtained Al-Si-Fe alloy as a reductant. The nucleation rate is less than the growth rate during the condensation of magnesium vapor.

Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCs’ pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genes’ functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis.

Fei Zhang,1 Chuanxin Duan,1 Shucheng Yin,2 Ying Tian1 1Department of Otolaryngology, Maternal and Child Health Care Hospital of Hubei Province and Women and Children’s Hospital of Hubei Province, Wuhan 430070, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaCorrespondence: Ying Tian Email tianying_520@qq.comBackground: Epithelial–mesenchymal transition (EMT) is a major actor modulating the metastasis of nasopharyngeal carcinoma (NPC). Increasing evidence indicates that microRNAs (miRs) are the important regulators of EMT program. However, the potential roles and underlying mechanisms of miR‑379-5p in regulating EMT of NPC cells remain unclear.Methods: miR-379-5p expression levels in human NPC tissues and cell lines were detected via quantitative real-time PCR (qRT-PCR). Then, the correlations between miR-379-5p expression in NPC tissues and clinicopathologic features and patients’ prognosis were analyzed. The effect of miR-379-5p on the expression of EMT markers in NPC cells was evaluated by Western blot and qRT-PCR. NPC cells’ migration and invasion were evaluated in vitro by Transwell migration and invasion assays, respectively. The target of miR-379-5p was predicted with three publicly available databases and further validated with dual-luciferase reporter assay, qRT-PCR, and Western blot.Results: The expression of miR-379-5p was significantly decreased in NPC tissues, and its low expression was significantly associated with multiple unfavorable clinicopathological factors and poor prognosis of NPC patients. Meanwhile, miR-379-5p was downregulated in NPC cell lines, and its exotic expression inhibited EMT to reduce the migration and invasion of NPC cells. Furthermore, Y-box binding protein 1 (YBX1) was identified and validated as a direct target of miR-379-5p, and restoring YBX1 expression could reverse the inhibitive effect of miR-379-5p on NPC cell EMT, migration and invasion.Conclusion: Taken together, our findings indicate that miR-379-5p inhibits the EMT of NPC cells to reduce their migration and invasion abilities by post-transcriptionally suppressing YBX1 expression, providing a novel potential treatment target for NPC patients.Keywords: miR-379-5p, nasopharyngeal carcinoma, YBX1, EMT, migration, invasion

Wenquan Ding,1,* Xueyuan Li,1,* Jiadong Pan,1 Peixun Zhang,2 Shanqing Yin,1 Xianting Zhou,1 Junjie Li,1 Liping Wang,1,3 Xin Wang,1 Jianghui Dong1,3 1Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People’s Republic of China; 2Department of Trauma Orthopedics, Peking University People’s Hospital, Beijing 100044, People’s Republic of China; 3School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia*These authors contributed equally to this workCorrespondence: Xin WangDepartment of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No.6 Hospital, Ningbo 315040, People’s Republic of ChinaTel/Fax +86574-87996193Email dr.wangxin@hotmail.comJianghui DongSchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, AustraliaTel +618 8302 2715Fax +618 8302 1087Email Jianghui.dong@mymail.unisa.edu.auPurpose: Complete high ulnar nerve injury can cause serious sequelae, including residual sensation and loss of movement and especially dysfunction of the intrinsic muscles of the hand. As a solution to treat complete high ulnar nerve injury, we proposed a new repair method for ulnar nerve injury based on nerve-magnified regeneration.Methods: Twenty-two patients with complete division of the ulnar nerve at a high level who were treated from May 2013 to December 2016 were divided into two groups. The proposed repair method for complete high ulnar nerve injury was performed in group I (11 patients), while the traditional repair method, ie, repair of the original injury site of the ulnar nerve, was used in group II (11 patients).Results: The results showed no significant difference in the mean sensory scores assigned by the Highet-Zachary scheme (the Highet Scale) between the two groups. The mean Highet Scale score of muscle strength for the first dorsal interosseus muscle was significantly better in group I than that in group II (p=0.010). In group I, 10 of 11 patients were graded as M4 or M5. Grip strength, pinch strength, and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were significantly better in group I than those in group II (p< 0.01).Conclusion: Therefore, this method for complete high ulnar nerve injury based on nerve-magnified regeneration can shorten the path of motor nerve regeneration, effectively reduce atrophy of the intrinsic muscles of the hand, and provide better hand function.Keywords: nerve magnified regeneration, ulnar nerve injury, nerve repair, peripheral nervous system

