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Yang Li,1,* Huihui Fan,2,* Wei Wei,3 Hanyu Zhu,4 Haifeng Wang,4 Dayao Lyu,1 Zengrui Zhang,1 Ying Tan1 1Department of Neurology, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, People’s Republic of China; 2Department of Ultrasound, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, People’s Republic of China; 3Department of Key Laboratory of Basic Research and Clinical Translation, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, People’s Republic of China; 4Department of Neurology, Medical School of Huzhou University, Huzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Tan, Email zzftyzhy@126.comIntroduction: The primary clinical manifestation of venous thrombosis is discomfort in the lower extremities. Some early Parkinson’s disease (PD) patients feel discomfort in the lower limbs. Venous thrombosis can risk lives by causing pulmonary embolism. This study examines the incidence of DVT in early PD patients and its correlation with different clinical and lab features.Methods: A cross-sectional study was conducted on 117 patients with early-stage PD. Ultrasonography was employed to detect the presence of DVT. Factors such as age, gender, body mass index, lifestyle habits (smoking and drinking), medical history (hypertension, diabetes, atrial fibrillation, and tumor), and other lab tests linked to thrombosis were analyzed.Results: In 117 patients, 11 (9.4%) had DVT, while 106 (90.6%) did not. There were no significant differences in gender, BMI, habits, medical history, or other thrombosis-related tests between both groups. However, DVT patients were older with higher d-dimer levels. They also showed an increased right substantia nigra ultrasound echo area, higher HY grades, higher UPDRS 3 scores, less improvement in UPDRS 3 scores and levodopa response.Discussion: The primary risk factors for lower extremity venous thrombosis were found to be age, d-dimer levels, and low-dose levodopa. Therefore, for elderly patients with early-stage PD, it is crucial to conduct d-dimer and lower extremity vascular ultrasound tests. The prevention of venous thrombosis in the lower extremities of early PD patients is of utmost importance.Keywords: deep vein thrombosis, early-stage, Parkinson’s disease, ultrasonography, risk

Hanrui Fan,1 Ping Xu,1 Enming Zhang,1 Xi Meng,2 Jianmei Xia,3 Yong Fei,3 Ming Yao3 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Sci-Tech University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology and Pain, The First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Yong Fei, Department of Anesthesiology and Pain, The First Hospital of Jiaxing, 1882 Zhong-Huan-South Road, Jiaxing, 314000, People’s Republic of China, Email jxfy6666662022@163.comBackground: Current studies mostly suggest that hyperhidrosis is caused by relative sympathetic hyperactivity. Sympathetic radiofrequency thermocoagulation is widely used in clinics. Previous studies have demonstrated that surgery at T3 is effective and safe compared with higher levels, so craniofacial hyperhidrosis in our hospital is selected to be treated at T3. However, some patients pursue repeat medical treatment due to an increase in hyperhidrosis at the original site after surgery. Previous studies have demonstrated the significance of Perfusion index (PI) value in the recurrence of palmar hyperhidrosis, but there is no relevant study on craniofacial hyperhidrosis.Methods: Clinical data from patients with craniofacial hyperhidrosis, who underwent T3 sympathetic radiofrequency thermocoagulation at Jiaxing First Hospital (Jiaxing, China) between January 1, 2018 and December 31, 2021, were analyzed. Recurrence in patients 1 year after surgery was recorded through a case search and telephone follow-up system that registered patient information. Clinical data were analyzed using binary logistic regression analysis to investigate risk factors associated with recurrence in patients with craniofacial hyperhidrosis 1 year after surgery.Results: Of 83 patients included in the present study, 34 (40%) experienced increased craniofacial sweating 1 year after surgery. Results of univariate logistic regression analysis revealed that computed tomography (CT) scan count, increase in pulse index (PI) at the fingertips, and differences in forehead temperature were potential risk factors for postoperative recurrence in patients with craniofacial hyperhidrosis (p< 0.2), and the results were consistent on both sides. Three potential risk factors were included in the multivariate logistic regression analysis and results revealed that the risk for recurrence was reduced by 48% (left side) and 67% (right side) for every 1 unit increase in PI value.Conclusion: A small increase in PI was an independent risk factor for recurrence of hyperhidrosis in patients with craniofacial hyperhidrosis after undergoing T3 sympathetic radiofrequency thermocoagulation.Keywords: ephidrosis, craniofacial hyperhidrosis, sympathetic radiofrequency thermocoagulation

Janet Pope,1 Axel Finckh,2 Lucia Silva-Fernández,3 Peter Mandl,4 Haiyun Fan,5 Jose L Rivas,6 Monica Valderrama,6 Maria Montoro6 1Division of Rheumatology, University of Western Ontario, London, Ontario, Canada; 2Division of Rheumatology, University Hospital of Geneva, Geneva, Switzerland; 3Rheumatology Department, A Coruña University Hospital Complex, A Coruña, Spain; 4Division of Rheumatology, Medical University of Vienna, Vienna, Austria; 5Pfizer Inc, Collegeville, PA, USA; 6Pfizer SLU, Madrid, SpainCorrespondence: Maria Montoro, Pfizer SLU, Madrid, Spain, Email maria.montoro@pfizer.comPurpose: To evaluate the characteristics, efficacy, and retention of tofacitinib monotherapy in patients with rheumatoid arthritis using data from randomized controlled trials (RCTs) and real-world data (RWD).Patients and Methods: Three patient groups receiving tofacitinib 5 mg twice daily (BID) monotherapy were defined for post hoc RCT/long-term extension (LTE) analyses: (1) disease-modifying antirheumatic drug (DMARD)-inadequate responder patients from phase 3/3b/4 RCTs; (2) methotrexate-naïve patients from a phase 3 RCT; and (3) index study patients continuing in an LTE study. Outcomes included low disease activity (LDA)/remission rates defined by Clinical Disease Activity Index (CDAI); Disease Activity Score in 28 joints (DAS28-4), erythrocyte sedimentation rate; DAS28-4, C-reactive protein (DAS28-4[CRP]); and rates of/time to discontinuation due to lack of efficacy/adverse events. RWD were identified by non-systematic literature searches of PubMed, Embase, and American College of Rheumatology/European Alliance of Associations for Rheumatology congress abstracts (2012– 2022).Results: RCT/LTE analyses included 1000/498 patients receiving tofacitinib 5 mg BID monotherapy. Baseline disease activity was high; patients tended to receive concomitant glucocorticoids; most were biologic DMARD-naïve. CDAI LDA rates were 32.2– 62.2% for Groups 1/2 (months 3– 12) and 64.0– 70.7% for Group 3 (months 12– 72). In Groups 1, 2, and 3, 4.0%, 15.6%, and 27.7% of patients, respectively, discontinued tofacitinib monotherapy due to lack of efficacy/adverse events. From 11 RWD publications, 16.6– 66.1% received tofacitinib monotherapy. Consistent with clinical data, tofacitinib monotherapy effectiveness (month 6 CDAI LDA, 30.2%; month 3 DAS28-4[CRP] remission, 53.4%) and persistence were observed in RWD, with retention comparable to tofacitinib combination therapy.Conclusion: Tofacitinib monotherapy demonstrated clinically significant responses/persistence in RCT/LTE analyses, with effectiveness observed and persistence comparable to combination therapy in RWD.Trial Registration: NCT00814307, NCT02187055, NCT01039688, NCT00413699, NCT00661661 (ClinicalTrials.gov).Keywords: autoimmune, JAK inhibitor, clinical practice, long-term, efficacy, retention

