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Yinlin Wang,1 Xinyue Zhang,2 Haiyan Zheng,1 Zihuai Zhou,1 Si Li,1 Jimin Jiang,1 Mingxing Li,1 Baiping Fu1 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, People’s Republic of China; 2School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Baiping Fu; Mingxing Li, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, People’s Republic of China, Email fbp@zju.edu.cn; 7315019@zju.edu.cnObjective: This study was to investigate a novel antibacterial biomimetic mineralization strategy for exploring its potential application for root canal disinfection when stabilized cerium oxide was used.Material and Methods: A biomimetic mineralization solution (BMS) consisting of cerium nitrate and dextran was prepared. Single-layer collagen fibrils, collagen membranes, demineralized dentin, and root canal system were treated with the BMS for mineralization. The mineralized samples underwent comprehensive characterization using various techniques, including transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared spectroscopy (FTIR), scanning transmission electron microscopy (STEM), selected-area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and micro-CT. Additionally, the antimicrobial properties of the BMS and the remineralized dentin were also analyzed with broth microdilution method, live/dead staining, and SEM.Results: Cerium ions in the BMS underwent a transformation into cerium oxide nanoparticles, which were deposited in the inter- and intra-fibrillar collagen spaces through a meticulous bottom-up process. XPS analysis disclosed the presence of both Ce (III) and Ce (IV) of the generated cerium oxides. A comprehensive examination utilizing SEM and micro-CT identified the presence of cerium oxide nanoparticles deposited within the dentinal tubules and lateral canals of the root canal system. The BMS and remineralized dentin exhibited substantial antibacterial efficacy against E. faecalis, as substantiated by assessments involving the broth dilution method and live/dead staining technique. The SEM findings revealed the cell morphological changes of deceased E. faecalis.Conclusion: This study successfully demonstrated antibacterial biomimetic mineralization as well as sealing dentinal tubules and lateral branches of root canals using cerium nitrate and dextran. This novel biomimetic mineralization could be used as an alternative strategy for root canal disinfection.Keywords: cerium oxide, dextran, biomimetic mineralization, root canal disinfection

Hua-Song Shentu,1 Yi-Hua Chen,1 Zhen-Yu Cheng,1 Bin Fu,1 Yuan-Hao Fu,1 Shu-Feng Zheng,2 Chan Li1 1Department of Neurosurgery, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Shu-Feng Zheng, Department of Endocrinology, Jinhua People’s Hospital, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, 321000, People’s Republic of China, Email m13819976688@163.comBackground: The inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) may regulate immunity and inflammation. The current study was conducted to determine its role as a biomarker for reflecting the severity and predicting outcomes of intracerebral hemorrhage (ICH).Methods: In this prospective cohort study, 185 patients with supratentorial ICH were enrolled, among whom 62 had blood obtained not only at admission but also on days 1, 3, 5, 7, 10, and 14. In addition, 62 healthy controls underwent blood collection at the start of the study. The serum ITIH4 levels were then quantified. We recorded early neurological deterioration (END) and poor prognosis (modified Rankin Scale [mRS] scores of 3– 6]) six months after ICH.Results: Serum ITIH4 levels decreased prominently in the early phase after ICH, continued to decline until day 5, then gradually increased until day 14, and were significantly lower during 14 days in patients than in controls. Serum ITIH4 levels on admission were independently associated with serum C-reactive protein levels, National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume. Admission serum ITIH4 levels were independently associated with mRS scores, END, and poor prognosis. No substantial differences existed in the areas under the receiver operating characteristic curve of END and poor prognosis prediction between the serum ITIH4 levels, NIHSS scores, and hematoma volume. Prediction models, in which serum ITIH4 levels, NIHSS scores, and hematoma volume were integrated, were relatively reliable and stable using a series of statistical methods. In addition, the prediction model of poor prognosis had a higher discriminatory ability than the NIHSS scores and hematoma volume alone.Conclusion: A dramatic decline in serum ITIH4 levels during the early period following ICH is independently related to the inflammatory response, stroke severity, and poor neurologic outcomes, suggesting that serum ITIH4 may be a useful prognostic biomarker of ICH.Keywords: inter-alpha-trypsin inhibitor heavy chain 4, intracerebral hemorrhage, early neurologic deterioration, prognosis, severity, biomarkers

