Search

Pengfeng Gong,1,&ast; Jie Shen,1 Yu Yang,2,&ast; Dong Xue,1 Hao Lu,1 Qianfeng Zhuang,1 Xiaogang Wang,1 Zinong Tian,1 Yiming Chen,1 Cheng Chen,1 Yunjie Cao1 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China; 2Department of Hepato-Pancreato-Biliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjie Cao, Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China, Tel +86-13775188220, Email caoyunjie1847@163.comObjective: To explore patients’ knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP.Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other.Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤ 30, 31– 40, and > 40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15– 22) vs 0 (0– 6), P< 0.001), attitude (26 (24– 26) vs 14 (10– 18), P< 0.001), and practice (20 (17– 24) vs 8 (6– 16), P< 0.001) than those who did not. A higher proportion of patients with varicocelectomy were < 40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P< 0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P< 0.001). Knowledge, college/bachelor’s degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P< 0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P< 0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy.Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.Keywords: knowledge, attitude, practice, varicocele, varicocelectomy, cross-sectional study

Qiwen Yang,1,2,&ast; Tairan Dong,1,&ast; Diyang Lyu,2 Donghua Xue,1,2 Rui Zhuang,2 Liyong Ma,2 Lijing Zhang2 1Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijing Zhang, Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email dzmyyccu@163.comBackground & Objective: Anemia in patients with heart failure (HF) is a growing concern. However, there has no bibliometric analysis in this area up to now. The aim of this study is to explore the status and trends in the field of anemia in HF through the bibliometric analysis, and to provide an outlook on future research.Methods: We retrieved publications from the Web of Science Core Collection database, and the following data analysis and visualization tools were utilized to perform data processing, statistical computing and graphics generation: VOSviewer (v.1.6.18), CiteSpace (v.6.2 R5), Scimago Graphica (v.1.0.36), Biblimatrix and Microsoft Excel.Results: We identified a total of 3490 publications from 2004 to 2023. The publications in the field of anemia in HF are growing steadily. The United States, the United Kingdom, and Italy were the leading countries in this area. Stefan D Anker, as the most influential author, held the most total citations and publications. Harvard University was the most productive institution in this area. The European Journal of Heart Failure had published the most papers. Through the analysis of co-citations, 14 major clusters based on cluster labels were identified. Keyword analysis showed that mortality, outcome, prevalence, and risk were the most frequent keywords, and the potential research hotspots in the future will be intravenous iron and iron deficiency.Conclusion: This study provides a comprehensive analysis of countries, authors, institutions, journals, co-cited references, and keywords in the field of anemia in HF through bibliometric analysis and data visualization. The status, hotspots and future trends in this field offer a reference for in-depth research. Further studies are necessary in the future to broaden the spectrum of research in this field, to evaluate comprehensive approaches to treating anemia in patients with HF, and to find rational targets for the management of anemia.Keywords: anemia, heart failure, hemoglobin, iron deficiency, bibliometrics

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

Ling Zhou,1,&ast; Yu Gan,1,&ast; Yanjun Wu,1 Dongdong Xue,1 Jianhong Hu,1 Yilan Zhang,2 Yang Liu,3 Siyuan Ma,1 Junyi Zhou,1 Gaoxing Luo,1 Daizhi Peng,1 Wei Qian1 1Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China; 2Department of Oral and Maxillofacial Head and Neck Surgery, Army Medical Center of PLA/Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China; 3Department of Urology, Urology Institute of PLA, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daizhi Peng; Wei Qian, Email dzpengpub@126.com; weiqian87@126.comIntroduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC).Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision.Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified.Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.Keywords: indocyanine green, ICG, near-infrared fluorescence imaging, skin squamous cell carcinoma, biopsy, radical resection