Shenjiao Wang,1,2,&ast; Xin Zou,3– 5,&ast; Jianguang Fu,1 Fei Deng,1 Huiyan Yu,1 Huan Fan,1 Qigang Dai,1 Qingxiang Shang,5 Ke Xu,1 Changjun Bao1,5 1Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People’s Republic of China; 2Ili Kazakh Autonomous Prefecture Center for Disease Control and Prevention, Ili, Xinjiang, People’s Republic of China; 3Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Viral Infectious Diseases, Chongqing, People’s Republic of China; 5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu; Changjun Bao, Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), No. 172, Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +86-18915999237, +86-18118996911, Email xuke923@163.com; bao2000_cn@163.comBackground: Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province.Methods: Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed.Results: Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes.Conclusion: The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.Keywords: human adenovirus, whole genome sequencing, phylogenetic analysis, recombination

Xian He,1,2 Xin Ran,1 Dan Liang,2 Hongxia Fan,3 Yuping Ran1 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 3Department of Ultrasonic, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yuping Ran, Tel +8618980601697, Email ranyuping@vip.sina.comAbstract: An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.Keywords: infantile hemangioma, cutaneous, hepatic, itraconazole oral solution, dermoscopy, color ultrasonic

Xing Wang,&ast; Dong Zhang,&ast; Qingxia Lin, Changying Niu, Huiping Fan, Mogen Zhang, Xiangfeng Yuan, Weiyuan Ma Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfeng Yuan; Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China, Tel +86-536-3081272, Email nsmcyxf@126.com; fymaweiyuan@wfmc.edu.cnAbstract: Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported. The mean age at onset was 42.6 years, and the mean disease duration was 3 years. Four patients had ADF on the hands, and 1 patient had ADF on the foot. The clinical manifestations were all solitary, skin-colored papules, with a firm texture and smooth surface, protruding from the skin surface. In 3 patients, ADF manifested as columnar protrusions, and in 2 patients, ADF manifested as dome-shaped protrusions. For all 5 patients, the diameters of the lesions were < 1 cm. Clinically, all 5 patients were misdiagnosed (ie, eccrine poroma (EP), common warts, rudimentary polydactyly, pyogenic granuloma (PG), and acral fibroma). All cases of ADF were confirmed by histopathology. The histopathological manifestations of ADF were as follows: finger-like protrusions on the skin surface; collagen fiber bundles running vertically to the epidermis seen in the dermis; and thick red-stained collagen fibers connected with the normal dermal connective tissue below. All 5 patients underwent surgical resection; the distance between the incision margin and the edge of the tumor was 2– 3 mm, and the surgical depth was the deep dermis. No recurrence was observed in more than half a year of follow-up after surgery.Keywords: acquired digital fibrokeratoma, clinical manifestation, histopathology, surgical resection

Yuyi Yuan,1,&ast; Fang Wang,2,&ast; Xingxing Liu,1,&ast; Bo Shuai,1 Heng Fan1 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Rehabilitation Medicine, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Jingshan, Hubei, 431800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Shuai; Heng Fan, Email bo_shuai@hust.edu.cn; fanheng009@aliyun.comAbstract: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients’ quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.Keywords: ulcerative colitis, AMPK, colitis-associated biological processes, traditional Chinese medicine monomers

Xue Zhang,1 Haoran Zhang,1 Zonghao Zhang,1 Hua Fan,2 Shuwen Li1 1School of Nursing, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Hepatobiliary Surgery, Anhui Provincial Hospital, the First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Shuwen Li, School of Nursing, Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Email lishuwen@ahmu.edu.cnPurpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression.Patients and Methods: A total of 223 postoperative PLC patients were recruited from two public hospitals in Anhui Province, China. All participants completed the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Connor-Davidson Resilience Scale (CD-RISC). The mediating effect of resilience was estimated using the bootstrap method via IBM SPSS AMOS 26.0.Results: The mean HADS score was 12.37 ± 6.03 points in postoperative PLC patients. Among these patients, 78 (34.98%) had anxiety, and 64 (28.70%) had depression, as indicated by a subscale score ≥ 8. Pearson correlation analysis revealed that anxiety/depression was positively associated with symptom burden (p

Jiaxin Yu,1,2 Wei Zuo,1,2 Hongwei Fan,1,3 Jiayu Wu,1,2 Luyao Qiao,1,2,4 Benyu Yang,1,2,5 Wenxi Li,1,2,5 Yang Yang,1,2,&ast; Bo Zhang1,2,&ast; 1Department of Pharmacy, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Infectious Medicine, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yang; Bo Zhang, Department of pharmacy, Peking Union Medical College Hospital, Dongdan Campus, No. 1 Shuaifuyuan Wangfujing Dongcheng, District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69156527, Email yangyangsdu2010@126.com; zhangbopumch@163.comPurpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT).Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively.Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (> 3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (< 3.75 g/d, p = 0.03).Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage > 3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.Keywords: ceftazidime-avibactam, renal replacement therapy, infections, intensive care unit, carbapenem-resistant gram-negative bacteria

Tao Liu,1,&ast; Yue Li,2,&ast; Ji Li,1 Haojun Fan,1 Chunxia Cao1 1Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, People’s Republic of China; 2College of Management and Economics, Tianjin University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxia Cao, Institute of Disaster and Emergency Medicine, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, People’s Republic of China, Tel +86 02227893596, Fax +86 02227893596-307, Email caochunxia@tju.edu.cnBackground: Injury is one of the leading causes of mortality and disability worldwide. It is a major contributor to the overall burden of disease. This study aimed to analyze the temporal trend, research focus and future direction of research related to injury burden.Methods: Publications on injury burden published between January 1998 and September 2022 were extracted from the Web of Science Core Collection (WoSCC) through topic advanced search strategy. Microsoft Excel, RStudio, VOSviewer, and CiteSpace were used to extract, integrate, and visualize bibliometric information.Results: A total of 2916 articles and 783 reviews were identified. The number of publications on injury burden showed a steady upward trend. The United States of America (USA) (n=1628) and the University of Washington (n=1036) were the most productive country and institution. High-income countries started research in this domain earlier, while research in low- and middle-income countries began in recent years. Lancet was the most influential journal. Public, environmental occupational health, general medicine and neurology were the predominant research domains. Based on keyword co-occurrence analysis, the research focus was divided into five clusters: injury epidemiology and prevention, studies related to the global burden of disease (GBD), risk factors for injury, clinical management of injury, and injury outcome assessment and economic burden.Conclusion: The burden of injury has drawn increasing attention from various perspectives over the years. The research field on injury burden is also becoming more and more extensive. However, there are some gaps among different countries or regions, and more attention needs to be paid to low and middle-income countries.Keywords: injury burden, bibliometric analysis, trend, focus, VOSviewer, CiteSpace