Ning Luo,1,* Rongrong Li,2,* Baitian Fu,1 Yichen Zeng,1 Jianqiao Fang1,2 1The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianqiao Fang, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China, Email fangjianqiao7532@163.comBackground: Evidence has shown that dry needling (DN) is effective for myofascial pain syndrome (MPS). However, bibliometrics has rarely been used to analyze the literature related to DN for MPS. The purpose of this study is to provide a systematic overview of global frontiers and research hotspots of DN in the treatment of MPS from 2000 to 2022.Methods: A search was conducted on Web of Science Core Collection (WoS CC) for literature on DN for MPS from 2000 to 2022. Based on the basic information provided by WoS CC, CiteSpace software was used to conduct bibliometric analysis of the countries, institutions, categories, journals, authors, references and keywords involved in this topic.Results: A total of 458 papers were obtained, with the number of publications increasing over time. Journal of Bodywork and Movement Therapies (31) was the most productive journal based on the number of publications, while Arch Phys Med Rehab (329) was the most co-cited journal. The most productive countries and institutions were USA (112) and Universidad Rey Juan Carlos (39), respectively. Fernandez-de-las-penas, Cesar has the highest number of publications (24) and Simons DG, who was an author with the highest number of citations (250). The article published by Gattie et al (co-citations: 65), and Mejuto-Vazquez et al (centrality: 0.36) were the most representative and symbolic. Based on the co-cited literature and keywords, myofascial trigger point, research methods, and acupuncture were the hot research topics and trends in the field.Conclusion: The current status and trends in clinical research of DN for MPS are revealed according to the results of this bibliometric study, which may facilitate researchers to identify hot topics and new directions for future research.Keywords: dry needling, myofascial pain syndrome, bibliometric analysis, research trends, hotspots

Summary: The integrated energy station of new energy vehicle hydrogenation/charging/power exchange is proposed, which also includes hydrogen production, hydrogen storage, electricity sales to users and the grid (WPIES). To address the efficiency of renewable energy use, this paper proposes a future value competition strategy for wind and photovoltaic (PV) allocation based on goal optimization (FVCS). In order to better realize the distribution of wind power/PV in the integrated energy station and improve the energy utilization efficiency of the integrated energy station, a two-layer optimization model of FVCS-WPIES is proposed, in which the upper layer model aims to maximize the expected income. The goals of the lower-level model are to maximize total profit, minimize battery losses, and minimize pollutant emissions. The model also considers the hydrogen power constraint and the upper-level model penalty. The comparison results show that the Pareto solution set is superior to the traditional model.

Ru Chen,1,2,* Ming Jiang,1,* Bing Hu,1 Bin Fu,1 Ting Sun1 1Department of Urology, the First Affiliated Hospital of Nanchang University, Nanchang City, People’s Republic of China; 2Department of Urology, the First Hospital of Putian City, Putian City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Fu; Ting Sun, Email urofbin@163.com; 361439919033@email.ncu.edu.cnBackground: Large numbers of studies have identified that procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family members play important roles in tumorigenesis and tumor progression in various cancers. However, the expression pattern, clinical value and function of PLOD family have yet to be analyzed systematically and comprehensively in bladder urothelial carcinoma (BLCA).Methods: We investigated the transcriptional levels, genetic alteration, biological function, immune cell infiltration, data on survival of PLODs in patients with BLCA based on UALCAN, the Cancer Genome Atlas (TCGA) database, Gene Expression Profiling Interactive Analysis (GEPIA), TIMER, STRING, cBioPortal and GSCALite databases. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software using the Cluster Profiler Bioconductor package. Protein–protein interaction (PPI) network was established by STRING and visualized by using R version (3.6.3) software. Survival analysis was performed using the packages “survminer”.Results: The mRNA and protein expression patterns of PLOD family members were noticeably increased in BLC compared with normal tissue. The mRNA expression levels of PLOD1-2 genes were significantly correlated with histological subtypes and PLOD1 was significantly correlated with pathological stage. Furthermore, the high expression levels of PLOD1-2 were remarkably associated with poor overall survival (OS) in BLCA patients, meanwhile high expression levels of PLOD1 and PLOD3 were markedly associated with poor progression-free interval (PFI). In co-expression gene analysis, 50 genes were primarily associated with the differentially expressed PLODs in BLCA. Functional enrichment analysis revealed that protein hydroxylation, collagen fibril organization, and lysine degradation were key biological functions of PLODs in BLCA. Moreover, PLOD family genes were identified as being associated with the activities of tumor-infiltrating immune cells and closely associated with immune responses in BLCA.Conclusion: PLOD family members might serve as potential therapeutic targets and prognostic markers for BLCA patients’ survival.Keywords: bladder cancer, PLODs, immune infiltration, prognosis, biomarker