Danni Xue,1,&ast; Binghai Sun,1,&ast; Weijian Li,1 Hui Zhou,2 Fujun Ding,1 Weilong Xiao1,3 1School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China; 2Jinhua Advanced Research Institute, Jinhua, Zhejiang, 321004, People’s Republic of China; 3Research Unit Occupational & Organizational Psychology and Professional Learning, KU Leuven, Leuven, 3000, Belgium&ast;These authors contributed equally to this workCorrespondence: Fujun Ding, School of Psychology, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, People’s Republic of China, Email dfj201810100017@163.comBackground: Teacher burnout is characterized by emotional and physical exhaustion resulting from excessive work-related stress. Previous research based on traditional latent variable theory has revealed a significant negative relationship between TB and psychological capital (PsyCap). This study explored the complex symptoms of TB and the contact points of PsyCap in reducing TB using psychometric network analysis.Methods: A total of 3991 teachers completed the burnout subscale of the Professional Quality of Life and Psychological Capital Scale.Results: The results showed that: (a) In the TB network, the core symptoms displayed by teachers due to burnout are difficulty feeling “I am a very caring person”, “I am happy”, and “I am the person I always wanted to be”; (b) The TB-PsyCap network was closely connected, and the symptoms affected each other. PsyCap affected the TB network through “I feel optimistic and happy almost every day” and “I often feel that there is a future as a teacher”; (c) PsyCap’s bridge symptoms had a negative impact on TB, and PsyCap may reduce TB primarily through optimistic, hopeful dimensions.Conclusion and Implications: Psychometric network analysis helps us understand the complex symptoms of TB and the contact points of PsyCap in reducing TB. This study offers valuable insights into the prevention of, and intervention in, burnout within the teaching community.Keywords: teacher burnout, psychological capital, network analysis, network comparison

Wenli Hui, Wenhua Mu, Cong Zhao, Dan Xue, Zihua Zhong, Yani Fang, Ming Gao, Xiao Li, Shihao Gao, Kaiyue Liu, Kunping Yan College of Life Science, Northwest University, Xi’an City, Shaanxi Province, 710069, People’s Republic of ChinaCorrespondence: Kunping Yan, Email kpyan@nwu.edu.cnIntroduction: A limitation of hemoglobin-based oxygen carriers (HBOCs) as oxygen therapeutics is unpolymerized hemoglobin, which induces vasoconstriction leading to hypertension. The removal of unpolymerized hemoglobin from polymerized hemoglobin (PolyHb) is complex, expensive, and time-consuming.Methods: Herein, we developed a method to completely polymerize hemoglobin almost without unpolymerized hemoglobin. Hemoglobin was adsorbed on the anion-exchange resin Q Sepharose Fast Flow or DEAE Sepharose Fast Flow, and acetal, a crosslinker prepared from glutaraldehyde and ethylene glycol, was employed to polymerize the hemoglobin. The polymerization conditions, including reaction time, pH, resin type, and molar ratios of glutaraldehyde to ethylene glycol and hemoglobin to acetal, were optimized. The blood pressure and blood gas of mice injected with PolyHb were monitored as well.Results: The optimal polymerization condition of PolyHb was when the molar ratio of glutaraldehyde to ethylene glycol was 1:20, and the molar ratio of 10 mg/mL hemoglobin adsorbed on anion-exchange resin to glutaraldehyde was 1:300 for 60 min. Under optimized reactive conditions, hemoglobin was almost completely polymerized, with < 1% hemoglobin remaining unpolymerized, and the molecular weight of PolyHb was more centrally distributed. Furthermore, hypertension was not induced in mice by PolyHb, and there were also no pathological changes observed in arterial oxygen, blood gas, electrolytes, and some metabolic indicators.Conclusion: The findings of this study indicate that the use of solid-phase polymerization and acetal is a highly effective and innovative approach to HBOCs, resulting in the almost completely polymerized hemoglobin. These results offer promising implications for the development of new methods for preparing HBOCs.Graphical Abstract: Keywords: polymerized hemoglobin, glutaraldehyde, acetal, solid-phase adsorption, hemoglobin-based oxygen carriers, HBOCs