Junli Ding,1,&ast; Hao Wang,1,&ast; Rui Hou,1,&ast; Yuxin Shi,1 Honghong Fan,1 Yuting Li,1 Jie Mei,1 Qinglin Zhang,2 Tingyan Ruan,1 Junying Xu1 1Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junying Xu; Tingyan Ruan, Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi, Jiangsu, 214023, People’s Republic of China, Tel/Fax +86-510-82700775, Email doctorxjy123@163.com; ruantingyan165@163.comBackground: Immune checkpoint inhibitors have achieved limited clinical effectiveness in colon cancer. Stem memory T cells (TSCMs) and in-situ cytotoxic T cells are dominant contributors to host immunity. Currently, data on the correlation between TSCM and T cell abundance and clinicopathological characteristics in colon cancer are largely unavailable.Methods: In-situ cytotoxic T cells are identified based on the quantification of CD3+ and CD8+ markers using immunohistochemistry (IHC) in the core of the tumor and the invasive margin of the tumor. The expression of representative markers of TSCMs, CD27 and CD95, was assayed using IHC in colon cancer tissues. Correlations between the levels of each marker and the clinicopathological characteristics as well as prognosis were evaluated.Results: High densities of CD3+ and CD8+ T cells correlated with stage I-II tumors, whereas a lower infiltration of cytotoxic T cells correlated with advanced-stage tumors. CD27 and CD95 were both expressed in the membrane of T cells present in the tumor stroma and their levels showed a negative correlation with the TNM stage. CD3, CD8, and CD27 were expressed at the same locations simultaneously, indicating their coordinated action against cancer. In addition, cytotoxic T cell densities and CD27 and CD95 expression remained independent prognostic factors for overall survival.Conclusion: In-situ cytotoxic T cells and TSCMs play important roles in colon cancer development. TSCMs marker CD27 and CD95 were both indicators of survival in patients with colon cancer. Thus, it is believed that TSCMs represent a desirable population for future use in combination immunotherapy.Keywords: T cell, CD27, CD95, prognosis, colon cancer

Honghong Fan,&ast; Yuxin Shi,&ast; Huiyu Wang, Yuting Li, Jie Mei, Junying Xu, Chaoying Liu Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoying Liu; Junying Xu, Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi, Jiangsu, 214023, People’s Republic of China, Tel/Fax +86-510-82700775, Email liuchaoying666@163.com; doctorxjy123@163.comBackground: Immunotherapy drugs, immune checkpoint inhibitors (ICIs), have been approved for first- and second-line treatment of non-small cell lung cancer (NSCLC), but only a portion of patients respond to ICIs. It is crucial to screen the beneficiaries of immunotherapy through biomarkers accurately.Methods: Several datasets were used to explore the predictive value for immunotherapy and immune relevance of guanylate binding protein 5 (GBP5) in NSCLC, including the GSE126044 dataset, The Cancer Genome Atlas (TCGA) dataset, Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, the Kaplan–Meier plotter dataset, the HLuA150CS02 cohort, and the HLugS120CS01 cohort.Results: GBP5 was upregulated in tumor tissues but associated with a good prognosis in NSCLC. Moreover, our findings demonstrated that GBP5 was strongly correlated with the expression of many immune-related genes, TIIC levels, and PD-L1 expression based on RNA-seq data onto online databases and validation of the NSCLC tissue microarray using IHC staining. Moreover, pan-cancer analysis has shown that GBP5 was a factor in identifying immuno-hot tumors, except for a few tumor types.Conclusion: In summary, our current research suggests that GBP5 expression is a potential biomarker for predicting the outcome of NSCLC patients treated with ICIs. More research with large-scale samples is needed to determine their value as biomarkers of ICIs benefit.Keywords: GBP5, biomarker, immunotherapy, NSCLC, bioinformatics

Tao Liu,1,&ast; Xin Liu,1,&ast; Yue Li,1 Aitian Wang,2 Shuohua Chen,3 Shouling Wu,3 Shike Hou,1 Haojun Fan,1 Chunxia Cao1 1Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, People’s Republic of China; 2Department of Intensive Medicine, Kailuan General Hospital, Tangshan, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxia Cao; Haojun Fan, Institute of Disaster and Emergency Medicine, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, People’s Republic of China, Tel +86 02227893596, Fax +86 02227893596-307, Email caochunxia@tju.edu.cn; fanhj@tju.edu.cnPurpose: Empirical data on the association between traumatic injury and abnormal glucose metabolism risk is limited. This study aimed to investigate the association between traumatic injury and abnormal glucose metabolism.Patients and Methods: This study included 153,162 participants in the Kailuan Study from 2006 to 2013. Participants with abnormal glucose metabolism at baseline were excluded. All participants were monitored every two years until December 31, 2019. During follow-up, 1915 subjects with a first traumatic injury (defined as a physical injury caused by an external force) were identified. For each subject with traumatic injury, one control subject was randomly selected and matched for age (± 3 years) and sex. A total of 3830 subjects were included in the final analysis. Cox proportional hazards models were used to examine the association between traumatic injury and the subsequent risk of abnormal glucose metabolism.Results: During a median follow-up of 6.91 (3.57– 9.41) years, 990 abnormal glucose metabolism events occurred. After adjustment for demographics, lifestyle behaviors, and traditional risk factors, those who had traumatic injury compared to controls were 32% more likely to develop any abnormal glucose metabolism (hazard ratio [HR] 1.32; 95% confidence interval [CI]1.16– 1.49), including impaired fasting glucose (IFG) (HR 1.29; 95% CI 1.12– 1.48) and diabetes (HR 1.37; 95% CI 1.10– 1.70). The risks for abnormal glucose metabolism, IFG, and diabetes in subjects with moderate-severe injury were higher than in subjects with mild injury for the 1-year follow-up period, while the association was not significantly different by injury severity for the whole follow-up period.Conclusion: Traumatic injury was associated with an increased risk of abnormal glucose metabolism. However, the risks of outcome events decreased as the follow-up period extended. Improved short- and long-term prevention and management strategies for controlling glucose are needed for individuals with traumatic injury.Keywords: traumatic injury, glucose metabolism, diabetes, impaired fasting glucose, cohort study