Xiaoyu Xu,1 Songcheng Yin,2,3 Hongling Guo,1 Mengxiong Li,1 Zhirong Qian,4 Xiaohui Tian,1 Tian Li11Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 2Center for Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 4Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaBackground: The number of published randomized clinical trials (RCTs) using targeted maintenance therapy for newly diagnosed epithelial ovarian cancer is increasing. Our objective was to evaluate the comparative effectiveness of each maintenance therapy using a network meta-analysis.Materials and methods: A systematic search for RCTs was conducted using Medline, Embase, and CENTRAL databases followed by a Bayesian network meta-analysis. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS). Pooled hazard ratios (HRs) with 95% credible intervals (95% CrIs) were used to estimate outcomes.Results: A total of 11 RCTs involving 6631 patients were included. Network meta-analysis showed that pure maintenance therapy with pazopanib resulted in a significantly better PFS compared with placebo (HR, 0.77; 95% CrI, 0.65–0.92). Bevacizumab-throughout treatment was also associated with a better PFS (HR, 0.76, 95% CrI, 0.69–0.84). However, anti-CA-125 monoclonal antibodies (abagovomab and oregovomab) showed no significant survival benefit. Moreover, combined analysis showed that targeted-throughout was not significantly superior to pure targeted maintenance therapy for PFS and OS. Stratified analysis showed paralleled results with no significant difference between pazopanib pure maintenance and bevacizumab-throughout treatments.Conclusion: Our study showed a survival advantage conferred by pazopanib and bevacizumab as maintenance therapy in newly diagnosed epithelial ovarian cancer. Further clinical trials are essential to both determine the effect of bevacizumab in the maintenance stage and identify the specific subgroup(s) that benefit.Keywords: targeted treatment, maintenance therapy, ovarian cancer, network meta-analysis

Zhen Chen,* Kai Wang,* Hao Lu, Dong Xue, Min Fan, Qianfeng Zhuang, Shuai Yin, Xiaozhou He, Renfang Xu Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China *These authors contributed equally to this work Purpose: In the present study, we aimed to evaluate the prognostic significance of the systemic inflammation response index (SIRI), which was defined based on peripheral blood counts of neutrophils, lymphocytes, and monocytes, in patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC).Patients and methods: The prognostic value of SIRI was evaluated in a primary cohort consisting of 414 patients with localized or locally advanced CCRCC and then further validated in an independent cohort composed of 168 patients.Results: Kaplan–Meier survival analyses of both cohorts revealed that CCRCC patients with high SIRI levels exhibited poorer overall survival (OS) and cancer-specific survival (CSS) compared with those with low SIRI levels. Furthermore, univariate and multivariate analyses identified SIRI as a significant independent predictor for both OS (HR: 4.853; 95% CI: 2.362–9.972; P

Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.

Jia Liu,1 Yiyuan Kang,1 Suhan Yin,1 Bin Song,2 Limin Wei,3 Liangjiao Chen,4 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 2Department of Stomatology, Guizhou Provincial People’s Hospital, Guiyang, 3Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 4Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Due to the widespread applications of zinc oxide nanoparticles (ZnO NPs), the potential exposure of workers, consumers, and scientists to these particles has increased. This potential for exposure has attracted extensive attention in the science community. Many studies have examined the toxicological profile of ZnO NPs in the immune system, digestive system, however, information regarding the toxicity of ZnO NPs in the nervous system is scarce. In this study, we detected the cytotoxicity of two types of ZnO NPs of various sizes – ZnOa NPs and ZnOb NPs – and we characterized the shedding ability of zinc ions within culture medium and the cytoplasm. We found that reactive oxygen species played a crucial role in ZnO NP-induced cytotoxicity, likely because zinc ions were leached from ZnO NPs. Apoptosis and cytoskeleton changes were also toxic responses induced by the ZnO NPs, and ZnOb NPs induced more significant toxic responses than ZnOa NPs in SHSY5Y cells. In conclusion, ZnO NPs induced toxic responses in SHSY5Y cells in a size-dependent manner, which can probably be attributed to their ion-shedding ability. Keywords: zinc oxide, nanoparticles, SHSY5Y cells, reactive oxygen species, apoptosis, cell cytoskeleton

In traditional body-centered cubic (bcc) metals, the core properties of screw dislocations play a critical role in plastic deformation at low temperatures. Recently, much attention has been focused on refractory high-entropy alloys (RHEAs), which also possess bcc crystal structures. However, unlike face-centered cubic high-entropy alloys (HEAs), there have been far fewer investigations into bcc HEAs, specifically on the possible effects of chemical short-range order (SRO) in these multiple principal element alloys on dislocation mobility. Here, using density functional theory, we investigate the distribution of dislocation core properties in MoNbTaW RHEAs alloys, and how they are influenced by SRO. The average values of the core energies in the RHEA are found to be larger than those in the corresponding pure constituent bcc metals, and are relatively insensitive to the degree of SRO. However, the presence of SRO is shown to have a large effect on narrowing the distribution of dislocation core energies and decreasing the spatial heterogeneity of dislocation core energies in the RHEA. It is argued that the consequences of the mechanical behavior of HEAs is a change in the energy landscape of the dislocations, which would likely heterogeneously inhibit their motion.