Pengfei Wang,1,2,&ast; Xuxu Liu,1,2,&ast; Jingjing Yu,1,2 Ziang Meng,1,2 Zhenyi Lv,1,2 Ce Shang,1,2 Qi Geng,1,2 Dawei Wang,1,2 Dongbo Xue,1,2 Long Li3 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dawei Wang, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, People’s Republic of China, Tel/Fax +86 451 85555776, Email daweixxx2001@163.com Long Li, Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People’s Hospital, Tenth People’s Hospital of Tongji University, 301 Yanchang Middle Road, Shanghai, 200072, People’s Republic of China, Tel/Fax +86 21 66307011, Email ll007@hrbmu.edu.cnPurpose: Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated mortality worldwide. Fucosyltransferases (FUTs) are associated with numerous cancers. We aimed to investigate the functions of FUTs in COAD.Patients and Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the expression and clinical relevance of FUTs in COAD. Real Time Quantitative PCR (RT-qPCR), Western blot, immunohistochemistry and ELISA were used to detect the relative RNA and protein expression levels. Colitis-associated cancer mice treated with Fusobacterium nucleatum were used to illustrate the effects of Fusobacterium nucleatum on FUTs and COAD. Luciferase reporting assay was used to investigate the binding of miRNA to mRNA.Results: TCGA and GEO datasets showed abnormal expression of FUTs in COAD at transcript level. RT-qPCR, Western blot and immunohistochemistry showed increased expression of FUT1, POFUT1 and POFUT2 in COAD. COAD patients with a high expression of FUT1, FUT11, FUT13 (POFUT2) had a worse prognosis, while patients with a high expression of FUT2, FUT3, FUT6 had a better prognosis. FUT1 and POFUT2 could independently predict the prognosis of COAD patients. Functional analysis by CancerSEA database showed that FUT3, FUT6, FUT8, FUT12 (POFUT1) and FUT13 are associated with differentiation, apoptosis, invasion, quiescence, and hypoxia. FUTs are associated with the tumor microenvironment of COAD. FUT1 regulated by miR-939-3p inhibit the expression of MUC2. Fusobacterium nucleatum may affect the expression of FUTs by affecting their transcription factors and miRNA levels. Moreover, Fusobacterium nucleatum promotes COAD progression through the miR-939-3p/FUT1/MUC2 axis.Conclusion: Fucosyltransferases play an important role and may be the mediator of Fusobacterium nucleatum promoting COAD progression.Keywords: fucosyltransferases, prognostic, oncological properties, Fusobacterium nucleatum, colon adenocarcinoma

Dongdong Xue,1 Jingzhao Han,1 Ze Liang,1 Lin Jia,1 Yifan Liu,1,2 Hongfang Tuo,1 Yanhui Peng1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Department of Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanhui Peng, Department of Hepatobiliary Surgery, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang, 050051, Hebei Province, People’s Republic of China, Tel/Fax +86-311-859 8321, Email yhpeng@hebmu.edu.cnAbstract: As a common malignant tumor worldwide, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory, even though treatment methods have improved. Despite the developments in traditional chemotherapy and emerging targeted immunotherapy, the problem of recurrence and metastasis of HCC and adverse effects on survival and prognosis are still serious. Drug resistance is a daunting challenge that impedes HCC treatment. Exosomes, a class of extracellular vesicles ranging in size from 30 to 100 nm, have been the focus of recent studies. Exosomes can activate various signaling pathways and regulate the tumor microenvironment with their cargo, which includes functional lipids, proteins, and nucleic acids. Thus, they change the phenotype of recipient cells via exosome-mediated communication. Exosomes secreted by tumors or stromal cells can also transfer drug-resistant traits to other tumor cells. However, their effects on drug resistance in HCC are not completely understood. In this review, we summarize and discuss the underlying relationship between exosomes and drug resistance in HCC. In addition, we also show that exosomes may act as candidate biomarkers for predicting and monitoring drug responses and as potential targets or vectors to reverse the drug resistance of HCC.Keywords: hepatocellular carcinoma, exosome, tumor microenvironment, targeted therapy

