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Hui Liu,1,2 Xuan Xu,3 Ji Li,3 Zheyu Liu,1 Yuwen Xiong,1 Mengli Yue,4 Pi Liu1 1Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Gastroenterology Institute of Jiangxi Province, Nanchang, People’s Republic of China; 3Department of Gastroenterology, The People’s Hospital of Longhua, Shenzhen, People’s Republic of China; 4Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China, Tel +86-13507913736, Email liupi126@sina.comPurpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP. Keywords: severe acute pancreatitis, plakophilin2, capillary leak syndrome, tight junction, p38/MAPK signaling pathway

Xuefeng Bian,1,* Ting Guo,2,* Guojie Chen,2,* Dengyun Nie,2 Miao Yue,2 Yinxing Zhu,2 Mei Lin3 1Imaging Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People’s Republic of China; 2Institute of Clinical Medicine, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People’s Republic of China; 3Clinical Medical Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Lin; Yinxing Zhu, Email trylm@ntu.edu.cn; lzp_zyx@163.comPurpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI).Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial–mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed.Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras.Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.Keywords: iron–platinum magnetic nanoparticles, ovarian cancer, DDP, molecular magnetic resonance imaging, folate

Cheng Ma,1 Minnan Yue,2 Xiaoling Zhu1 1Department of Physical Education, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2School of Energy and Power Engineering, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Cheng Ma, Department of Physical education, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of China, Tel +86-13795365789, Email macheng@usst.edu.cnPurpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure.Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy.Results: A total of 969 students were recruited, with mean age of 18.73± 0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57± 0.95, 32.63± 4.07, and 27.06± 7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52– 2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12– 1.22, P < 0.001). A bachelor’s degree and being in the sophomore year were positively associated with knowledge (OR = 1.51– 4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43– 0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33– 2.57, P < 0.001). Father’s education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37– 0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72– 5.55, P < 0.001) were associated with practice.Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.Keywords: knowledge, attitude, practice, cross-sectional study, physical literacy

Zheyu Liu,1 Huajing Ke,1 Yuwen Xiong,1 Hui Liu,1 Mengli Yue,2 Pi Liu3 1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Gastroenterology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China, Tel +86- 13507913736, Email liupi126@sina.comPurpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach.Methods: Clinical data from 1274 patients with NP from 2014– 2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas.Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p< 0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas.Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.Keywords: necrotizing pancreatitis, a step-up approach, gastrointestinal fistula, minimally invasive step-up intervention

Chenxing Wei,1,&ast; Jian Chen,1,&ast; Tanveer Muhammad Anwar,2,&ast; Lingling Huang,1 Wenjie Yang,3 Xueyan Dong,1 Qiong Chen,1 Min Yue,2,4,5 Daojun Yu1,3 1Department of Medical Laboratory, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Department of Veterinary Medicine, Institute of Preventive Veterinary Sciences, Zhejiang University College of Animal Sciences, Hangzhou, 310058, People’s Republic of China; 3Department of Medical Laboratory, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Hainan Institute, Zhejiang University, Sanya, 572025, People’s Republic of China; 5State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Yue; Daojun Yu, Email myue@zju.edu.cn; yudaojun98@zju.edu.cnPurpose: Acinetobacter baumannii (A. baumannii or AB) is one of the most opportunistic, nosocomial pathogens threatening public healthcare across countries. A. baumannii has become a primary growing concern due to its exceptional ability to acquire antimicrobial resistance (AMR) to multiple antimicrobial agents which is increasingly reported and more prevalent every year. Therefore, there is an urgent need to evaluate the AMR knowledge of A. baumannii for effective clinical treatment of nosocomial infections. This study aimed to investigate the clinical distribution AMR phenotypes and genotypes, and genomic characteristics of A. baumannii isolates recovered from hospitalized patients of different clinical departments of a sentinel hospital to improve clinical practices.Methods: A total of 123 clinical isolates were recovered from hospitalized patients of different clinical departments during 2019– 2021 to analyze AMR patterns, and further subjected to whole-genome sequencing (WGS) investigations. Multi-locus sequence typing (MLST), as well as the presence of antimicrobial-resistant genes (ARGs), virulence factor genes (VFGs) and insertion sequences (ISs) were also investigated from WGS data.Results: The results highlighted that A. baumannii clinical isolates had shown a high AMR rate, particularly from the intensive care unit (ICU), towards routinely used antimicrobials, ie, β-lactams and fluoroquinolones. ST2 was the most prevalent ST in the clinical isolates, it was strongly associated to the resistance of cephalosporins and carbapenems, with blaOXA-23 and blaOXA-66 being the most frequent determinants; moreover, high carrier rate of VFGs was also observed such as all strains containing the ompA, adeF, pgaC, lpsB, and bfmR genes.Conclusion: Acinetobacter baumannii clinical isolates are mostly ST2 with high rates of drug resistance and carrier of virulence factors. Therefore, it requires measurements to control its transmission and infection.Keywords: Acinetobacter baumannii, antimicrobial resistance, genetic determinants, virulence factors, whole-genome sequencing