Xiaoya Liu,1,2 Haiyang Fan,3 Zhiyun Meng,2 Zhuona Wu,2 Ruolan Gu,2 Xiaoxia Zhu,2 Hui Gan,2 Guifang Dou2 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, 518026, People’s Republic of China; 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, 100850, People’s Republic of China; 3Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, 518102, People’s Republic of ChinaCorrespondence: Guifang Dou; Hui Gan, Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, 100850, People’s Republic of China, Tel +86 10 66932951, Fax +86 10 66931993, Email dougf@bmi.ac.cn; ganh2003@163.comIntroduction: Silver sulfadiazine (AgSD) is widely used in burn wound treatment due to its broad-spectrum antibacterial activity. However, its application in wound healing is greatly hindered by the low solubility of AgSD particles and their cellular cytotoxicity. Herein, we studied the safety and in vivo efficacy of nano-sized silver sulfadiazine loaded in poloxamer thermosensitive hydrogel (NS/Gel).Methods: In NS/Gel, silver sulfadiazine was prepared into silver sulfadiazine nanosuspension (NS) to improve the solubility and enhance its antibacterial activity, whereas the poloxamer thermosensitive hydrogel was selected as a drug carrier of NS to achieve slow drug release and reduced cytotoxicity. The acute toxicity of silver sulfadiazine nanosuspension was first evaluated in healthy mice, and its median lethal dose (LD50) was calculated by the modified Karber method. Furthermore, in vivo antibacterial effect and wound healing property of NS/Gel were evaluated on the infected deep second-degree burn wound mice model.Results: The mortality ratio of mice was concentration-dependent, and the LD50 for silver sulfadiazine nanosuspension was estimated to be 252.1 mg/kg (230.8 to 275.4 mg/kg, 95% confidence limit). The in vivo dosages used for burn wound treatment (40– 50 mg/kg) were far below LD50 (252.1 mg/kg). NS/Gel significantly accelerated wound healing in the deep second wound infection mice model, achieving > 85% wound contraction on day 14. Staphylococcus aureus in the wound region was eradicated after 7 days in NS/Gel group, while the bacterial colony count was still measurable in the control group. Histological analysis and cytokines measurement confirmed that the mice treated with NS/Gel exhibited well-organized epithelium and multiple keratinized cell layers compared to control groups with the modulated expression of IL-6, VEGF, and TGF-β.Conclusion: The combination of silver sulfadiazine nanosuspension and thermo-responsive hydrogel has great potential in clinical burn wound treatment.Keywords: silver sulfadiazine, antibacterial agent, thermosensitive hydrogel, acute toxicity, burn wound model, median lethal dose

Hai Fan,1 Yuesong Wang,1 Xuezhong Wang,1 Xuebin Dong,1 Xuwu Shao,1 Fei Yang2 1Department of Cardiovascular Medicine, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of China; 2Department of Laboratory, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of ChinaCorrespondence: Hai Fan, Tel +86-18255552083, Email 491640302@qq.comPurpose: This study aimed to investigate the effect of emergency percutaneous coronary intervention (PCI) combined with sacubitril-valsartan (Entresto) on the cardiac prognosis in patients with acute myocardial infarction (AMI).Patients and Methods: A total of 78 AMI patients who were treated in our hospital between January 2020 and September 2021 were included and randomly divided into treatment group and control group (n=39 per group). In the control group, patients were treated with primary PCI combined with irbesartan; in the treatment group, patients were treated with primary PCI combined with Entresto; pharmacotherapy lasted for 3 months. The left ventricular remodeling indexes, serum N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum homocysteine (HCY), cystatin C (CysC) and results of 6-minute walk test (6MWT) before and after treatment were compared between two groups. The incidence of major adverse cardiovascular events (MACE) was determined and compared between them.Results: (1) Before treatment, there were no marked differences in the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), NT-proBNP, left ventricular ejection fraction (LVEF), HCY, CysC, and results of 6MWT between two groups (P> 0.05). After treatment, the LVEDS, LVEDD, NT-proBNP, HCY and CysC in the control group were significantly higher than in the treatment group (P< 0.05). The recovery of LVEF and 6MWT in the treatment group was significantly better than in the control group (P< 0.05). After treatment, there was no significant difference in the IVST between two groups (P> 0.05). (2) The incidence of MACE in the control group was significantly higher than in the treatment group (P< 0.05).Conclusion: Compared with irbesartan, Entresto can further improve the cardiac function, prevent ventricular remodeling, and further optimize the clinical efficacy of PCI in AMI patients.Keywords: percutaneous coronary intervention, sacubitril-valsartan, acute myocardial infarction, ventricular remodeling

Yuying Lu,1– 5 Qianlin Li,1– 5 Huahao Fan,6 Conghui Liao,1– 5 Jingsong Zhang,1– 5 Huan Hu,1– 5 Huaimin Yi,1– 5 Yuanli Peng,1– 5 Jiahai Lu,1– 5 Zeliang Chen1– 3,7 1One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Guangzhou, People’s Republic of China; 3Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou, People’s Republic of China; 4Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, People’s Republic of China; 5Hainan Key Novel Thinktank “Hainan Medical University ‘One Health’ Research Center”, Haikou, People’s Republic of China; 6College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, People’s Republic of China; 7Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao, People’s Republic of ChinaCorrespondence: Jiahai Lu; Zeliang Chen, One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China, Email lujiahai@mail.sysu.edu.cn; chenzliang5@mail.sysu.edu.cnBackground: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies.Methods: Four nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods.Results: Three of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 μg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 μg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary.Conclusion: Our study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.Keywords: COVID-19, bio-nanotechnology, self-assembly, nanobody multimers, thermal stability

Haiqing Fan &ast;, Yue Yu &ast;, Jinhui Du, Likun Liu, Yilin Luo, Hui Yu, Xin Liao Department of Medical Imaging, The Affiliated Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, 550004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Liao, Department of Medical Imaging, The Affiliated Hospital of Guizhou Medical University, No. 29 Guiyi Street, Yunyan District, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Tel +86 13765065226, Email liaoxinlxlx@126.comObjective: To investigate the clinical, imaging, and pathological features of gliosarcoma.Methods: The clinical data of 14 patients with gliosarcoma confirmed by surgery and pathology at our hospital between 2010 and 2021 were analyzed retrospectively, and the relevant literature was reviewed.Results: In all 14 cases, the gliosarcoma was located in the supratentorial brain parenchyma and involved a single lesion. There were more male patients (64.3%) than female patients (35.7%), and 57.1% of all the patients were 40– 60 years of age. The prognosis of all 14 patients was poor, and the average survival time was approximately seven months. The computed tomography findings revealed mostly mixed density lesions, and some cases were complicated with bleeding. The magnetic resonance imaging revealed irregularly shaped mass lesions of different sizes, with uneven or circular enhancement. Cystic degeneration and necrosis could be seen in all the masses, some of which showed signs of bleeding and were surrounded by different degrees of edema and space-occupying effects. The pathological examination revealed that the tumors had bidirectional differentiation of the glial and sarcoma components, while the immunohistochemistry examination revealed glial fibrillary acidic protein-positive and reticular fiber-positive staining in the sarcoma.Conclusion: The clinical manifestations of gliosarcoma are nonspecific, but imaging reveals that the condition has certain characteristics, typically consisting of a huge supratentorial mass, with an irregular heterogeneous periphery or obvious mass-like augmentation after enhancement. The final diagnosis depends on the results of a pathological examination.Keywords: brain, gliosarcoma, computed tomography, magnetic resonance imaging, pathology