Zhigang Liu,1,2,* Baisheng Fu,2,* Weicheng Xu,2 Fanxiao Liu,2 Jinlei Dong,2 Lianxin Li,2 Dongsheng Zhou,2 Zhenhai Hao,2 Shun Lu2 1Department of Orthopaedics Surgery, Haining People’s Hospital, Jiaxing, People’s Republic of China; 2Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shun Lu, Department of Orthopaedics Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +8618653189700, Email sdqdpdlushun@163.comPurpose: Traumatic sciatic nerve injury is one of the most serious consequences of acetabular fracture. However, reports on this type of injury are rare. In this study, we investigated the demographics of acetabular fracture with traumatic sciatic nerve injury, the clinical characteristics of patients with these injuries, and potential risk factors.Patients and Methods: We retrospectively reviewed patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of the acetabular fracture, whether or not sciatic nerve injury occurred, types of sciatic nerve injury, and risk factors were analyzed.Results: A total of 195 patients met the diagnostic criteria for acetabular fractures. The average Injury Severity Score was 25.9 and the average Abbreviated Injury Scale score was 12.4. Road traffic accidents and falls from height were the main causes. Chest injuries and lower extremity fractures were the most common associated injuries. Posterior wall fractures were the most common fracture type. After exclusion of spinal cord and iatrogenic sciatic nerve injuries, 18 patients with acetabular fractures had traumatic sciatic nerve injury. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Logistic regression analysis identified a higher AIS score, posterior column fracture, and posterior hip dislocation to be predictors of traumatic sciatic nerve injury.Conclusion: Acetabular fractures were mostly high-energy injuries. Posterior wall fractures were the most common acetabular fracture types. Most patients sustained injury to the sciatic nerve as well as injury to the common peroneal and tibial nerve divisions. A higher AIS score, posterior column fracture, and posterior hip dislocation were predictors of acetabular fracture combined with traumatic sciatic nerve injury.Keywords: acetabular fractures, traumatic sciatic nerve injury, posterior hip dislocation

Lifang Chen,1 Guilan Yu,1 Bo Fu2 1School of Business and Management, Jilin University, Changchun, People’s Republic of China; 2School of Management, Guangzhou University, Guangzhou, People’s Republic of ChinaCorrespondence: Bo Fu, School of Management, Guangzhou University, No. 230 Wai Huan Road West, University City, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 188 0707 1295, Email fubo613@gzhu.edu.cnPurpose: With an increasing demand for shared leadership to address complex, dynamic, and diverse knowledge situations, more attention should be paid to the knowledge behaviors of emergent leaders in teams. However, there is thus far a lack of research into the multilevel nature of shared leadership. Using a dual network lens, this study considers two aspects of shared leadership: “shared leadership as networks” (SLAN) and “shared leadership in networks” (SLIN). Based on emotion appraisal theory, this study investigated the impact of SLIN on leaders’ productive and counterproductive knowledge behaviors through discrete emotions (pride and fear of losing power) and the moderating role of SLAN in guiding their emotions and subsequent behaviors.Methods: A social network approach was employed to obtain data among 431 employees from 72 teams in China. We identified 350 emergent leaders via leadership sociograms. Statistical analysis methods, including multilevel regression analysis, Monte Carlo simulation, and simple slope analysis, were utilized to test our hypotheses.Results: This study indicates that (1) SLIN is positively associated with pride (B = 0.33, p < 0.001), which in turn increases knowledge sharing (B = 0.37, p < 0.001); (2) SLIN is positively related to fear of losing power (B = 0.21, p < 0.05), which in turn is negatively associated with knowledge sharing (B = − 0.23, p < 0.001) and positively associated with knowledge hiding (B = 0.19, p < 0.001); (3) SLAN moderated these aforementioned indirect effects.Conclusion and Originality: First, by defining and differentiating between SLAN and SLIN, this study expands a new perspective on SLIN and facilitates the further development of multilevel shared leadership. Second, this study responds to recent calls for more research on leadership networks and individual-level outcomes of shared leadership. Moreover, it offers a novel theoretical framework to illustrate the impact of SLIN on their knowledge behaviors. Finally, the focus on the moderating role of SLAN identifies a significant contextual factor that prevents the dysfunctional effects of SLIN. These original discoveries enrich the literature on team leadership, emotions, and knowledge management. Further, our novel findings may be of interest to practitioners as they help organizations and teams manage the complex impacts of SLIN on knowledge behaviors in the contexts of an ongoing “affective revolution” and team-based organizational structures.Keywords: shared leadership, pride, fear of losing power, knowledge sharing, knowledge hiding, social network approach

Biqian Fu,&ast; Lin Lu,&ast; Haifu Huang Internal Medicine-Oncology, Shenzhen Hospital of Guangzhou University of Traditional Chinese Medicine, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haifu Huang, Internal Medicine-Oncology, Shenzhen Hospital of Guangzhou University of traditional Chinese Medicine, 6001 North Ring Road, Futian District, Shenzhen, 440300, People’s Republic of China, Tel +0755-83548611, Email huanghaifu2004@163.comPurpose: Lung adenocarcinoma (LUAD) has a high degree of intratumor heterogeneity. Advanced single-cell RNA sequencing (scRNA-seq) technologies have offered tools to analyze intratumor heterogeneity, which improves the accuracy of identifying biomarkers based on single-cell expression data, and thus helps in predicting prognosis of cancer patients and assisting decision-makings for cancer treatment.Patients and Methods: ScRNA-seq data containing two LUAD and two para-cancerous tissue samples were included to identify different cell clusters in tumor tissues. To identify the most relevant modules and important cell subpopulations (clusters) in LUAD tissues, weighted gene co-expression network analysis (WGCNA) was performed. Subsequently, LUAD molecular subtypes were constructed by unsupervised consensus clustering based on genes in key modules. Using differential analysis, univariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic model of LUAD was established.Results: A total of 14 cell clusters belonging to 10 cell types in LUAD were identified. The turquoise module was the most relevant to LUAD among all the modules; cluster 10 (C10, lung epithelial cells) was found to be the most strongly associated with the turquoise module. LUAD samples were divided into two groups of distinct molecular subtypes. Based on the 165 shared genes between the turquoise module and C10, 511 DEGs between the two molecular subtypes were obtained, and five of them were selected to construct the gene signature, which was validated to be an independent prognostic marker of LUAD.Conclusion: Fourteen cell clusters co-existed in LUAD, which contributed to its intratumor heterogeneity. Two molecular subtypes of LUAD were identified and a five-gene signature was developed and validated to be significantly associated with prognostic and clinical characteristics of LUAD patients.Keywords: single-cell RNA sequencing, lung adenocarcinoma, intratumor heterogeneity, molecular subtypes, prognosis, five-gene signature