Yanzheng Zou,1,* Ming Yue,2,* Linna Jia,1 Yidi Wang,1 Hongbo Chen,3 Yifan Wang,3 Meiling Zhang,3 Yue Feng,4 Rongbin Yu,1 Sheng Yang,5 Peng Huang1 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Infectious Disease, Jurong Hospital Affiliated to Jiangsu University, Jurong, People’s Republic of China; 4Faculty of Life Science and Technology, Kunming University of Science and Technology, Yunnan, People’s Republic of China; 5Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Huang, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email huangpeng@njmu.edu.cn Sheng Yang, Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email yangsheng@njmu.edu.cnPurpose: It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes.Patients and Methods: A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years.Results: Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 > 3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 > 3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25.Conclusion: FIB-4 > 3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 > 3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.Keywords: chronic hepatitis C, sustained virologic response, direct-acting antivirals, serum biomarker, hepatocellular carcinoma

Zhiguo Zhang,1,2,&ast; Fangda Fu,1,2,&ast; Yishan Bian,1,2,&ast; Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

Meina Yue,1 Di Liu,1 Xiaoyu Li,1 Shurui Jin,2 Xue Hu,1 Xinfeng Zhao,1 Yidong Wu1 1Department of Clinical Laboratory, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China; 2Department of Statistics & Data Science, Carnegie Mellon University, Pittsburgh, PA, USACorrespondence: Yidong Wu, Department of Clinical Laboratory, Hangzhou Children’s Hospital, 195 Wenhui Road, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 57185463946, Email wyd721@sina.comPurpose: This research investigated the dynamics of antibiotic resistance in Salmonella and the epidemiology of Salmonella infection in children. These data can aid in the prevention and control of the Salmonella epidemic and the diagnosis and treatment of salmonellosis.Methods: In this study, we retrospectively reviewed and analysed data regarding epidemiology, clinical symptoms, Salmonella serotypes, and antibiotic resistance from the medical records of patients with Salmonella infections in Hangzhou Children’s Hospital from April 2006 to December 2021.Results: A total of 2099 Salmonella isolates were identified during the 16-year study period, and 98.6% (2069) of the isolates were isolated from stool. About 84.5% (1773/2099) of the total Salmonella isolates were detected from May to October. The median age of the 2099 children with Salmonella infection was 1.4 years (17 months) (IQR: 0.9– 2.8 years). In 1572 (74.9%) patients, the course of the disease was limited to uncomplicated gastroenteritis. S. Typhimurium (805/2099, 38.4%) was predominant, followed by S. Enteritidis (290/2099, 13.8%). The total number of serotypes and the number of less common serotypes are increasing. Nontyphoid Salmonella that cause invasive infections, including S. Typhimurium, S. Stanley, and S. Choleraesuis, accounted for 60.0% (18/30). The Salmonella strains were resistant to ampicillin, ampicillin-sulbactam, trimethoprim-sulfamethoxazole, ceftriaxone, and ciprofloxacin at percentages of 71.5%, 51.5%, 36.5%, 22.4%, and 14.7%, respectively. No imipenem-resistant strains were identified. 24.8% of the isolates exhibited multidrug resistance (MDR).Conclusion: S. typhimurium and S. enteritidis were the dominant serotypes in children (< 2 years) with salmonella-infected arrhoea in Hangzhou, China. Ongoing serotype monitoring should be necessitated and dynamic changes in serotypes should be carefully examined to prevent the sudden outbreak of foodborne illness. Salmonella exhibits a higher rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored. Therefore, clinicians should administer antibiotics judiciously according to the results of drug sensitivity tests.Keywords: Salmonella, serotype, antibiotic resistance, children; epidemiology