Xinyang Wang,1,&ast; Dandan Xue,1,&ast; Xiaoxia Zhu,2,&ast; Rui Geng,3 Xin Bao,2 Xiang Chen,2 Tiansong Xia1,4 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Thyroid and Breast, Yixing People’s Hospital Affiliated to Jiangsu University, Yixing, People’s Republic of China; 3Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 4Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang ChenDepartment of Thyroid and Breast, Yixing People’s Hospital Affiliated to Jiangsu University, 75 Zhen’guan Road, Yixing, 214200, People’s Republic of ChinaEmail staff984@yxph.comTiansong XiaDepartment of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of ChinaEmail xiatsswms@163.comPurpose: Breast cancer accounts for the highest incidence of tumors in women. Immune infiltrating of the tumor microenvironment positively correlates with the overall survival of breast cancer patients. PLAT can affect the development of many cancers, but its mechanism in breast cancer is unclear. We assessed the correlation between PLAT and immune infiltrating in breast cancer based on the TCGA database.Patients and Methods: The expression and DNA methylation of PLAT in breast cancer with different clinical characteristics was tested by Wilcoxon signed rank test and displayed by box plot. Sequentially, Kaplan–Meier plot was employed to compare the difference in overall survival rates between patients with different expressed levels. Univariate and multivariate Cox regression analyses were used to validate whether PLAT is an independent prognostic factor of breast cancer. After that, GO, KEGG, and gene-set enrichment analysis were employed to do functional enrichment analysis. Finally, TIMER, TISIDB database, and ssGSEA algorithm were used to assess the correlation between PLAT expression and various immune characteristics. The correlation between PLAT expression and DNA methylation was examined by Pearson correlation coefficient.Results: PLAT displays differential expression levels in breast cancer patients with various clinical characteristics. As an independent protective factor for breast cancer, PLAT may significantly correlate with the immune status of breast cancer by adjusting many immune molecules and affecting the immune infiltration in the tumor microenvironment. DNA methylation of PLAT downregulates the gene expression and affects the prognosis of breast cancer.Conclusion: PLAT can be considered a potential biomarker to predict breast cancer prognosis and might contribute to the development of immunological treatment strategies.Keywords: tPA, prognosis, immune infiltration, bioinformatic

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pulmonary arterial pressure and organized thrombi within pulmonary arteries. Riociguat is a soluble guanylate cyclase stimulator and is approved for patients with inoperable CTEPH or residual pulmonary hypertension after pulmonary endarterectomy (PEA). Previous work suggested that riociguat treatment is associated with an increased risk of bleeding, although the mechanism is unclear. The aim of this study is to assess how riociguat affects primary hemostasis by studying its effect on the interaction between platelets and endothelial cells derived from CTEPH patients. Pulmonary artery endothelial cells (PAECs) were isolated from thrombus‐free regions of PEA material. Purified PAECs were cultured in flow chambers and were stimulated with 0.1 and 1 µM riociguat for 24 h before flow experiments. After stimulation with histamine, PAECs were exposed to platelets under shear stress. Platelet adhesion and expression of von Willebrand Factor (VWF) were evaluated to assess the role of riociguat in hemostasis. Under dynamic conditions, 0.1 and 1.0 µM of riociguat suppressed platelet adhesion on the surface of PAECs. Although riociguat did not affect intracellular expression and secretion of VWF, PAECs stimulated with riociguat produced fewer VWF strings than unstimulated PAECs. Flow cytometry suggested that decreased VWF string formation upon riociguat treatment may be associated with suppressed cell surface expression of P‐selectin, a protein that stabilizes VWF anchoring on the endothelial surface. In conclusion, Riociguat inhibits VWF string elongation and platelet adhesion on the surface of CTEPH‐PAECs, possibly by reduced P‐selectin cell surface expression.

Yu Yang,1 Pengfeng Gong,2 Dongwei Yao,3 Dong Xue,2 Xiaozhou He2 1Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Urology, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaozhou HeDepartment of Urology, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Road, Changzhou, 213000, People’s Republic of ChinaTel +86-519-68873211Email xiaozhouhe59@163.comBackground: Long noncoding RNAs (lncRNAs) have been regarded as crucial regulators in many cancers, including clear cell renal cell carcinoma (ccRCC). This research aimed to explore the biological role and molecular mechanism of lncRNA HCG18 in ccRCC.Materials and Methods: The expression levels of HCG18, miR-152-3p and RAB14 were examined by RT-qPCR. Cell viability, migration and invasion were examined by CCK-8 and transwell assays. Luciferase reporter and RIP assays were adopted to verify the interaction between miR-152-3p and HCG18 or RAB14.Results: It was found that HCG18 expression was highly expressed in ccRCC tissues and cells, and patients with high expression of HCG18 had a short overall survival time. Moreover, HCG18 depletion attenuated ccRCC cell viability, migration and invasion. In addition, miR-152-3p was confirmed as a downstream target of HCG18 and was inversely regulated by HCG18, and RAB14 was a target of miR-152-3p. Functional assays demonstrated that miR-152-3p silencing or RAB14 addition abolished the inhibitory effects of HCG18 knockdown on ccRCC progression.Conclusion: The results of the present study indicated that HCG18 accelerated the development and progression of ccRCC by upregulating RAB14 via sponging miR-152-3p, suggesting a potential therapeutic target for patients with ccRCC.Keywords: HCG18, miR-152-3p, RAB14, clear cell renal cell carcinoma

