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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

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

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.

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’.

Nb3Sn accelerator magnets are poised to enable the luminosity upgrade of the Large Hadron Collider (LHC) at CERN, improving its potential for exploring physics beyond the standard model of particle physics. The prototype Nb3Sn magnets consistently need 10-25 quenches to achieve their best performance. A hypothesis is that the long training of these magnets may at least be partially induced by epoxy cracking and bonding failures. In 2018, we showed that several existing epoxies have a higher toughness and less tendency to crack at low temperatures than CTD-101K, the epoxy resin with which almost all Nb3Sn accelerator magnets have been impregnated. Here we explore a new high toughness formulation for reducing quench training of Nb3Sn accelerator magnets, through combining two amine curing agents to achieve a good glass transition temperature $(T_{g})$, adding a viscosity reducer to achieve low viscosity, and experimenting a coupling agent for improved bonding strengths. We report results of comprehensive materials tests, including thermal shock, tensile, compressive, shear tests, viscosity and $T_{g}$ tests.

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

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

Bouligand structures are widely observed in natural materials; elasmoid fish scales and the exoskeleton of arthropods, such as lobsters, crabs, mantis shrimp and insects, are prime examples. In fish scales, such as those of the Arapaima gigas, the tough inner core beneath the harder surface of the scale displays a Bouligand structure comprising a layered arrangement of collagen fibrils with an orthogonal or twisted staircase (or plywood) architecture. A much rarer variation of this structure, the double-twisted Bouligand structure, has been discovered in the primitive elasmoid scales of the coelacanth fish; this architecture is quite distinct from “modern” elasmoid fish scales yet provides extraordinary resistance to deformation and fracture. Here we examine the toughening mechanisms created by the double-twisted Bouligand structure in comparison to those generated by the more common single Bouligand structures. Specifically, we have developed an orientation-dependent, hyperelastic, phase-field fracture mechanics method to computationally examine the relative fracture toughness of elasmoid fish scales comprising single vs. double-twisted Bouligand structures of fibrils. The model demonstrates the critical role played by the extra inter-bundle fibrils found in coelacanth fish scales in enhancing the toughness of Bouligand-type structures. Synthesis and fracture tests of 3-D printed Bouligand-type materials are presented to support the modeling and complement our understanding of the fracture mechanisms in Bouligand-type structures.

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