Ru Chen,1,2,&ast; Bing Hu,1,&ast; Ming Jiang,1,&ast; Wen Deng,1 Ping Zheng,3 Bin Fu1,4 1Department of Urology, the First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Urology, The First Hospital of Putian City, Putian, Fujian, People’s Republic of China; 3Department of Urology, Shangrao municipal Hospital, Shangrao, 334000, Jiangxi Province, People’s Republic of China; 4Jiangxi Institute of Urology, Nanchang City, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu, Email urofbin@163.comObjective: The minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7), which regulates DNA replication and cell cycle progression, is essential for the development and progression of multiple tumors, but their role in bladder cancer development remains unclear. In the present study, the biological role and clinical significance of the MCM complex in bladder cancer were systematically elucidated.Materials and Methods: We analyzed DNA mutations, mRNA expression and protein levels, protein–protein interaction (PPI) networks, functional enrichment, prognostic value of MCM2/3/4/5/6/7 in bladder urothelial carcinoma (BLC) and the connections between the immune cell infiltration and the overall survival of BLC patients with the MCM expression levels using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Cancer Genome Atlas database (TCGA), Human Protein Atlas, UALCAN, STRING, cBioPortal, TIMER and GSCALite databases.Results: The outcomes showed that the mRNA expression level of each member of the MCM complex was significantly correlated with histologic grade and tumor histology in BLC patients. Moreover, survival analysis showed that MCM/2/3/4/5/6/7 mRNA expressions were significantly associated with prognosis in patients with bladder cancer. Moreover, we experimentally validated the overexpression of the MCM2-7 complex in the BLC. Based on functional enrichment and PPI network analysis, the MCM complex might promote the progression of bladder cancer by activating DNA replication and accelerating cell cycle progression. In addition, MCM2/3/4/5/6/7 genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in BLC.Conclusion: Our study suggests that the MCM complex especially MCM2/4/6/7 might be potential molecular therapeutic targets for BLC treatment and might be useful biomarkers for diagnosis and prognosis.Keywords: bladder cancer, minichromosome maintenance complex, bioinformatics, potential biomarkers

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Xiangpeng Zhan, Luyao Chen, Ming Jiang, Bin Fu Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of ChinaCorrespondence: Bin Fu; Luyao Chen, Email urofbin@163.com; chenluyao301@163.comObjective: To construct a prognostic model that estimates the probability of overall survival for T1 high-grade bladder cancer patients after radical cystectomy.Patients and Methods: We enrolled 801 patients diagnosed with T1 high grade and received radical cystectomy from the Surveillance, Epidemiology, and End Results (SEER) database (2004– 2015). All patients were randomly divided into the development group (n = 561) and validation group (n = 240) with the ratio of 7:3. Cox proportional hazards regression analyses were used to filter variables and the Kaplan–Meier method to evaluate survival outcomes. The results of sensitivity analysis determined the variables in the final model. The performance of the model was internally validated by calibration curves, the receiver operating characteristic (ROC) curves, and the concordance index (C-index).Results: The mean survival months were 56.086 in the development group and 58.21 in the validation group. Six variables including age, marital status, tumour size, tumour sites, region nodes examined, and N stage were incorporated in the final nomogram. The accuracy of the nomogram for prediction of overall survival was estimated by C-index (0.732; 0.712– 0.752) and AUC (0.771 for 3-year; 0.766 for 5-year) in the development group. In the validation group, the C-index of the nomogram was 0.752 (0.723– 0.781), and AUC was 0.761 for 3-year as well as 0.793 for 5-year. These results all showed better performance than the AJCC stage. Calibration plots for 3- and 5-year overall survival presented good concordance in both the development and validation group.Conclusion: We have established a prognostic nomogram that provides a more accurate and relevant individualized probability of overall survival for patients with T1HG bladder transitional cell carcinoma after radical cystectomy. It can contribute to improving patient counselling and treatment selection.Keywords: T1 high-grade, SEER, nomogram, prognosis, radical cystectomy, bladder cancer