YingLu Wang,1,&ast; Chang Liu,1,&ast; Liping Liu,1,&ast; Xiaoli Chen,1 Lu Wei,1 Jie Liu,1 Sheng Peng,2 Jingjiang Pi,3 Qi Zhang,3 Brian Tomlinson,4 Paul Chan,5 Lin Zhang,1 Huimin Fan,1 Liang Zheng,1 Zhongmin Liu,1 Yuzhen Zhang1 1Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 5Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzhen Zhang; Zhongmin Liu, Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Tel +86 21-61569673, Email yzzhang-tj@tongji.edu.cn; liu.zhongmin@tongji.edu.cnPurpose: With increase of population aging, the prevalence of atherosclerotic cardiovascular disease (ASCVD) and elevated serum thyroid stimulating hormone (TSH) in elderly is increasing. High TSH level was reported to be associated with ASCVD and CVD mortality; however, few are studied in Chinese population, especially in the elderly. This study aimed to investigate the prevalence of elevated serum TSH and ASCVD in an elderly population of Chinese community and to explore the association between high serum TSH and ASCVD or CVD mortality.Patients and Methods: We conducted a study involving 3814 adults who were at least 60 years of age. Questionnaires, physical examinations, and laboratory blood samples were collected in 2014, and a 78-months follow-up for cardiovascular and all-cause mortality was performed till December of 2020. Logistics regression was used to analyze the association between TSH and ASCVD. We used Cox models to assess the hazard ratios (HRs) for all-cause and CVD mortality across changes in serum TSH.Results: In this study, the prevalence of the elevated serum TSH was 19.8%, and significantly higher in women than in men (24.5% vs 13.9%, p < 0.001). The prevalence of ASCVD was 21.7%. In logistics regression models, elevated TSH was associated with ASCVD after adjusting for the risk factors of ASCVD in people over the age of 70 years (adjusted OR 1.054, P = 0.014). After a follow-up of 6.5 years, total 441 (11.6%) all-cause death and 174 (4.6%) death of CVD were observed. In Cox regression model, no significant correlation was found between TSH and all-cause mortality or CVD mortality in the elderly population.Conclusion: In the elderly population, there is high prevalence of elevated serum TSH and ASCVD. Elevated TSH seemed to be not associated with risk of all-cause or CVD mortality.Keywords: cardiovascular disease, thyroid stimulating hormone, mortality, community-dwelling elderly

The differentiation of pluripotent stem cells in three-dimensional cultures can recapitulate key aspects of brain development, but protocols are prone to variable results. Here we differentiated multiple human pluripotent stem cell lines for over 100 d using our previously developed approach to generate brain-region-specific organoids called cortical spheroids and, using several assays, found that spheroid generation was highly reliable and consistent. We anticipate the use of this approach for large-scale differentiation experiments and disease modeling.

Qin Lan,1,2,&ast; Yuming Zhang,3,&ast; Fang Lin,1,2 Qingshu Meng,1,2 Nicholas Buys,4 Huimin Fan,1,2 Jing Sun3,4 1Shanghai East Hospital, Tongji University, Shanghai, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia; 4Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia&ast;These authors contributed equally to this workCorrespondence: Jing Sun, School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia, Tel +61756780924, Fax +61756780303, Email j.sun@griffith.edu.au Huimin Fan, Shanghai East Hospital, Tongji University, Shanghai, People’s Republic of China, Email frankfan@tongji.edu.cnPurpose: This study aimed to investigate the association between sex-specific baseline serum phosphate and the incidence of new-onset cardiometabolic disease in a cohort of Shanghai-based older Chinese individuals.Patients and Methods: A community cohort of 5000 disease-free Chinese men and women was recruited in 2013 and followed until 2017 for the development of cardiometabolic disease. Participants underwent index and follow-up health screens at the Tongji Medical School affiliated Shanghai East Hospital, including blood biochemistry analysis, anthropometric measurements, interview on health-related behaviors, and clinical evaluation.Results: Higher baseline serum phosphate (> 1.25 mmol/L) was significantly associated with new-onset type-2 diabetes mellitus (HR 1.730, 95% CI 1.127– 2.655) and metabolic syndrome (HR 0.640, 95% CI 1.085– 2.155) in women. Baseline serum phosphate was associated with age, BMI, waist circumference, SBP, total calcium, bicarbonate, and total cholesterol in women. The estimated risk of developing diabetes mellitus in women with inorganic phosphate > 1.25 mmol/L was 14.54%. Inorganic phosphate accounted for 9.2% of the variance explained in a total estimated 14.52% of variance attributed to BMI, total cholesterol, total calcium, waist circumference, and inorganic phosphate.Conclusion: Serum phosphate concentration showed sex-specific associations with diabetes and metabolic syndrome. Higher inorganic phosphate was associated with increased risk of developing diabetes mellitus in women. These findings may be important in the assessment of individualized metabolic risk.Keywords: inorganic phosphate, diabetes mellitus, metabolic syndrome, older women, cohort study

Heng Fan,1,&ast; Bin-jie Su,2,&ast; Jian-wei Le,1 Jian-hua Zhu1 1Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 2Department of Intensive Care Unit, Ningbo First Hospital Haishu Branch, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-hua Zhu, Department of Intensive Care Unit, Ningbo First Hospital, No.59 Liuting Road, Ningbo, Zhejiang Province, 315010, People’s Republic of China, Tel/Fax +86-574-87084625, Email zhujianhua201107@163.comPurpose: To clarify the protective effect and mechanism of salidroside (SLDS) on acute kidney injury (AKI) in septic rats.Methods: We pretreated rats with different doses of SLDS and analyzed the impact of SLDS on the survival of septic rats. We evaluated the levels of inflammatory factors in rats, the expression of NF-ƙB p65 in the kidney, and the apoptosis of kidney tubular epithelial cells (KTECs).Results: SLDS significantly decreased the mortality of septic rats, and it reduced the levels of TNF-α, IL-1β, and IL-17A in plasma and kidneys and decreased the levels of serum creatinine, plasma renal injury molecule-1 and plasma neutrophil gelatin-associated lipocalin. Moreover, SLDS could significantly decrease the expression of NF-ƙB p65 in kidney tissues and the apoptotic number of KETCs, while reducing the mRNA levels of Caspase-3 and Bax mRNA, and increasing the level of Bcl-2 mRNA.Conclusion: SLDS pretreatment protects against AKI in septic rats by inhibiting the inflammation of kidney and the apoptosis of KTECs.Keywords: salidroside, acute kidney injury, sepsis, apoptosis, inflammation

Huiyang Wang,1,&ast; Siqi Wang,2,&ast; Xisong Zhu,3 Wenxiu Ding,4 Tianlun Shen,2 Hongjie Fan,1 Yanhua Zhang,5 Lijun Peng,6 Hong Yuan,6 Xiangrui Liu,7 Jun Ling,2 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China; 3Department of Radiology, Quzhou Central Hospital Affiliated to Zhejiang Chinese Medical University, Quzhou, 324002, People’s Republic of China; 4Department of Ultrasound Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China; 5Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 6College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310030, People’s Republic of China; 7Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China, Tel +13857176538, Fax +571-86006762, Email sunjihong@zju.edu.cn Jun Ling, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China, Tel +13645717301, Fax +571-87953739, Email lingjun@zju.edu.cnPurpose: To develop an iron-based solid lipid nanoparticle (SLN) absorbable by the intestinal wall and assess the differential diagnostic value of intestinal lesions in magnetic resonance imaging (MRI).Methods: SLNs were prepared with the simultaneous loading of trivalent Fe ions (Fe3+), levodopa methyl ester (DM), and fluorescein isothiocyanate (FITC). We evaluated the particle size, loading rate, encapsulation efficiency, and cytotoxicity of SLNs. The T1 contrast effects of the FeDM-FITC-SLNs and gadolinium-based contrast agent (GBCA) were compared in different mouse models: acute ulcerative colitis (AUC), chronic ulcerative colitis (CUC), colon adenocarcinoma (COAD), and normal control. MRI was performed in the same mouse with intravenous injection of GBCA on day 1 and enema of FeDM-FITC-SLNs on day 2. The signal-to-noise ratios (SNRs) were compared using one-way analysis of variance. Tissues were then collected for histology.Results: The average particle size of FeDM-FITC-SLN was 220 nm. The mean FeDM loading rate was 94.3%, and the encapsulation efficiency was 60.3%. The relaxivity was 4.02 mM− 1·s− 1. After enema with FeDM-FITC-SLNs, MRI showed the following contrast enhancement duration: AUC = COAD > normal > CUC. Confocal fluorescence microscopy confirmed that FeDM-FITC-SLNs were mainly distributed in the intestinal mucosa and tumor capsule.Conclusion: Iron-based SLNs are promising alternatives for contrast enhancement at T1-weighted MRI and will help in the differential diagnosis of intestinal bowel diseases (IBDs).Keywords: solid lipid nanoparticles, magnetic resonance imaging, contrast agent, ferric iron, intestinal bowel diseases