Qiang Wang,* Hao Wang,* Qingxu Jing, Yang Yang, Dongbo Xue, Chenjun Hao, Weihui Zhang Department of General Surgery, Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongbo Xue; Chenjun HaoDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical University, Youzheng Street 23, Harbin, 150001, People’s Republic of ChinaEmail xuedongbo@hrbmu.edu.cn; haochenjun1986@163.comIntroduction: As endogenous miRNA carriers, exosomes play a role in the pathophysiological processes of various diseases. However, their functions and regulation mechanisms in pancreatic fibrosis remain unclear.Methods: In this study, an RNA microarray was used to detect differentially expressed exosomal miR-130a-3p in AR42J cells before and after taurolithocholate (TLC) treatment. mRNA-seq was used to screen differentially expressed genes before and after pancreatic stellate cell (PSC) activation. We used the STRING database to construct a protein-protein interaction (PPI) network for differentially expressed genes, used CytoNCA to analyze the centrality of the PPI network, and identified 10 essential proteins in the biological network. Then, the TargetScan and miRanda databases were used to predict the target genes of miR-130a-3p. The intersections of the target genes and the mRNAs encoding the 10 essential proteins were identified to construct miR-130a-3p/peroxisome proliferator-activated receptor gamma (PPAR-γ) pairs. Fluorescence labeling of exosomes and dynamic tracing showed that exosomes can fuse with the cell membranes of PSCs and transport miR-130a-3p into PSCs. A luciferase reporter gene assay was used to confirm that miR-130a-3p can bind to PPAR-γ to inhibit PPAR-γ expression. In vitro and in vivo functional experiments were performed for gain-of-function studies and loss-of-function studies, respectively.Results: The studies showed that acinar cell-derived exosomal miR-130a-3p promotes PSC activation and collagen formation through targeting of stellate cellular PPAR-γ. Knockdown of miR-130a-3p significantly improved pancreatic fibrosis. Notably, miR-130a-3p knockdown reduced serum levels of hyaluronic acid (HA) and β-amylase and increased the C-peptide level to protect endocrine and exocrine pancreatic functions and the function of endothelial cells.Conclusion: This study revealed that the exosomal miR-130a-3p/PPAR-γ axis participates in PSC activation and the mechanism of chronic pancreatitis (CP) with fibrosis, thus providing a potential new target for the treatment of chronic pancreatic fibrosis.Keywords: pancreatitis, exosomes, miR-130a-3p, pancreatic fibrosis, PPAR-γ

Li Li,1,2 Yajing Chen,1 Gaixia Xu,2,3 Dongmeng Liu,1 Zhiwen Yang,1 Tingting Chen,1 Xiaomei Wang,1 Wenxiao Jiang,1 Dahui Xue,1 Guimiao Lin1 1Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Shenzhen Key Laboratory of Synthetic Biology, Department of Physiology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, People’s Republic of China; 2Key Laboratory of Optoelectronics Devices and Systems of Ministry of Education/Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518055, People’s Republic of ChinaCorrespondence: Guimiao LinSchool of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen 518060, People’s Republic of ChinaTel/ Fax +86-755-86671903Email gmlin@szu.edu.cnIntroduction: Indium phosphide (InP) quantum dots (QDs) have shown a broad application prospect in the fields of biophotonics and nanomedicine. However, the potential toxicity of InP QDs has not been systematically evaluated. In particular, the effects of different surface modifications on the biodistribution and toxicity of InP QDs are still unknown, which hinders their further developments. The present study aims to investigate the biodistribution and in vivo toxicity of InP/ZnS QDs.Methods: Three kinds of InP/ZnS QDs with different surface modifications, hQDs (QDs-OH), aQDs (QDs-NH2), and cQDs (QDs-COOH) were intravenously injected into BALB/c mice at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively. Biodistribution of three QDs was determined through cryosection fluorescence microscopy and ICP-MS analysis. The subsequent effects of InP/ZnS QDs on histopathology, hematology and blood biochemistry were evaluated at 1, 3, 7, 14 and 28 days post-injection.Results: These types of InP/ZnS QDs were rapidly distributed in the major organs of mice, mainly in the liver and spleen, and lasted for 28 days. No abnormal behavior, weight change or organ index were observed during the whole observation period, except that 2 mice died on Day 1 after 25 mg/kg BW hQDs treatment. The results of H&E staining showed that no obvious histopathological abnormalities were observed in the main organs (including heart, liver, spleen, lung, kidney, and brain) of all mice injected with different surface-functionalized QDs. Low concentration exposure of three QDs hardly caused obvious toxicity, while high concentration exposure of the three QDs could cause some changes in hematological parameters or biochemical parameters related to liver function or cardiac function. More attention needs to be paid on cQDs as high-dose exposure of cQDs induced death, acute inflammatory reaction and slight changes in liver function in mice.Conclusion: The surface modification and exposure dose can influence the biological behavior and in vivo toxicity of QDs. The surface chemistry should be fully considered in the design of InP-based QDs for their biomedical applications.Keywords: InP/ZnS quantum dots, surface chemistry, in vivo, biodistribution, nanotoxicology