Huihao Zhang,1,&ast; Sai Yao,1,&ast; Zhiguo Zhang,1,&ast; Chengcong Zhou,1 Fangda Fu,1 Yishan Bian,1 Huan Luo,2 Yan Li,1 Shuxin Yan,1 Yuying Ge,1 Yuying Chen,3 Kunyu Zhan,4 Yanzhi Ge,1 Zuxiang Chen,1 Ming Yue,5 Xiaofeng Li,6 Weibin Du,1,7 Hongting Jin,1 Peijian Tong,1 Hongfeng Ruan,1,8 Chengliang Wu1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopedics and Traumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 8Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Peijian TongInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail rhf@zcmu.edu.cn; peijiantongzjtcm@163.comPurpose: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation.Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology.Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD.Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.Keywords: intervertebral disc degeneration, Liuwei Dihuang decoction, network pharmacology, pharmacological mechanisms, apoptosis

Xiaofan Luo, Meng Yue, Chenguang Li, Di Sun, Lei Wang Department of Colorectal and Anal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Lei WangDepartment of Colorectal and Anal Surgery, First Hospital of Jilin University, 71 Xinmin Road, Changchun, Jilin 130021, People’s Republic of ChinaEmail leiwang_1967@126.comBackground: Long intergenic non-protein coding RNA 239 (LINC00239) is an oncogenic long non-coding RNA in acute myeloid leukemia. We aimed to determine LINC00239 expression in colorectal cancer (CRC) and examine the influences of LINC00239 on tumor behaviors of CRC cells. Furthermore, the mechanism underlying the actions of LINC00239 in CRC was unveiled in detail.Materials and Methods: Quantitative real-time polymerase chain reaction was used to detect LINC00239 expression in CRC tissues and cell lines. CRC cell proliferation, apoptosis, migration, and invasion were investigated by cell counting kit-8 assays, flow cytometry, and cell migration and invasion assays, respectively. Tumor xenograft experiments were performed to evaluate the tumor growth of CRC cells in vivo. The interactions among LINC00239, microRNA-484 (miR-484), and kruppel-like factor 12 (KLF12) were analyzed by bioinformatics prediction, RNA immunoprecipitation and luciferase reporter assay.Results: LINC00239 was upregulated in CRC tissues and cell lines. LINC00239 knockdown impaired CRC cell proliferation, migration, and invasion and promoted apoptosis in vitro. Additionally, LINC00239 deficiency inhibited CRC growth in vivo. Mechanistically, LINC00239 functioned as a competing endogenous RNA by directly sponging miR-484, thereby enhancing KLF12 expression. Rescue experiments further corroborated that miR-484 inhibition or KLF12 overexpression reversed the inhibitory actions of LINC00239 knockdown in CRC cells.Conclusion: The LINC00239/miR-484/KLF12 pathway executed critical roles in CRC oncogenicity and may provide potential targets for CRC treatments.Keywords: long intergenic non-protein coding RNA 239, kruppel-like factor 12, CRC, miRNA sponge

Luo X, Yue M, Li C, Sun D, Wang L. Onco Targets Ther. 2020;13:12067-12081. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Following publication of the Expression of Concern for this article, concerns were raised regarding the alleged duplication of images in Figure 6D with those from Figure 5D from Fan et al (2020) (https://doi.org/10.2147/CMAR.S271021). Specifically, ● Figure 6D, SW480, left hand panel, appears to have been duplicated with a similar image in Figure 5D, PC-3, #1, from Fan et al, 2020. The authors were unable to provide an explanation for the duplicated images and the decision was made to retract the article. 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”.