Ru Chen,1,2,&ast; Zhicheng Zhang,1,&ast; Bing Hu,1,&ast; Ming Jiang,1,&ast; Ping Zheng,3 Wen Deng,1 Bin Fu,1,4 Ting Sun1,4 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, 330000, Jiangxi Province, People’s Republic of China; 2Department of Urology, The First Hospital of Putian City, Putian, 350001, Fujian, People’s Republic of China; 3Department of Urology, Shangrao municipal Hospital, Shangrao, 334000, Jiangxi Province, People’s Republic of China; 4Jiangxi Institute of Urology, Nanchang City, 330000, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu; Ting Sun, Email urofbin@163.com; 361439919033@email.ncu.edu.cnBackground: Multiple studies have identified that E2F transcriptions act as important regulators for the tumorigenesis and progression of several human cancers. However, little is known about the function of E2Fs in clear cell renal cell carcinoma (ccRCC).Methods: We firstly investigated the expression levels, genetic alteration, and biological function of E2Fs in patients with ccRCC and the connections between the immune cell infiltration and the overall survivals of ccRCC patients with the E2Fs expression levels based on UALCAN, The Cancer Genome Atlas database, Gene Expression Profiling Interactive Analysis, TIMER, STRING, GSCALite and cBioPortal databases.Results: Results revealed that the expression levels of E2F1/2/3/4/6/7/8 were markedly upregulated in patients with ccRCC, while the expression of E2F5 displayed an opposite trend. We also experimentally validated the overexpression of E2F3/4/7 in human ccRCC tissues and ccRCC cell lines. Furthermore, the high E2F1/2/3/4/7/8 expression levels were clearly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade. Meanwhile, high expression levels of E2F1/2/4/7/8 were evidently associated with worse overall survivals (OSs) and progression-free survivals (PFSs) of patients harboring ccRCC. Univariate and multivariate analyses illustrated that the expressions of E2F4/5/7 were independent factors associated with the OSs and PFSs of patients with ccRCC. Meanwhile, the mutations in E2Fs were also significantly related to poor OSs and PFSs of patients with ccRCC. Mechanically, the E2Fs genes synergistically promoted the progression of ccRCC by accelerating the cell cycle and inhibiting DNA damage response and apoptosis after performing the protein structure, functional enrichment, and PPI network analyses. In addition, E2Fs genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in ccRCC.Conclusion: As a result, E2F4/7 were highly expressed in ccRCC and significantly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade, tumor immune cell infiltration, and drug sensitivity, consequently translating into poor OSs and PFSs of patients with ccRCC. Our results indicated that E2F4/7 could be potential biomarkers and therapeutic targets of ccRCC patients.Keywords: clear cell renal cell carcinoma, E2Fs, prognosis, UALCAN, GEPIA

Xiaochuan Zhang,1,2,&ast; Fajin Lv,1,&ast; Binjie Fu,1 Wangjia Li,1 Ruiyu Lin,1 Zhigang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Radiology, Chonggang General Hospital, Chongqing, 400080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigang Chu, Tel +86 18723032809, Fax +86 23 68811487, Email chuzg0815@163.comPurpose: To investigate the clinical and computed tomography (CT) characteristics of peripheral small-cell lung cancer (pSCLC) to improve its early diagnosis.Patients and Methods: In total, 70, 132, 69, and 95 patients with pathological confirmed nodular (≤ 3 cm) pSCLC, peripheral non-small cell lung cancer (pNSCLC), benign lung tumor (pBLT), and inflammatory lesion (pIL) were enrolled in this study retrospectively. The clinical and CT data of studied patients with different lesions were analyzed and compared by univariate analysis. Multivariate analysis was used to reveal the key features to distinguish pSCLC from pNSCLC, pBLT, and pIL, respectively.Results: Univariate and multivariate analysis of the clinical and CT characteristics of studied patients indicated that 1) compared with pNSCLC and pIL, vessel convergence, spiculation, and peripheral ground-glass opacity were less common in pSCLC; 2) density homogeneity (OR = 38.84– 120.21, P < 0.05), bronchial cutoff sign (OR = 10.00– 60.13, P = 0.001), hilar lymph node enlargement (OR = 22.81– 95.08, P < 0.0001) (pSCLC vs pNSCLC, pBLT, and pIL), male sex (OR = 5.53– 10.92, P < 0.05) (pSCLC vs pNSCLC and pBLT), and emphysema (OR = 36.57– 56.63, P < 0.05) (pSCLC vs pBLT and pIL) were significantly and independently associated with pSCLC. Type I and II bronchial cutoff sign, especially type I, were closely related to pSCLC.Conclusion: Peripheral solid nodules with homogeneous density, bronchial cutoff sign, hilar lymph node enlargement, but without spiculation or vessel convergence in male patients with emphysema should be highly suspected of pSCLC.Keywords: small-cell lung carcinoma, non-small cell lung carcinoma, tomography, X-ray computed