Pancreatic Ductal Adenocarcinoma (PDAC) is among the most aggressive human cancers and occurs globally at an increasing incidence. Metastases are the primary cause of cancer-related death and, in the majority of cases, PDAC is accompanied by metastatic disease at the time of diagnosis, making it a particularly lethal cancer. Regrettably, to date, no curative treatment has been developed for patients with metastatic disease, resulting in a 5-year survival rate of only 11%. We previously found that the protein expression of the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBPδ) negatively correlates with lymph node involvement in PDAC patients. To better comprehend the etiology of metastatic PDAC, we explored the role of C/EBPδ at different steps of the metastatic cascade, using established in vitro models. We found that C/EBPδ has a major impact on cell motility, an important prerequisite for tumor cells to leave the primary tumor and to reach distant sites. Our data suggest that C/EBPδ induces downstream pathways that modulate actin cytoskeleton dynamics to reduce cell migration and to induce a more epithelial-like cellular phenotype. Understanding the mechanisms dictating epithelial and mesenchymal features holds great promise for improving the treatment of PDAC.

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

Deting Xue,1,* Erman Chen,1,* Huiming Zhong,2,* Wei Zhang,1 Shengdong Wang,1 Muhammad Umar Joomun,1 Tianyi Yao,3 Yanbin Tan,1 ShiSheng Lin,3 Qiang Zheng,1 Zhijun Pan1 1Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 3Department of Information Science and Electronic Engineering and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, People’s Republic of China *These authors contributed equally to this work Background: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. Materials and methods: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi­gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. Results: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. Conclusion: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering. Keywords: graphene oxide, osteo-immunomodulatory, bone marrow mesenchymal stem cells, osteogenesis, angiogenesis, RAW264.7 cells, HUVECs

Liming Dong,1 Honglin Ding,2 Yanpei Li,1 Dongwei Xue,1 Yili Liu1 1Department of Urology, The Fourth Affiliated Hospital of China Medical University, Liaoning 110000, Shenyang, China; 2Department of Urology, The Affiliated Hospital of Chifeng Medical College, Chifeng 024000, Inner Mongolia, China Introduction: Terminal differentiation-induced non-coding RNA (TINCR) has been suggested to have aberrant expression in multiple human cancers, and functions as tumor suppressor or promoter in various types of human tumors depending on the specific cancer types. The expression status and biological function of TINCR in prostate cancer is still unknown. Materials and methods: In our study, we detected TINCR expression in prostate cancer tissue samples and cell lines, and analyzed the association between TINCR expression and clinical parameters in 160 prostate cancer patients. Moreover, we conducted gain-of-function and loss-of-function studies in prostate cancer cell to explore the biological function and molecular mechanism of TINCR. Results: In our results, low-expression TINCR was observed in prostate cancer, and correlated with advanced clinical T stage, lymph node involvement, distant metastasis, high Gleason score and poor prognosis in prostate cancer patients. Moreover, levels of TINCR expression were negatively associated with TRIP13 mRNA and protein expressions in prostate cancer tissues, and negatively regulated the TRIP13 mRNA and protein expressions in prostate cancer cell lines. TINCR inhibits prostate cancer cell proliferation, migration and invasion via suppressing TRIP13 expression. Conclusion: TINCR plays a tumor suppressive role in regulating prostate cancer cell proliferation, migration and invasion through modulating TRIP13 expression. Keywords: lncRNA, TINCR, biomarker, TRIP13, prostate cancer