In the southwestern United States, non-native grass invasions have increased wildfire occurrence in deserts and the likelihood of fire spread to and from other biomes with disparate fire regimes. The elevational transition between desertscrub and montane grasslands, woodlands, and forests generally occurs at ∼1,200 masl and has experienced fast suburbanization and an expanding wildland-urban interface (WUI). In summer 2020, the Bighorn Fire in the Santa Catalina Mountains burned 486 km2 and prompted alerts and evacuations along a 40-km stretch of WUI below 1,200 masl on the outskirts of Tucson, Arizona, a metropolitan area of >1M people. To better understand the changing nature of the WUI here and elsewhere in the region, we took a multidimensional and timely approach to assess fire dynamics along the Desertscrub-Semi-desert Grassland ecotone in the Catalina foothills, which is in various stages of non-native grass invasion. The Bighorn Fire was principally a forest fire driven by a long-history of fire suppression, accumulation of fine fuels following a wet winter and spring, and two decades of hotter droughts, culminating in the hottest and second driest summer in the 125-yr Tucson weather record. Saguaro (Carnegia gigantea), a giant columnar cactus, experienced high mortality. Resprouting by several desert shrub species may confer some post-fire resiliency in desertscrub. Buffelgrass and other non-native species played a minor role in carrying the fire due to the patchiness of infestation at the upper edge of the Desertscrub biome. Coupled state-and-transition fire-spread simulation models suggest a marked increase in both burned area and fire frequency if buffelgrass patches continue to expand and coalesce at the Desertscrub/Semi-desert Grassland interface. A survey of area residents six months after the fire showed awareness of buffelgrass was significantly higher among residents that were evacuated or lost recreation access, with higher awareness of fire risk, saguaro loss and declining property values, in that order. Sustained and timely efforts to document and assess fast-evolving fire connectivity due to grass invasions, and social awareness and perceptions, are needed to understand and motivate mitigation of an increasingly fire-prone future in the region.

Extragalactic fast X-ray transients (FXTs) are a class of soft (0.3–10 keV) X-ray transients lasting a few hundred seconds to several hours. Several progenitor mechanisms have been suggested to produce FXTs, including supernova shock breakouts, binary neutron star mergers, or tidal disruptions involving an intermediate-mass black hole and a white dwarf. We present detailed host studies, including spectroscopic observations of the host galaxies of seven XMM-Newton -discovered FXTs. The candidate hosts lie at redshifts 0.0928 < z < 0.645 implying peak X-ray luminosities of 1043 erg s−1< LX < 1045 erg s−1 and physical offsets of 1 kpc < r proj < 22 kpc. These observations increase the number of FXTs with a spectroscopic redshift measurement by a factor of 2, although we note that one event is re-identified as a Galactic flare star. We infer host star formation rates and stellar masses by fitting the combined spectroscopic and archival photometric data. We also report on a contemporaneous optical counterpart search to the FXTs in Pan-STARRS and ATLAS by performing forced photometry at the position of the FXTs. We do not find any counterpart in our search. Given our constraints, including peak X-ray luminosities, optical limits, and host properties, we find that XRT 110 621 is consistent with an supernova shock breakout (SN SBO) event. Spectroscopic redshifts of likely host galaxies for four events imply peak X-ray luminosities that are too high to be consistent with SN SBOs, but we are unable to discard either the binary neutron star or white dwarf–intermediate-mass black hole tidal disruption event scenarios for these FXTs. [ABSTRACT FROM AUTHOR]

Zhennan Yun,1 Fanqi Meng,1 Peiqiang Jiang,2 Meng Yue,1 Shiquan Li11Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaBackground and purpose: An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified.Methods: Expression levels of miR-548b in HCC tissues and cell lines were measured by reverse-transcription quantitative PCR. In vitro and in vivo functional assays were performed to determine the effects of miR-548b on the malignant phenotypes of HCC cells. In addition, the molecular mechanisms by which miR-548b regulates the initiation and progression of HCC were investigated in detail.Results: miR-548b expression was weak in HCC tissues and cell lines. The low miR-548b expression significantly correlated with tumor size, TNM stage, and venous infiltration of HCC. In addition, exogenous miR-548b expression suppressed HCC cell proliferation, colony formation, and metastasis and induced apoptosis in vitro. Silencing of miR-548b exerted an opposite effect on these characteristics of HCC cells. Furthermore, miR-548b overexpression hindered tumor growth in vivo. Mechanistic analysis identified high-mobility group box 1 (HMGB1) as a direct target gene of miR-548b in HCC cells. Moreover, an HMGB1 knockdown reproduced the effects of miR-548b upregulation on HCC cells. Recovered HMGB1 expression reversed the effects of miR-548b on HCC cells. Notably, miR-548b overexpression deactivated the PI3K–AKT pathway in HCC cells in vitro and in vivo.Conclusion: Our findings provide the first evidence that miR-548b restrains HCC progression, at least partially, by downregulating HMGB1 and deactivating the PI3K–AKT pathway. Thus, miR-548b might be a novel target for the development of new therapies for HCC.Keywords: microRNA-548b, hepatocellular carcinoma, PI3K–AKT pathway, high-mobility group box 1, HMGB1