Bao Fu,1,2,&ast; Hui Feng,1,3,&ast; Fei Gao,1,2 Xiaoyun Fu1,2 1Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, People’s Republic of China; 2Severe Acute Pancreatitis Diagnosis and Treatment Center of Guizhou Province, Zunyi City, Guizhou Province, People’s Republic of China; 3Department of Critical Care Medicine, Renhuai People’s Hospital, Renhuai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun FuDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Dalian Road149, Zunyi City, Guizhou Province, People’s Republic of ChinaTel +8618108522207Fax +8685128608615Email zyyxyfxy@163.comObjective: To observe the relationship between the extrapancreatic necrosis volume and outcomes in patients with severe acute pancreatitis (SAP).Methods: We retrospectively analyzed 125 patients with SAP admitted to Severe Acute Pancreatitis Treatment Center of Guizhou Province from August 2013 to August 2018. All patients had extrapancreatic necrosis. The general clinical data of patients, C-reactive protein (CRP) value within 72 hours of onset, Ranson score, organ failure within 3 days after onset, complications, outcomes, CT severity index (CTSI), extrapancreatic necrosis volume and other information were collected. The correlation between extrapancreatic necrosis volume and hospitalization time, ICU stay, hospitalization cost, and CRP value was analyzed. The incidence of complications was obtained from the electronic medical record system.Results: The mean extrapancreatic necrosis volume was 680 ± 473 mL. The median length of hospital stay was 18.2 (3– 76) days, and the ICU stay was 13.5 (3– 66) days. The extrapancreatic necrosis volume was positively correlated with hospitalization time, ICU stay time, cost of hospitalization and CRP (P < 0.05). The extrapancreatic necrosis volume in organ failure group was significantly higher than that in non-organ failure group (P < 0.05). The extrapancreatic necrosis volume in patients with death was also higher than that in survival (P < 0.05). With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. On the basis of extrapancreatic necrosis volume, the ROC curves yielded an AUC of 0.92 (95% CI: 0.83, 0.99) in predicting the mortality, which was higher than Ranson score (0.90, 95% CI 0.82– 0.96) and CTSI (0.85, 0 95% CI 0.77– 0.91).Conclusion: With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. The extrapancreatic necrosis volume has the potential to be used as a valuable tool to predict the poor outcome of acute pancreatitis.Keywords: acute pancreatitis, acute necrotic collection, CTSI, Ranson score

Wen Deng,1,&ast; Gongxian Wang,1,&ast; Huanhuan Deng,2,&ast; Yan Yan,3,&ast; Ke Zhu,1,&ast; Ru Chen,1,4 Xiaoqiang Liu,1 Luyao Chen,1 Tao Zeng,2 Bin Fu1 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 3Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 4Department of Urology, The First Hospital of Putian City, Putian City, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu; Tao Zeng Tel + 86 13879103861; +86 18779101830Fax +86 0791-88698102; +86 0791-86120120Email urofbin@163.com; taozeng40709@sina.comPurpose: This study aimed to evaluate the functions of critical N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and their correlations with immunotherapeutic targets in clear cell renal cell carcinoma (ccRCC).Methods: m6A-related lncRNAs were analyzed using the dataset from The Cancer Genome Atlas database via Pearson correlation analysis. Then, their prognostic functions in patients with ccRCC were determined via univariate Cox analysis. A prognostic m6A-related lncRNA signature (MRLS) in ccRCC was established using the least absolute shrinkage and selection operator (LASSO) Cox regression model. In addition, the correlations between these prognostic m6A-related lncRNAs with immune checkpoints were further evaluated in clinical samples.Results: MRLS was established by the LASSO Cox regression model on the basis of seven prognostic m6A-related lncRNAs. The risk score for each patient was calculated using the MRLS model, and the patients were further stratified into high- and low-risk subgroups. The MRLS model was validated with a robust prognostic ability by the stratification analysis. On the basis of age, grade, stage, and risk score, a nomogram was developed with a strong reliability in forecasting the overall survival percentages of the patients with ccRCC. Moreover, seven prognostic m6A-related lncRNAs enrolled in the MRLS model were found to be correlated with various immunotherapeutic targets, namely, PD-1, PD-L1, CTLA4, and LAG3, and the expression levels of which in the high-risk subgroup were significantly higher than those in the low-risk subgroup. The significant correlations between LINC00342 and the aforementioned immunotherapeutic targets were also confirmed in clinical samples.Conclusion: In this study, seven m6A-related lncRNAs were identified as potential biomarkers for forecasting the prognosis of patients with ccRCC and evaluating the efficacy of immunotherapy for these patients. Furthermore, a prognostic and predictive MRLS model with a high reliability was constructed to predict the overall survival probability of patients with ccRCC.Keywords: immunotherapy, N6-methyladenosine modification, long non-coding RNA, renal cell carcinoma, prognosis