Dehui Li, Huanfang Fan, Jingfei Dong, Chunxia Sun, Yifan Su, Jiao Liu, Yiting Gu Hebei Province Hospital of Chinese Medicine;The First Affiliated Hospital of Hebei University of Chinese Medicine, Shi Jiazhuang, 050011, People’s Republic of ChinaCorrespondence: Dehui Li Email 258289951@qq.comObjective: The specific mechanism of Xihuang Pill in the treatment of breast precancerous lesions and breast cancer has not yet been elucidated.Methods: In our study, BATMAN-TCM (a Bioinformatics Analysis Tool for Molecular mechanisms of Traditional Chinese Medicine) was used to forecast the relationship among chemical components, immune targets, and diseases of each herb in Xihuang Pill and constructed a component-target-disease network. Taking breast precancerous lesion model rats as the research object, the molecular mechanism of Xihuang Pill regulating immunity was analyzed.Results: BATMAN-TCM prediction showed that 309 genes were enriched in the biological process of “immune system response”, which was the target of Xihuang Pill to regulate the immune system. The target of breast cancer disease and the genes related to Xihuang Pill’s immune system response were crossed, and 88 cross genes were obtained. According to the enrichment results of GO/KEGG pathway, T cell activation was found to be the most relevant. We select Th1 cells (IL-2, IFN-γ) and Th2 cells (IL-4, IL-10) among them for animal experiment verification. The results show that Xihuang Pill can upregulate the serum IFN-γ and IL-2 levels, reduce the IL-4 and IL-10 levels, and regulate the balance of Th1/Th2 cells in the peripheral blood of rats with breast precancerous lesions.Conclusion: Xihuang Pill targets a variety of immune-related molecules related to breast precancerous lesions and is a traditional Chinese medicine formula that effectively regulates immune function.Keywords: BATMAN-TCM, Xihuang Pill, breast precancerous lesions, Th1/Th2

Dong Liu,1,2 Da Chuan Liu,3 Hao Fan,4,5 Yu Wang6 1Development Chongqing University of Education, Chongqing, People’s Republic of China; 2Education Major in Physical Education, University of Perpetual Help System DALTA Las Pinas, Manila, Philippines; 3Student Affairs Department, Jiangmen Preschool Education College, Jiangmen, Guangdong, People’s Republic of China; 4School of Tourism and Service Management, Chongqing University of Education, Chongqing, People’s Republic of China; 5Cultural Industries and Cultural Policy, Yuan Ze University, Taoyuan, Taiwan; 6Orthopedics Department, General Hospital of Northern Theatre Command, Liaoning Province, People’s Republic of ChinaCorrespondence: Yu WangOrthopedics Department, General Hospital of Northern Theatre Command, No. 83 Wenhua Road, Shenhe District, Shenyang, Liaoning Province, 110016, People’s Republic of ChinaTel +86-18609886338Email wangyu16732@163.comAim: The purpose of this study is to study the antioxidant effect of Lactobacillus fermentum CQPC08 (CQPC08) on exercise-induced fatigue, and the beneficial intervention of GOS on CQPC08.Methods: We use the treadmill to establish a fatigue model caused by exercise, and perform drug treatment after exercise. We tested the exhaustive exercise time of mice; investigated the changes of mice body weight, liver index, histopathology, serum biochemical indicators and mRNA expression levels of oxidative and inflammation-related genes; and assessed the potential fatigue inhibitory effect of CQPC08, and the anti-oxidation effect of the combination of GOS and CQPC08.Results: The results suggest that CQPC08 and combination with GOS reduces fatigue-induced oxidative damage of the liver, and it decreases blood urea nitrogen (BUN), lactic acid (LA), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), malonaldehyde (MDA), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in serum. Higher levels of serum catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were found. Treatment with the CQPC08 and combination with GOS correlates with lower relative mRNA expression levels of neuronal NOS (nNOS), iNOS, and TNF-α, and with higher mRNA expression levels of catalase and copper/zinc (Cu/Zn) and manganese (Mn) SOD enzymes in the liver and muscles.Conclusion: These results suggest that CQPC08 can resolve exercise-induced fatigue by improving antioxidant ability in mice, and the combination of GOS and CQPC08 enhances this ability of CQPC08.Keywords: Lactobacillus fermentum, exercise-induced fatigue, antioxidant, GOS

Changhui Han,1 Yingjuan Liu,2 Huanfang Fan,1 Dehui Li,1 Na Guo1 1Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of China; 2Institute of Cardiovascular Sciences, University of Manchester, Manchester, UKCorrespondence: Yingjuan LiuUniversity of Manchester, 46 Grafton Street, Manchester, M13 9PT, UKEmail liuyingjuan2008@gmail.comAbstract: Cancer pain is a common problem in clinical cancer therapy. Opioid analgesia is one of the most effective drugs for pain relief with satisfying performance besides the side effect of opioid-induced constipation (OIC). Acupuncture, as a Chinese traditional non-invasive intervention, has been applied to clinical cancer pain management and functional constipation therapy. However, only a few studies have adopted this treatment for OIC patients. Due to limited numbers of investigated subjects and variability of application methods, including treatment apparatus, acupoints, durations, and sessions, the interpretation of acupuncture’s therapy effects from single-site randomized clinical trials (RCT) is limited. Therefore, we conducted a meta-analysis by collecting published data from Pubmed, Embase, Cochrane library, and Web of Science. Five RCTs focusing on the application of acupuncture with or without medication in OIC patients were included. An overall remission rate of 86.8% in the acupuncture-treated group was achieved, higher than the control group (78.9%; RR, 1.10, 95% CI [1.03, 1.18]). The symptom scores, reporting on defecation frequency, defecation straining, abdominal pain, defection time, and stool property, in acupuncture groups were lower than control groups with a standardized mean difference (SMD) of − 2.21 [− 4.15, − 0.27]. The quality of life (QOL) for patients in the acupuncture treated group increased compared to the control group with reduced PAC-QOL scores (SMD, − 1.02 [− 1.78, − 0.26]). Referring to the effects from pure acupuncture treatment (SMD, − 0.43 [− 0.83, − 0.03]), the co-intervention of acupuncture and drugs (SMD, − 1.77 [− 2.51, − 1.02]) improved the life quality of patients more remarkably (P < 0.05). Overall, our data confirmed the therapeutic effects of acupuncture in the treatment of OIC. The co-intervention of acupuncture with drugs improves the outcomes of OIC patients better than a single strategy. Combined therapy with both medicine and acupuncture has insightful potential for future clinical cancer patient management on constipation problems.Keywords: acupuncture, opioid-induced constipation, cancer, pain, meta-analysis