Yun Z, Meng F, Jiang P, Yue M, Li S. Cancer Manag Res. 2019;11:5821–5834. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over alleged image duplication in Figures 6D and 8A with similar images from unrelated articles, specifically: Figure 6D, panel Hep3B 1 appears to have been duplicated with a similar image in Figure 5D from Chen et al, 2019 (https://doi.org/10.2147/OTT.S192137). Figure 6D, panel SK-HEP-1 6 appears to have been duplicated with a similar image in Figure 6D from Liu et al, 2019 (https://doi.org/10.3892/ijo.2019.4735). Figure 8A, panels NC mimics 2 and miR-548b mimics 2 appear to have been duplicated with similar images in Figure 8A from Song et al, 2019 (https://doi.org/10.2147/OTT.S201282). The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor advised for the article to be retracted. 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”. This retraction relates to this paper

Luu X, Yue M, Li C, Sun D, Wang L. Onco Targets Ther. 2020;13:12067–12081. The Editor and Publisher of OncoTargets and Therapy wish to publish an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. The authors provided several files in response to our queries but they did not satisfy our requirements to confirm the authenticity of some types of data. In addition, there were unexplained similarities between some of the figures presented in this article, and figures presented in articles by different authors groups. As yet, the authors have not provided a satisfactory explanation for this. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Meng Yue, Shiquan Li, Guoqiang Yan, Chenyao Li, Zhenhua Kang Department of Surgery, First Hospital, JiLin University, Changchun, Jilin, People’s Republic of China Purpose: This study aimed to evaluate the short- and long-term outcomes of laparoscopic hepatectomy (LH) for colorectal liver metastases (CRLM) in elderly patients.Patients and methods: Between January 2009 and January 2016, LH was performed for 241 consecutive patients who were ≥60 years old and had CRLM. Based on their age at the LH, the patients were divided into an elderly group (≥70 years old, 78 patients) and a middle-aged group (60–69 years old, 163 patients). The short- and long-term outcomes were compared between the two groups.Results: Compared to the middle-aged group, the elderly group had higher values for Charlson comorbidity index, proportion of preoperative chemotherapy, and American Society of Anesthesiologists score. No other significant differences were observed in the preoperative characteristics. The elderly group had a higher conversion rate, compared to the middle-aged group, although no significant differences were observed in the surgical procedures, surgical times, intraoperative blood losses, numbers and severities of postoperative 90-day complications, postoperative 90-day mortality rates, pathology results, and other short-term outcomes. Long-term follow-up revealed similar rates of recurrence, disease-free survival, and overall survival in the two groups. Multivariable analysis revealed that age did not independently predict overall survival or disease-free survival.Conclusion: Similar short- and long-term outcomes were observed after LH for CRLM in elderly and middle-aged patients. Thus, advanced age is not a contraindication for LH treatment in this setting. Keywords: laparoscopic hepatectomy, minimally invasive surgery, colorectal liver metastases, surgical oncology

In recent years, MnFePGe magnetocaloric materials have been widely studied as promising candidates for magnetic refrigeration materials. The Curie temperature of MnFePGe can be adjusted to around room temperature by changing the element ratio or doping with other elements. Due to its first-order magnetic and structural transition, it engenders a large entropy change but unfortunately also exhibits a large thermal hysteresis during the phase transition, which leads to energy loss and lower refrigeration capability. In this paper, we establish a correlation between the in-plane covalent bonding and Curie temperature (TC), thermal hysteresis (ΔThys), two-phase coexistence zone (ΔTcoex), and entropy change (ΔSDSC) using 54 Mn2−xFexPyGe1−yMz (where M is a metallic or nonmetallic doped element) samples with different components. Neutron diffraction and XRD diffraction data and refinements have been employed to allow a detailed electron density reconstruction of six typical samples with the maximum entropy method. We find that the length of the in-plane bonding is closely correlated with the TC and ΔThys, while the TC, ΔThys, ΔTcoex, and ΔSDSC have no significant correlation with the length of the interlayer covalent bond. Moreover, we find that the ΔThys correlates most strongly with the change in the bond length when undergoing the paramagnetic-to-ferromagnetic phase transition rather than the absolute value of the bond length. These results provide an understanding of how to control the properties, enabling effective ways to tune the composition of magnetic refrigeration materials to tailor magnetocaloric properties for optimal performance. [ABSTRACT FROM AUTHOR]