Lei Zhang, Xuan Liu, Tong Li, Bing Xu, Binfang Fu Department of Neurology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of ChinaCorrespondence: Xuan LiuDepartment of Neurology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of ChinaTel +86 710 3524339Fax +86 710 3524330Email liuxuansk17@hotmail.comPurpose: Selective serotonin reuptake inhibitors (SSRIs) enhance angiogenesis and neurogenesis. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) play an important role in neurogenesis and angiogenesis. However, the effect of SSRIs on cognition and serum BDNF and VEGF in patients with vascular cognitive impairment no dementia (VCIND) is largely unknown.Patients and Methods: It was an open label study. Fifty VCIND patients were randomly allocated to receive fluoxetine (20 mg/d; n = 25) or no fluoxetine (control group; n = 25) for 12 weeks. VCIND patients received fluoxetine 20 mg/d and secondary prevention of stroke for 12 weeks in the fluoxetine group, whereas the control group received only secondary prevention of stroke for 12 weeks. The primary outcome and secondary outcome were of assessment of Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog) score, Ten Point Clock drawing test score (TPC), Verbal Fluency Test (VFT), Trail Making Test form a (TMTa), Trail Making Test form b (TMTb) and Digit Span Test score at baseline and week 12 in the both groups. And serum concentration of BDNF and VEGF was also tested at baseline and week 12 in both groups.Results: After 12 weeks, TPC scores increased more significantly in the fluoxetine group than in the control group, while TMTa score and TMTb score were decreased more significantly in the fluoxetine group than in the control group. We also found that the serum concentration of BDNF and VEGF in the fluoxetine group increased more significantly than in the control group. However, we found no significant differences in mean change from baseline between fluoxetine and control group in ADAS-Cog score, Digit Span Test score and VFT score.Conclusion: Fluoxetine may enhance cognition in certain cognitive domains and serum concentration of BDNF and VEGF in patients with VCIND.Keywords: cognition, enhancement, neuroprotection, selective serotonin reuptake inhibitors

Zhixin Zhang,&ast; Ying Shi,&ast; Haiyan Zheng, Zihuai Zhou, Zhifang Wu, Dongni Shen, Yiru Wang, Yizhou Zhang, Zhe Wang, Baiping Fu Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhe Wang; Baiping Fu Tel +86-571-87217427Fax +86-571-87217427Email 7319012@zju.edu.cn; fbp@zju.edu.cnObjective: This study investigated the effects of mineralizing film consisting of hydroxypropyl methylcellulose (HPMC) and amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs).Material and Methods: The AFCP nanoparticles and mineralizing film were prepared via nanoprecipitation and solvent evaporation, respectively. They were characterized with Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectrometry (ICP-AES), and fluoride ion selective electrode. Thirty-two human enamel slices (4 mm × 4 mm × 1.5 mm) were highly polished and randomly assigned to four groups: negative control (no treatment); pure HPMC film; mineralizing film; GC Tooth Mousse Plus® (contains 10% CPP-ACP and 0.2% NaF). Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, Micro-CT, SEM/EDX, and nanoindentation.Results: The mineralizing film could sustain release of Ca, P and F ions over 24 h and maintain AFCP nanoparticles in metastable state over 8∼ 12 h. During 4 weeks of pH cycling, the mineralizing film group exhibited least color change (∆E), mineral loss and lesion depth (120 ± 10 μm) among four groups (p < 0.05). SEM findings revealed that the porosities among enamel crystals increased in negative control and pure HPMC film groups after pH cycling, whereas in mineralizing film group, the original microstructure of enamel was well conserved and mineral deposits were detected between enamel prisms. Mineralizing film group demonstrated a least reduction of nanomechanical properties such as elastic modulus of 77.02 ± 6.84 GPa and hardness of 3.62 ± 0.57 GPa (p < 0.05).Conclusion: The mineralizing film might be a promising strategy for prevention and management of WSLs via inhibiting enamel demineralization and promoting enamel remineralization.Keywords: mineralizing film, white spot lesions, color, micro-CT, SEM/EDX, nanoindentation

Binjie Fu1 ,* Liangbo Hu2 ,* Fajin Lv,1 Junhao Huang,2 Wangjia Li,1 Yu Ouyang,1 Zhigang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhigang ChuDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86 18723032809Fax +86 23 68811487Email chuzg0815@163.comPurpose: To determine whether new pulmonary lesions will develop in COVID-19 patients with negative initial chest CT findings and to investigate their CT features and outcome during treatment.Patients and Methods: Data were collected retrospectively from 29 patients who had tested positive for COVID-19 by reverse-transcription polymerase chain reaction testing but negative by initial chest CT from January 22 to February 17, 2020. Clinical manifestations, laboratory indicators, and follow-up CT data were evaluated.Results: Among 317 confirmed COVID-19 patients, 29 (9.1%) (mean ± SD, 38.5 ± 20.5 years; 12 women) with negative initial chest CT findings were evaluated. New pulmonary lesions developed in 10 (34.5%) patients on follow-up CT. Mean time from onset of new lesions to initial CT was 5.8 ± 3.0 days (range: 2– 12 days). New lesions (mean involved lobes and segments: 2.5 ± 1.6 [range: 1– 5] and 4.5 ± 4.5 [range: 1– 13]) were mainly spherical/patchy ground-glass opacities frequently located in the left lower lobe (9, 90.0%). Among the 10 patients, lesions in 6 (60.0%) indicated progression after occurrence, and those in 10 (100.0%) indicated significant absorption on latest CT. When new lesions developed, 6 (60.0%) patients developed new symptoms or had aggravated symptoms and 3 (30.0%) had decreased lymphocyte count. Patients with worsening symptoms had higher involvement of lung segments (mean: 6.5 ± 5.0, range: 1– 13) than asymptomatic patients (mean: 1.5 ± 0.6, range: 1– 2) (P = 0.057).Conclusion: In COVID-19 patients with negative initial chest CT findings, new pulmonary lesions may develop during treatment. Repeat CT is necessary for monitoring the disease, especially when patients have worsening symptoms or laboratory indicators.Keywords: coronavirus disease 2019, SARS-CoV-2, follow-up, CT imaging