Dongzhu Lu,&ast; Lichang Chen,&ast; Chaofan Fan, Wenyi Zeng, Huizhen Fan, Xiping Wu, Huapeng Yu Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huapeng YuDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510220, People’s Republic of ChinaTel +86 20 61643175Fax +86 20 84306143Email huapengyu@aliyun.comPurpose: To evaluate the value of impulse oscillometry (IOS) and quantitative HRCT parameters for differentiating asthma–COPD overlap (ACO) in COPD patients.Patients and Methods: We enrolled 44 controls and 66 COPD patients, divided into the pure COPD group (n=40) and the ACO group (n=26). Spearman correlation analysis was utilized to assess the relationship between the quantitative HRCT and IOS parameters. A binary logistic regression analysis was performed to analyze the associations between the different variables and the risk of ACO. Receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff and assess the diagnostic value of relative volume change − 856 HU to − 950 HU (RVC− 856 to − 950), decrease in the resistance from 5 Hz to 20 Hz (R5-R20) and their combination in predicting ACO. Bootstrapping validation was used to evaluate the internal validation. The concordance index (C-index) and calibration plot were calculated to assess the discrimination and calibration of the prediction model.Results: Binary logistic regression analysis indicated that RVC− 856 to − 950 and the IOS parameters (R5-R20, R5, X5) were independently correlated with a higher risk of developing ACO after adjusting for age, sex, body mass index (BMI), history of smoking, exacerbation and atopy or allergic rhinitis. A correlation analysis showed a good correlation between the pulmonary function parameters and RVC− 856 to − 950, with a weaker correlation with the % area of low attenuation (LAA%) in ACO patients. Combining RVC− 856 to − 950 and R5-R20 to predict ACO, the AUC was 0.909, and the optimal cutoff value was >-0.62 for RVC− 856 to − 950 and > 0.09 for R5-R20. Good calibration and favorable discrimination were displayed with a higher C-index.Conclusion: More serious small airway impairment exists in ACO patients. The combination of RVC− 856 to − 950 and R5-R20 could be applied to differentiate ACO from COPD patients.Keywords: relative volume change − 856 HU to − 950 HU, decrease in resistance from 5 Hz to 20 Hz, quantitative HRCT, ROC curve, diagnosis

Na Zhang,1,&ast; Hui Wu,2,&ast; Yingzhi Liang,1,&ast; Jianming Ye,1 Huan Zhang,3 Yuqing Miao,3 Yane Luo,1 Haiming Fan,3 Tianli Yue1,4 1College of Food Science and Technology, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 2State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 4Laboratory of Quality and Safety Risk Assessment for Agro-Products (Yangling), Ministry of Agriculture, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yane Luo Email luoyane@nwu.edu.cnPurpose: Superparamagnetic iron oxide nanoparticles (SPIONs) have exhibited preeminent diagnosis and treatment performances, but their low internalization severely limits predesigned functions. The low cell internalization is now an urgent bottleneck problem for almost all nanomaterials. To achieve more internalization of SPIONS, recombinant M13 phage was designed for targeted delivery and smart release.Methods: M13 phages were designed to co-express exogenous SPARC binding peptide (SBP) and cathepsin B cleavage peptide (DFK), formed recombinant DFK-SBP-M13. 3.37± 0.06 nm of SPIONs were modified by 3, 4-dihydroxyhydrocinnamic acid (DHCA) to gain 10.80 ± 0.21 nm of DHCA-coated SPIONs, i.e., DHCA@SPIONs. Upon adjusting the proportions of DHCA@SPIONs and DFK-SBP-M13, the multi-carboxyl SPIONs assembled onto recombinant M13 phages via covalent bonding. The assemblies were co-cultured with MDA-MB-231 cells to interpret their internalization and smart release.Results: The “corn-like” SPIONs@DFK-SBP-M13 (261.47± 3.30 nm) assemblies have not been reported previously. The assembly was stable, dispersible, superparamagnetic and biocompatible. After co-cultivation with MDA-MB-231 cells, the SPIONs@DFK-SBP-M13 assemblies quickly bond to the cell surface and are internalized. The enrichment rate of SPIONs@DFK-SBP-M13 assembly was 13.9 times higher than free SPIONs at 0.5 h, and intracellular Fe content was 3.6 times higher at 1 h. Furthermore, the DFK peptides favored cathepsin B to cleave SPIONs from the M13 templates resulting in release of SPIONs inside cells.Conclusion: The novel SPIONs@DFK-SBP-M13 assembly can rapidly deliver SPIONs to the targeted sites and enabled smart release. The combination of genetic recombination and nanotechnology is beneficial for designing and optimizing some new nanomaterials with special functions to achieve wider applications.Keywords: M13 phage, superparamagnetic iron oxide nanoparticles, self-assembly, smart release, targeting

Hongquan Zheng,1,2 Yan Xia,3 Shengjun Qu,4 Lin Fan,2 Jingjing Zhang,1 Zhixiang Ma,1 Yangsheng Chen,4 Hongwei Fan1,2 1Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Leeway Biological Technology Co., Ltd, Nanjing, Jiangsu, People’s Republic of China; 4CP Pharmaceutical Qingdao Co., Ltd, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Hongwei FanNanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, People’s Republic of ChinaTel +86 25 5288 7030Fax +86 25 5288 7031Email fanhongwei178@sina.comYangsheng Chen 3601 Tuanjie Road, Economic and Technological Development Zone, Qingdao, People’s Republic of ChinaTel +86 18766396996Email chenys@cppqd.comPurpose: The present report describes findings from a Phase I clinical study that evaluated the single- and multiple-dose pharmacokinetics of frovatriptan succinate tablet in Chinese healthy subjects.Methods: A total of 24 healthy subjects were enrolled. In single-dose study, 2.5, 5, and 10 mg oral doses of frovatriptan succinate tablet were administrated. A 2.5 mg frovatriptan succinate tablet was administrated 12 times in 7 days in the multiple-dose study. Blood samples were collected at scheduled time points.Results: The results in single-dose study indicated that the blood levels were proportional to the administered dose, with the mean Cmax and AUClast ranging from approximately 6.27 ng/mL– 17.35 ng/mL and 92.52 h⋅ng/mL – 287.40 h⋅ng/mL over the dose range. In the multiple-dose study, moderate drug accumulation was noted, which was attributable to forvatriptan’s long t1/2 of about 26.47 to 30.63 h. Gender differences were noticed in both single- and multiple-dose study; exposure PK parameters were consistently higher in female than in male.Conclusion: These pharmacokinetic evaluations in healthy Chinese subjects found that frovatriptan succinate tablet has an acceptable pharmacokinetic profile in Chinese subjects.Keywords: frovatriptan succinate, pharmacokinetics, single-dose, multiple-dose