Pulmonary arterial hypertension (PAH) patients eventually die of right heart failure (RHF). Currently, there is no suitable pre-clinical model to study PAH. Therefore, we aim to develop a right heart dysfunction (RHD) model using the 3-dimensional engineered heart tissue (EHT) approach and cardiomyocytes derived from patient-induced pluripotent stem cells (iPSCs) to unravel the mechanisms that determine the fate of a pressure-overloaded right ventricle. iPSCs from PAH and healthy control subjects were differentiated into cardiomyocytes (iPSC-CMs), incorporated into the EHT, and maintained for 28 days. In comparison with control iPSC-CMs, PAH-derived iPSC-CMs exhibited decreased beating frequency and increased contraction and relaxation times. iPSC-CM alignment within the EHT was observed. PAH-derived EHTs exhibited higher force, and contraction and relaxation times compared with control EHTs. Increased afterload was induced using 2× stiffer posts from day 0. Due to high variability, there were no functional differences between normal and stiffer EHTs, and no differences in the hypertrophic gene expression. In conclusion, under baseline spontaneous conditions, PAH-derived iPSC-CMs and EHTs show prolonged contraction compared with controls, as observed clinically in PAH patients. Further optimization of the hypertrophic model and profound characterization may provide a platform for disease modelling and drug screening.

Numerous functional studies have shown that nitrergic neurotransmission plays a central role in peristalsis and sphincter relaxation throughout the gut and impaired nitrergic neurotransmission has been implicated in clinical disorders of all parts of the gut. However, the role of nitric oxide (NO) as a neurotransmitter continues to be controversial because: 1) the cellular site of production during neurotransmission is not well established; 2) NO may interacts with other inhibitory neurotransmitter candidates, making it difficult to understand its precise role.Imaging NO can help resolve many of the controversies regarding the role of NO in nitrergic neurotransmission. Imaging of NO and its cellular site of production is now possible. NO forms quantifiable fluorescent compound with diaminofluorescein (DAF) and allows imaging of NO with good specificity and sensitivity in living cells. In this report we describe visualization and regulation of NO and calcium (Ca(2+)) in the myenteric nerve varicosities during neurotransmission using multiphoton microscopy. Our results in mice gastric muscle strips provide visual proof that NO is produced de novo in the nitrergic nerve varicosities upon nonadrenergic noncholinergic (NANC) nerve stimulation. These studies show that NO is a neurotransmitter rather than a mediator. Changes in NO production in response to various pharmacological treatments correlated well with changes in slow inhibitory junction potential of smooth muscles.Dual imaging and electrophysiologic studies provide visual proof that during nitrergic neurotransmission NO is produced in the nerve terminals. Such studies may help define whether NO production or its signaling pathway is responsible for impaired nitrergic neurotransmission in pathological states.

China has to perform high-intensity and high-chemical input agricultural production to improve its food security, which has caused uncertainty in the development of ecological agriculture. This study utilizes bibliometrics and spatial statistical methods to examine the representative literature on ecological agriculture published in the CNKI database from 2012 to 2023. The findings reveal that keywords such as rural revitalization, modern agriculture, and ecological tourism are frequently mentioned while emerging interests include carbon neutrality, eco-circular agriculture, and industrial integration. The main clusters of keywords can be classified into specific practical research, general studies, and countermeasures orderly. The themes of ecological tourism, developing mode, and rural revitalization have attracted long-lasting concerns in research over the past decade. Spatial statistical analysis indicates that, aside from the Eastern coastal areas, most provinces in China exhibit insufficient collaboration and limited spill-over effects in research of ecological agriculture, highlighting the necessity for enhanced integration. This study also provides recommendations to address the prevailing challenges to food security through the promotion of ecological agriculture in China. [ABSTRACT FROM AUTHOR]