Pei-Wen Liu,* Ming-Xia Yue,* Rui Zhou, Juan Niu, Du-Juan Huang, Tao Xu, Pei Luo, Xiao-Hong Liu, Jun-Wei Zeng Department of Physiology, Zunyi Medical College, Guizhou, China *These authors contributed equally to this work Objective: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. Dorsal horn P2Y12 and P2Y13 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known whether P2Y12 and P2Y13 receptors activation is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in cultured dorsal spinal cord microglia. For this reason, we examined the effects of ADPβs (ADP analog) on the expression and the release of IL-1β, IL-6, and TNF-α.Methods and results: In this study, we observed the effect of P2Y receptor agonist ADPβs on the expression and release of IL-1β, IL-6 and TNF-α by using real-time fluorescence quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). ADPβs induced the increased expression of Iba-1, IL-1β, IL-6 and TNF-α at the level of messenger RNA (mRNA). ADPβs-evoked increase in Iba-1, IL-1β, IL-6 and TNF-α mRNA expression was inhibited only partially by P2Y12 receptor antagonist MRS2395 or P2Y13 receptor antagonist MRS2211, respectively. Similarly, ADPβs-evoked release of IL-1β, IL-6 and TNF-α was inhibited only partially by MRS2395 or MRS2211. Furthermore, ADPβs-evoked increased expression of Iba-1, IL-1β, IL-6 and TNF-α mRNA, and release of IL-1β, IL-6 and TNF-α were nearly all blocked after co-administration of MRS2395 plus MRS2179. Further evidence indicated that P2Y12 and P2Y13 receptor-evoked increased gene expression of IL-1β, IL-6 and TNF-α were inhibited by Y-27632 (ROCK inhibitor), SB203580 (P38MAPK inhibitor) and PDTC (NF-κb inhibitor), respectively. Subsequently, P2Y12 and P2Y13 receptor-evoked release of IL-1β, IL-6 and TNF-α, were also inhibited by Y-27632, SB203580 and PDTC, respectively.Conclusion: These observations suggest that P2Y12 and P2Y13 receptor-evoked gene expression and release of IL-1β, IL-6 and TNF-α are associated with ROCK/P38MAPK/NF-κb signaling pathway. Keywords: glial activation, P2 receptor, NF-kB, p38 mitogen-activated protein kinasez

Soil-borne fungi influence coexistence of plant species in mesic environments, but much less is known about their effects on demographic processes relevant to coexistence in arid and semi-arid systems. We isolated 43 fungal strains that naturally colonize seeds of an invasive winter annual (Brassica tournefortii) in the Sonoran Desert, and evaluated the impact of 18 of them on seed germination and mortality of B. tournefortii and a co-occurring native annual (Plantago ovata) under simulated summer and winter temperatures. Fungi isolated from B. tournefortii seeds impacted germination and mortality of seeds of both plant species in vitro. Seed responses reflected host-specific effects by fungi, the degree of which differed significantly between the strains, and depended on the temperature. In the winter temperature, ten fungal strains increased or reduced seed germination, but substantial seed mortality due to fungi was not observed. Two strains increased germination of P. ovata more strongly than B. tournefortii. In the summer temperature, fungi induced both substantial seed germination and mortality, with ten strains demonstrating host-specificity. Under natural conditions, host-specific effects of fungi on seed germination may further differentiate plant species niche in germination response, with a potential of promoting coexistence. Both host-specific and non-host-specific effects of fungi on seed loss may induce polarizing effects on plant coexistence depending on the ecological context. The coexistence theory provides a clear framework to interpret these polarizing effects. Moreover, fungi pathogenic to both plant species could induce host-specific germination, which challenges the theoretical assumption of density-independent germination response. These implications from an in vitro study underscore the need to weave theoretical modeling, reductive empirical experiments, and natural observations to illuminate effects of soil-borne fungi on coexistence of annual plant species in variable desert environments.

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers. [ABSTRACT FROM AUTHOR]