Hui Huang,1 Minmin Li,2 Hourui Fan,3 Ruhai Bai4 1Department of Dermatology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Nutrition and Food Hygiene, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 3Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4School of Public Affairs, Nanjing University of Science and Technology, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Ruhai BaiSchool of Public Affairs, Nanjing University of Science and Technology, No. 200, Xiaolingwei Street, Nanjing, Jiangsu, People’s Republic of ChinaEmail ruhaibai@hotmail.comPurpose: Urolithiasis is one of the commonest disease of the urinary system. This study aimed to assess the long-term urolithiasis incidence trends in China between 1990 and 2019.Patients and Methods: The incidence data of urolithiasis were extracted from Global Burden of Disease Study 2019, and an age–period–cohort framework was used to estimate the age, period, and cohort effects.Results: We found that the net drift was − 2.72% (95% CI: − 2.84% to − 2.60%) per year for men and − 2.14% (95% CI: − 2.24% to − 2.05%) per year for women, and except men in age group 0– 4, the local drift values were below 0 in all age groups (P< 0.05 for all) in both sexes during the period of 1990 to 2019. In the same birth cohort, the risk of incidence from urolithiasis rose first and then decreased with age for both sexes after controlling for period deviations, and in addition, after 20 years old, the risk of incidence of urolithiasis in men was higher than that in women (significantly with P< 0.05). In general, the estimated period and cohort relative risks were found in similar downward patterns for both sexes.Conclusion: In the past 30 years, the age-standard incidence of urolithiasis in both sex of Chinese people has decreased, but the crude incidence of urolithiasis in Chinese women has increased. Considering the aging of population structure in China, the overall number of female urolithiasis patients may increase, contributes to higher crude incidence rate. The problem of urolithiasis in Chinese women needs to be paid more attention.Keywords: age–period–cohort analysis, urolithiasis, urinary stones, urolithiasis in China

Weijian E,1 Zhixin Wang,2 Mingquan Pang,2,3 Yongliang Lu,1 Haining Fan2,3 1Centre of Medical Laboratory Technology & Laboratory Diagnostics, Affiliated Hospital of Qinghai University, Xining, Qinghai, 810001, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, Qinghai, 810001, People’s Republic of China; 3Qinghai Provincial Research Key Laboratory for Hydatid, Xining, Qinghai, 810001, People’s Republic of ChinaCorrespondence: Weijian ECentre of Medical Laboratory Technology & Laboratory Diagnostics, Affiliated Hospital of Qinghai University, 29 Tongren Road, Xining, Qinghai, 810001, People’s Republic of ChinaTel/Fax +86 971-6230672Email e_weijian220@163.comHaining FanQinghai Provincial Research Key Laboratory for Hydatid, 29 Tongren Road, Xining, Qinghai, 810001, People’s Republic of ChinaTel/Fax +86 971-6162000Email fanhaining_ve@21cn.comObjective: To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with hepatic hydatid diseases.Methods: The clinical data of 420 patients with hydatid disease who were treated in our hospital from October 2015 to October 2018 were collected from the database of our hospital. According to the postoperative pathological diagnosis, 200 patients were assigned into the alveolar echinococcosis (AE) group, and 220 patients were assigned into the cystic echinococcosis (CE) group. A total of 160 healthy examinees were enrolled as the control group. The main observation indexes included preoperative PLR and NLR. Pearson’s correlation was used to analyze the correlation between PLR and NLR with clinical indicators in HE patients, and the receiver operator characteristic (ROC) curve was used to evaluate the clinical values of PLR and NLR in diagnosing different types of hydatid diseases.Results: The results revealed that the expressions of PLR and NLR were significantly higher in the AE group than in the CE and control groups (P< 0.05). The results of multiple linear regression analysis revealed that PLR was positively correlated with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase (P< 0.05). NLR was correlated with albumin content (P< 0.05). ROC curve analysis results revealed that the area under the curve (AUC) of PLR and NLR for AE was 0.800 and 0.700 respectively, and the AUC for CE was 0.78 and 0.75 respectively.Conclusion: The NLR and PLR of AE patients were higher than those of CE patients, and the high inflammation of CE patients may be correlated to the reproductive mode of Echinococcus multilocularis. PLR and NLR have certain diagnostic values for disease classification, but PLR has higher specificity when compared with NLR.Keywords: platelet-to-lymphocyte ratio, PLR, neutrophil-to-lymphocyte ratio, NLR, alveolar echinococcosis, cystic echinococcosis, inflammation

Fa Jin, Weiyang Ou, Boyang Wei, Haiyan Fan, Chengcong Wei, Dazhao Fang, Guangxu Li, Wenchao Liu, Jiahui Liu, Lei Jin, Xuying He, Chuanzhi Duan Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of ChinaCorrespondence: Chuanzhi Duan; Xuying He Tel +86 135 399 622 33; +86 136 888 771 33Fax +86 206 164 3010Email doctor_duanzj@163.com; 2517079319@qq.comBackground: Ischemic stroke is one of the leading causes of mortality and disability worldwide. Following stroke, there is secondary neuroinflammation that promotes further injury. Identifying the long non-coding RNA (lncRNA) involved in neuroinflammation after cerebral ischemic stroke will promote the discovery of potential therapeutic targets.Methods: We identified differentially expressed genes from genome-wide RNA-seq profiles of mice with focal ischemia using Gene Ontology Term Enrichment, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment analyses. Immune cell infiltration deconvolution, protein-protein interaction network construction, and co-expression network analyses were also used to screen lncRNAs. In further experiments, lncRNA Neat1 knockdown animal models were developed by intraventricular injection of the antisense oligonucleotide before performing middle cerebral artery occlusion (MCAO). An enzyme-linked immunosorbent assay was performed to measure the level of cytokines. Hematoxylin-eosin staining and immunohistochemical staining were used to observe the changes in morphology.Results: Enrichment analysis revealed that differential mRNAs induced neuroinflammation after MCAO. Immune deconvolution showed that the proportion of microglia gradually increased while monocytes decreased within 24 h. We identified six hub lncRNAs (Neat1, Gm10827, Trp53cor1, Mir670hg, C730002L08Rik, and Mir181a-hg) that were highly correlated with activated-microglia mRNAs (cor > 0.8). We found that Neat1 had the highest correlation coefficient with pro-inflammatory factor mRNA levels. In vivo experiments demonstrated that Neat1 had abnormally high expression after MCAO. Knockdown of Neat1 could significantly alleviate brain damage by reducing the number of activated microglia and reducing their release of proinflammatory cytokines.Conclusion: We identified inflammation-associated lncRNA Neat1 as crucial, which means it is a potential target for ischemic stroke treatment.Keywords: bioinformatics, lncRNA Neat1, ischemic stroke, MCAO, microglia, neuroinflammation

Fan H, Hou J, Liu S, Xiao Z, Cui J. Cancer Manag Res. 2020;12:8363–8377. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the integrity of the flow cytometry data shown in the article. In addition, there were also concerns regarding the duplication of images in Figure 5D with those from Figure 6D in Luo et al (2020) (https://doi.org/10.2147/OTT.S278582). Specifically, Figure 5D, PC-3, #1, appears to have been duplicated with a similar image in Figure 6D, SW480, left hand panel, from Luo et al (2020). The authors did not respond to our queries and the decision was made to retract the article and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.