Junwen Pei, Binfan Fu, Lifeng Jiang, Taizhen Sun Department of Integrated Traditional Chinese and Western Medicine, The Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China Background: Tremendous growth in nanotechnology has opened up new frontiers in fundamental and applied aspects, including the synthesis of nanoscale matter and understanding/utilizing its exotic physicochemical and optoelectronic properties. Green-synthesis methods employing either biological microorganisms or plant extracts have emerged as a simple and alternative to chemical synthesis. Methods: In our present study, we aimed to synthesize silver nanoparticles (AgNPs) in combination with an aqueous extract of Coptis chinensis (CC) using a suitable ecofriendly green-synthesis way. Results: In our results, ultraviolet-visible spectroscopy revealed a near-absorbance peak at 450 nm, which confirmed the AgNP synthesis. The crystalline nature of the AgNPs was revealed with X-ray diffraction. Transmission electron-microscopy analysis showed spherically dispersed nanoparticles of 6–45 nm diameter. We analyzed the elementary mechanism across A549 lung carcinoma cells ahead of treatment with doses of CC-AgNPs (10 µg/mL and 25 µg/mL). The antiproliferative effect of CC-AgNPs revealed a significant decline in cell viability. Antibacterial assays with both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria exhibited a higher zone of inhibition against S. aureus. Conclusion: Furthermore, CC-AgNPs regulated apoptosis using the intrinsic pathway to inhibit A549-cell proliferation. Proliferation migration and invasion were notably inhibited by CC-AgNPs, which promoted apoptosis in lung adenocarcinoma cells by regulating the apoptotic pathway. Keywords: Coptis chinensis, silver nanoparticles, antimicrobial, lung cancer, apoptosis, invasion

Bo Fu,1 Shao-Nan Wen,1 Bin Wang,1 Kun Wang,2 Ji-Yan Zhang,3 Xie-Chuan Weng,1 Shao-Jun Liu1 1State Key Laboratory of Proteomics, Department of Neurobiology, Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China; 2Department of Occupational Medicine, Tianjin Institute of Environmental and Occupational Medicine, Tianjin 300050, China; 3Department of Molecular Immunology, Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China Purpose: Ventral tegmental area (VTA) dopamine system plays an important role in depression and is also involved in pain experience. In this study, we investigated the VTA dopaminergic (DA) neuron firing and local field potential (LFP) in pain-related depression, and we try to explore the underlying relationship between pain and depression.Materials and methods: We used neuropathic pain model [spare nerve injury (SNI)] to induce pain-related depression. The Dixon up–down method was used to test mechanical hypersensitivity. Behavioral changes like open field test, sucrose preference test, and forced swim test were used to test depression-like behaviors. Gabapentin (GBP) was used to explore the chronic analgesic treatment that could reverse pain-related depression. To investigate the in vivo variations of VTA DA neuron firing and LFP, multichannel acquisition processor system was used.Results: We used SNI to induce depression-like behaviors. Repeated GBP treatment reversed these behaviors after 14 days of injection. An in vivo electrophysiological analysis of the firing characteristics of VTA DA neurons and LFP revealed that SNI increased the firing rate of DA neurons, but not the burst firing activity. Surprisingly, chronic GBP reversed the firing rate of DA neurons and reduced the burst firing activity. Moreover, SNI increased the LFP power in delta and theta oscillation and decreased it in beta oscillation. Repeated administration of GBP significantly suppressed theta oscillation. Above all, chronic GBP altered these characteristics to reverse depression-like behaviors.Conclusion: The present study confirmed that the tonic firing activity of VTA DA neurons, but not the burst firing activity, was the key factor in peripheral neuropathy–induced depression. Chronic GBP regulated the firing pattern of DA neurons and decreased theta oscillation in VTA to treat pain-related depression. This variation tendency of electrophysiological characteristics of VTA DA neurons and theta oscillation in VTA might represent an attempt to cope with pain-related negative mood disorder. Keywords: chronic neuropathic pain, depression, dopaminergic neuron, LFP, VTA